Pharmacodynamics in horses refers to the study of how drugs affect the equine body, encompassing the mechanisms of action, the relationship between drug concentration and effect, and the duration of these effects. This field examines how drugs interact with biological systems in horses to produce therapeutic or adverse effects. Key aspects include receptor binding, post-receptor effects, and chemical interactions. Understanding pharmacodynamics is essential for determining appropriate dosages, predicting drug interactions, and assessing therapeutic outcomes in equine medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamic properties of various drugs in horses, focusing on their effects, efficacy, and safety profiles.
Auvinen JRE, Kritchevsky JE, Reinhart JM, Gochenauer AE, Jannasch AS, Han-Hallett Y.Manipulation of forms of rectally administered metronidazole to improve bioavailability in horses has not been reported. Objective: Evaluate the pharmacokinetics of 3 rectal metronidazole preparations compared to nasogastric (NG) administration. Methods: Seven healthy horses. Methods: Phase 1A was a randomized, 3-way crossover, single-dose pharmacokinetic study, and Phases 1B and 2 were non-randomized, single-dose follow-up studies. Metronidazole (20Â mg/kg) was administered NG and rectally in water (RW20), as a rectal gel (RG), and in dimethyl sulfoxide (DMSO). Metronidazole (80Â mg/kg) was a...
Sullivan J, Blea J, McKemie DS, Kass PH, Knych HK.The pharmacokinetics and pharmacodynamics of betamethasone following intra-articular administration to horses have been described; however, studies characterizing intramuscular administration are lacking. Twenty-four horses received an intramuscular dose of 12 mg betamethasone sodium phosphate/betamethasone acetate. Blood and urine were collected at post administration for up to 408 h. Concentrations of betamethasone were determined using LC-MS/MS and pharmacokinetic parameters determined using a Population PK three-compartment model. The duration of pharmacodynamic effects was assessed by...
Rudeekiatthamrong A, Nguyen GT, Kamyingkird K. infection (Surra) remains a major constraint to equine health and productivity in Thailand. The only available trypanocidal drug, diminazene aceturate (DA), has limited efficacy, poor blood-brain barrier penetration, and toxicity in horses. This study aimed to investigate the inhibitory effects of commonly used equine antibiotics, gentamicin (GMC), ceftiofur (CTF), and trimethoprim-sulfamethoxazole (TS), against (Thai strain isolated from dairy cattle number 953; TEDC 953) to identify potential therapeutic alternatives or adjuncts for equine trypanosomosis. Unassigned: An growth inhibition...
Sullivan J, Blea J, Morales CJ, McKemie DS, Kass PH, Knych HK.Corticosteroids, such as isoflupredone, are effective anti-inflammatory medications and as such are commonly used to treat inflammation associated with training and injuries in performance horses. While the pharmacokinetics and pharmacodynamics of isoflupredone acetate (IPA) following intra-articular administration to horses has been well described, studies characterizing intramuscular (IM) administration are lacking. The objective of the current study was to describe the pharmacokinetics and anti-inflammatory effects of IPA following IM administration to horses. Twelve horses received a singl...
Stokes C, Natalini CC, Wills R, Eddy A, Mochal-King C, O'Shea C, Fontenot RL.To evaluate the analgesic properties and adverse effects of liposomal bupivacaine administered via caudal epidural in horses. Methods: Pharmacodynamic study. Methods: A total of 10 healthy adult horses. Methods: Liposomal bupivacaine (10 mL; 1.3%) was administered into the caudal epidural space via an indwelling epidural catheter inserted to a length of 15 cm. Mechanical nociceptive threshold (MNT) testing with pressure algometry was used to measure analgesia at four anatomic locations for 72 h following injection. Physical examinations (including rectal temperature, heart rate, respirat...
Chiavaccini L, Moura RA, Azevedo TMBPR, De Gennaro C, Vettorato E, Romano M, Portela DA.Dexmedetomidine improves pulmonary function in dogs and humans, but evidence in horses is scarce. This study evaluated dexmedetomidine infusion on oxygenation and respiratory mechanics in anesthetized horses. Twenty horses undergoing elective surgery were included in a prospective, non-randomized, observational study. Horses received either lidocaine alone (1.3 mg/kg over 15 min, then 3 mg/kg/hour; LIDO) or combined with dexmedetomidine (1.75 μg/kg over 15 min, then 1.75 μg/kg/hour; DL). Respiratory mechanics, gas exchange, and cardiovascular variables were recorded at baseline, post-loading...
Thorn CA, Wilson DV, Wang S, Horne WA.Standing sedation is a safe and cost-effective alternative to general anesthesia in horses, but challenges include achieving adequate drug effect to block the stimulus response without inducing ataxia or recumbency. A benefit of midazolam has been reported in equine dental procedures. Seeking synergy, a combination of lower doses of several pharmacologic agents, including midazolam, may improve the quality of sedation while minimizing adverse effects. Bispectral index (BIS) correlates with sedation scores in human ICU patients, but the correlation between sedation scores and BIS has not been e...
Ekstrand C, Michanek P, Hernlund E, Gehring R, Spjut K, Salomonsson M.There has been a growing interest in the use of cannabinoids in horses in recent years. Several studies have reported on the pharmacokinetics of cannabidiol (CBD) in horses. However, cannabidiolic acid (CBDA) has received less attention, despite limited evidence suggesting clinically beneficial effects in other species. Horses were administered 3 mg/kg of CBD, 3 mg/kg of CBDA, and a placebo per os in a crossover design, with a one-week washout period between treatments. Plasma and urine samples were collected and analyzed using ultra high-performance liquid chromatography coupled to tandem...
Ajeebsanu MM, Koshy SA, Karakka Kal AK, Subhahar MB, Karatt TK, Philip M.Suzetrigine, a recently approved Na1.8 sodium channel blocker, shows strong potential in the treatment of neurological, psychiatric, and pain-related conditions. Its peripheral selectivity enables effective pain management while avoiding central nervous system complications and addiction risks linked to opioid use. Following FDA approval in January 2025, concerns have emerged regarding its possible misuse for performance enhancement in sports, highlighting the need for reliable detection tools in doping control. Methods: An analytical procedure was designed and validated to detect suzetrigine ...
Shimizu Y, Sugai-Bannai M, Tanabe H, Saito K, Ito H, Tokushige H, Kamiya K, Hirano-Kodaira M, Yamada M, Leung GN.Somapacitan is the second generation of recombinant human growth hormone (rhGH) medication that retains the pharmacological effects of rhGH but exhibits a longer duration of action due to its reversible albumin-binding in the body. In general, the use of all recombinant growth hormone (rGH) analogues is banned by the human and animal sports regulatory authorities due to their anabolic and lipolytic effects. However, little is known about the elimination kinetics and biological effects of the newly introduced long-acting rhGH, somapacitan, in horses. This paper describes the administration stud...
Arantes JA, Rabelo IP, Bermudes L, Lacerenza MD, Mendes RP, Corrêa RR, Yamada DI, Valadão CAA, Dória RGS.This study aimed to compare the sedation quality and cardiorespiratory and behavioral effects of detomidine administered intravenously, either in intermittent boluses or as a continuous rate infusion, with butorphanol in horses pre-medicated with acepromazine for odontoplasty procedures. Unassigned: A prospective clinical study was conducted with fifteen adult horses randomly assigned to two groups: Bolus group (BG, = 7) and Infusion group (IG, = 8). Both groups received acepromazine premedication, followed by detomidine administration (bolus or infusion). Butorphanol was administered either...
Hoh RL, Mama KR, Morales CJ, McKemie DS, Kass PH, Knych HK.To assess absorption after transdermal application of buprenorphine to different sites and assess behavioral, antinociceptive and adverse effects. It was hypothesized that the dose and site of transdermal buprenorphine administration would influence absorption, plasma drug concentrations, physiological, antinociceptive and behavioral effects in horses. Methods: Two-part study; prospective randomized balanced three-way crossover (study 1) and single-dose (study 2) experimental study. Methods: Six (study 1) and eight (study 2) horses, aged 3-14 years. Methods: In study 1, horses were administere...
Maldonado Moreno N, Alves Moreira J, Araujo De Oliveira L, Sanches Gontijo A, Castilho Baldi ML, Rocha Wenceslau R, Beier SL.A multimodal approach is recommended to optimize perioperative pain control in animals, although opioid use in horses remains limited due to the risks of central nervous system (CNS) stimulation and reduced intestinal motility. A group of 19 healthy, male, mixed-breed horses were divided into two groups and medicated with acepromazine (0.05 mg kg) and detomidine (10 µg kg), with methadone (0.05 mg kg) (ADM) or saline (ADS) administered intravenously (IV). Physiological variables, intestinal motility, gastric distention, and facial pain (EQUUS-FAP) were evaluated one day before (DB), before th...
Gomes ÉR, Felix LA, Gonzaga LWF, da Silva NFD, Soares BCF, de Almeida JVFC, Souza GP, Pereira RN, Taffarel MO, Ferrante M.The combination of detomidine and midazolam may provide safer sedation with muscle-relaxant effects, which are particularly necessary during standing procedures. Unassigned: Thus, the objective of this study was to evaluate the sedative and muscle-relaxant effects of the detomidine/midazolam combination in horses through a pharmacodynamic study. Unassigned: Five horses were used and subjected to four experimental protocols: 15 µg/kg of detomidine (D15); a combination of detomidine (15 µg/kg) with 25 µg/kg (DM25), 50 µg/kg (DM50), or 75 µg/kg (DM75) of midazolam administered intravenously....
Kuroda T, Minamijima Y, Niwa H, Mita H, Nomura M, Ohta M.A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the dosage regimens of trimethoprim/sulfamethoxazole for methicillin-resistant Staphylococcus aureus (MRSA) infections after intravenous (IV) and per os (PO) administration in horses. Methods: Trimethoprim/sulfamethoxazole plasma concentrations were measured in six horses after a single IV administration of 15 mg/kg (2.5 mg/kg trimethoprim and 12.5 mg/kg sulfamethoxazole) and PO administration of 30 mg/kg (5.0 mg/kg trimethoprim and 25.0 mg/kg sulfamethoxazole). The data were modeled using a nonlinear mixed-effects mode...
Baptiste KE, Kyvsgaard NC, Ahmed MO, Damborg P, Dowling PM.Rifampin is an enigma among antimicrobials. Blood and tissue compartment concentrations are a "moving target" along the treatment course due to the complex pharmacodynamic interactions within the body. Rifampin concomitant therapies are for the prevention and treatment of Rhodococcus equi infection in foals, for nearly 40 years. The necessity of rifampin concomitant therapies is based on beliefs that both antimicrobials (e.g., rifampin plus macrolide) penetrate into pulmonary abscesses and intracellular compartments above R. equi minimum inhibitory concentrations (MICs), as well as better ef...
Sayler B, Manship AJ, Davis J, Taylor J, Gilliam L.Chloramphenicol is a broad-spectrum antibiotic used in equine practice. It is known to produce adverse effects of hyporexia/anorexia after oral administration. Administration per rectum (PR) could mitigate the appetite suppression seen with oral administration and allow its use in horses unable to receive oral medications. The objectives of this study were to evaluate the relative bioavailability of chloramphenicol administered PR or via nasogastric tube (NGT) and determine relevant pharmacokinetic/pharmacodynamic parameters and metabolic ratios. Ten healthy, adult horses were administered chl...
Bacon EK, Donnelly CG, Finno CJ, Haase B, Velie BD.Multimodal analgesic administration is a promising strategy for mitigating side effects typically associated with analgesia; nevertheless, variation in analgesic effectiveness still poses a considerable safety concern for both horses and veterinarians. Pharmacogenomic studies have started delving into genetic influences on varying drug effectiveness and related side effects. However, current findings have narrow implications and are limited in their ability to individualize analgesic dosages in horses. Hydromorphone and detomidine were administered to a cohort of 48 horses at standardized time...
Bardhi A, Lanci A, Mannini A, Castagnetti C, Barbarossa A.Background: Although antibiotic resistance is a well-known issue in veterinary medicine, studies proposing real-time therapeutic monitoring (TDM) are lacking. The objective of the present study was to develop a simple and rapid protocol for the real-time therapeutic monitoring of antibiotics in horses and dogs. Methods: A reliable TDM protocol should encompass guidelines for the definition of plasma/serum collection time points, sample management by the clinical staff, transportation to the laboratory, and the availability of robust and swift analytical technologies. Ampicillin and sulbactam w...
Kazama T, Hector RC, Hess AM, Rezende ML.To determine the cardiopulmonary effects of oral trazodone before isoflurane anesthesia in systemically healthy horses. Unassigned: 12 horses donated for euthanasia (from August 2022 through June 2023) due to conditions unrelated to the cardiovascular system were included in this prospective, randomized, controlled trial. Horses were assigned to receive oral trazodone (6 mg/kg; n = 7) or corn syrup (n = 5) 1 hour before xylazine (1 mg/kg, IV) sedation, ketamine (2.2 mg/kg, IV) and propofol (0.7 mg/kg, IV) induction, and anesthetic maintenance with inhaled isoflurane (target 1.6% expired) for 7...
Gao T, Liu X, Qiu D, Li Y, Qiu Z, Qi J, Li S, Guo X, Zhang Y, Wang Z, Gao X, Ma Y, Ma T.Cefquinome is used to treat septicemia caused by () and respiratory infections caused by subsp. in foals. However, studies reporting the use of cefquinome to target as pathogens of sepsis are lacking. Therefore, this study aimed to determine the optimal dosage regimen for cefquinome against using a PK/PD model. After the administration of 1 mg/kg cefquinome (intramuscularly or intravenously), blood samples were collected at different time points to determine the serum concentration of cefquinome via HPLC. The pharmacokinetic parameters were evaluated via NCA (WinNonlin 5.2.1 software). Th...
Oyaneder L, Lagos N, Dörner C.The present study was conducted to evaluate the safety and the long-lasting anesthetic properties of Neosaxitoxin (NeoSTX) when injected into the intercoccygeal space in standing horses. A group of eighteen (n = 18) healthy client-owned mature crossbreed horses were enrolled in this study. Caudal epidural injection was ascertained by two methods, the "hanging drop" technique and radiographs. Horses were allocated into three groups (n = 6) each group receiving different dosages of NeoSTX. To assess the onset of action and duration of anesthesia, six horses received 20 μg in 2 mL, six 20Â...
Júnior GS, de Souza JV, de Souza Ferreira W, Florentino VRD, Valente TC, Comassetto F, Oleskovicz N.This study aimed to evaluate the sedation degree, cardiopulmonary effects, and detomidine-sparing during dental occlusal adjustment in standing horses using a bolus and constant rate infusion (CRI) of detomidine alone or in combination with butorphanol or methadone. In this randomized, blinded clinical trial, 24 healthy adult horses were assigned to the detomidine (DT), detomidine-butorphanol (DB), or detomidine-methadone (DM) group. DT received an intravenous bolus of detomidine (20 μg/kg), followed by CRI at 20 μg/kg/h. DB received detomidine (10 μg/kg) and butorphanol (0.02 mg/kg) boluse...
Adler DMT, Nielsen AT, Olsen C, Verwilghen D, Damborg P, Olsen RH.To investigate the in vitro efficacy of antibiotics (amikacin, ceftiofur, and gentamicin) in combination with local anesthetics (LAs; bupivacaine hydrochloride, lidocaine hydrochloride, and mepivacaine hydrochloride), a combination commonly performed for IA injectate and regional limb perfusion (RLP) in horses. Unassigned: 17 equine clinical isolates were tested by the checkerboard method for their minimum inhibitory concentration (MIC) against a combination of concentrations of LAs and antibiotics from August 2020 through December 2023. Unassigned: For the majority of combinations, the antibi...
Guzmán JFC, Gontijo AS, Melgaço ES, Faria SA, Baldi MLC, Sousa LN, Wenceslau RR, Fantini P, Xavier ABDS, Beier SL.Morphine has significant clinical and analgesic effects in horses, but its impact on the gastrointestinal tract requires further understanding. This study assessed the analgesic and gastrointestinal effects of morphine in horses undergoing elective orchiectomy in the quadrupedal position. Thirty uncastrated male horses were randomly assigned to three groups: orchiectomy without morphine and sedation protocol (OSM), orchiectomy with morphine and sedation protocol (OM), and administration of morphine alone in the absence of orchiectomy (M). The anesthetic protocol involved acepromazine (0.05 mg/...
Knych HK.Pharmacokinetics is the study of the movement of drug in the body and includes the processes of absorption, distribution, metabolism, and excretion. Pharmacodynamics is the pharmacologic effect of the drug on the body. The pharmacokinetics of a drug determines its pharmacologic effect. Pharmacokinetic studies describe drug concentrations while pharmacodynamics allow for assessment of drug effects. Combined pharmacokinetic/pharmacodynamic studies allow for integration of drug concentrations with pharmacologic effect. Data generated from pharmacokinetic studies can be especially useful in establ...
Ikeda Y, Kuroda T, Mita H, Tamura N, Ohta M.We compared the antihistamine effect of four new antihistamines with olopatadine, which is used to treat equine allergic diseases. Six healthy Thoroughbred horses received oral doses of olopatadine (50 mg), levocetirizine (50 mg), bilastine (200 mg), rupatadine (100 mg), and desloratadine (50 mg) at >2-week intervals. The effects were investigated by measurement of the wheal area induced by histamine intradermal injection, and inhibition rate was compared with positive and negative controls. The maximum wheal inhibition rate (mean ± SD) of olopatadine (85.3% ± 7.7%) was significantly higher ...
Shroff K, Stefanovski D, Reef VB, Kraus MS, Solis CN.Information about congestive heart failure (CHF) treatment in the horse is limited. Torsemide, an oral loop diuretic, is increasingly used in humans, dogs, and cats with CHF. Torsemide is well absorbed and induces diuresis in healthy horses, and its use in a horse with CHF has been reported. This retrospective descriptive study aimed to describe the use of torsemide in equids with CHF. Methods: 12 equids (10 horses, 1 miniature donkey, and 1 mule). Methods: Horses presented to a referral practice with clinical signs of congestive heart failure. Diagnosis was confirmed with echocardiography. Tr...
Lees P, Landoni MF, Giraudel J, Toutain PL.This review summarises selected aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of nonsteroidal anti-inflammatory drugs (NSAIDs). It is not intended to be comprehensive, in that it covers neither minor species nor several important aspects of NSAID PD. The limited objective of the review is to summarise those aspects of NSAID PK and PD, which are important to an understanding of PK-PD integration and PK-PD modelling (the subject of the next review in this issue). The general features of NSAID PK are: usually good bioavailability from oral, intramuscular and subcutaneous administ...
Whittle BJ, Moncada S, Vane JR.The activity of prostacyclin (PGI2), PGE1 or PGD2 as inhibitors of platelet aggregation in plasma from human, dog, rabbit, rat, sheep and horse was investigated. Prostacyclin was the most potent inhibitor in all species. PGD2 was a weak inhibitor in dog, rabbit and rat plasma whereas PGE1 and prostacyclin were highly active. Theophylline or dipyridamole potentiated the inhibition of human platelet aggregation by prostacyclin, PGE1 or PGD2. Compound N-0164 abolished the inhibition by PGD2 of human platelet aggregation but did not inhibit the effects of PGE1 or prostacyclin. The results suggest ...
Afable MG, Shaik M, Sugimoto Y, Elson P, Clemente M, Makishima H, Sekeres MA, Lichtin A, Advani A, Kalaycio M, Tiu RV, O'Keefe CL, Maciejewski JP.A combination of horse anti-thymocyte globulin and cyclosporine produces responses in 60-70% of patients with severe aplastic anemia. We performed a phase II study of rabbit anti-thymocyte globulin and cyclosporine as first-line therapy for severe aplastic anemia. Methods: Twenty patients with severe aplastic anemia treated with rabbit anti-thymocyte globulin were compared to 67 historical control cases with matched clinical characteristics treated with horse anti-thymocyte globulin. Results: Response rates at 3, 6 and 12 months were similar for patients treated with rabbit anti-thymocyte glob...
Harder A, Schmitt-Wrede HP, Krücken J, Marinovski P, Wunderlich F, Willson J, Amliwala K, Holden-Dye L, Walker R.There are three major classes of anthelmintics for veterinary use: the benzimidazoles/prebenzimidazoles, the tetrahydropyrimidines/imidazothiazoles, and the macrocyclic lactones. In nematodes, there are five targets for the existing anthelmintics: the nicotinergic acetylcholine receptor which is the target of tetrahydropyrimidines/imidazothiazoles and indirectly that of the acetylcholineesterase inhibitors; the GABA receptor which is the target of piperazine, the glutamate-gated chloride channel as the target of the macrocyclic lactones, and beta-tubulin as the target of prebenzimidazoles/benz...
DrugCentral monitors new drug approvals and standardizes drug information. The current update contains 285 drugs (131 for human use). New additions include: (i) the integration of veterinary drugs (154 for animal use only), (ii) the addition of 66 documented off-label uses and iii) the identification of adverse drug events from pharmacovigilance data for pediatric and geriatric patients. Additional enhancements include chemical substructure searching using SMILES and 'Target Cards' based on UniProt accession codes. Statistics of interests include the following: (i) 60% of the covered drugs are...
England GC, Clarke KW.In recent years the usefulness of the alpha 2 adrenoceptor agonist drugs has been recognized in equine practice. Several agents have become available and are now licensed for use in a number of countries. The principle actions of all alpha 2 adrenoceptor agonists are similar, in that they produce a reduction in heart rate and alteration of heart rhythm, an initial hypertension followed by a prolonged hypotension, a decrease in the cardiac output and respiratory depression. For clinical purposes, these agents produce sedation and analgesia, they are useful for premedication and markedly potenti...
Toutain PL, Cester CC.To determine pharmacokinetic-pharmacodynamic (PK-PD) relationships and dose effects for meloxicam in horses and to propose a suitable dosage for use in clinical studies. Methods: 6 adult horses. Methods: The study was conducted by use of a randomized, Latin-square design. Arthritis was induced in the right carpal joint of each horse by administration of Freund's complete adjuvant. Various dosages of meloxicam (0, 0.25, 0.5, 1.0, and 2.0 mg/kg, IV) were then administered. Validated endpoints including stride length and overall clinical lameness score (scale of 0 to 20) were used to assess the e...
Oyarzun-Ampuero F, Vidal A, Concha M, Morales J, Orellana S, Moreno-Villoslada I.The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticles, have shown potential therapeutic effects on wound healing. Due to their specific characteristics, nanoparticles such as nanocapsules, polymersomes, solid lipid nanoparticles, and polymeric nanocomplexes are ideal vehicles to improve the effect of drugs (antibiotics, growth fact...
Wagner AE, Muir WW, Hinchcliff KW.The cardiovascular effects of xylazine and detomidine in horses were studied. Six horses were given each of the following 5 treatments, at 1-week intervals: xylazine, 1.1 mg/kg, IV; xylazine, 2.2 mg/kg, IM; detomidine, 0.01 mg/kg, IV; detomidine, 0.02 mg/kg, IV; and detomidine, 0.04 mg/kg, IM. All treatments resulted in significantly decreased heart rate, increased incidence of atrioventricular block, and decreased cardiac output and cardiac index; cardiac output and cardiac index were lowest following IV administration of 0.02 mg of detomidine/kg. Mean arterial pressure was significantly redu...
Janssen IJ, Krücken J, Demeler J, von Samson-Himmelstjerna G.P-glycoproteins (Pgps) are suspected to mediate drug extrusion in nematodes contributing to macrocyclic lactone resistance. This association was recently shown for Parascaris Pgp-11. Ivermectin resistance was correlated with the presence of three pgp-11 single nucleotide polymorphisms and/or increased pgp-11 mRNA levels. In the present study, the ability of Pgp-11 to modulate ivermectin susceptibility was investigated by its expression in a pgp-11-deficient Caenorhabditis elegans strain. Expression of Parascaris pgp-11 in two transgenic lines significantly decreased ivermectin susceptibility i...
Kleinheinz J, Jung S, Wermker K, Fischer C, Joos U.Current approaches in bone regeneration combine osteoconductive scaffolds with bioactive cytokines like BMP or VEGF. The idea of our in-vitro trial was to apply VEGF165 in gradient concentrations to an equine collagen carrier and to study pharmacological and morphological characteristics of the complex in a circulation model. Methods: Release kinetics of VEGF165 complexed in different quantities in a collagen matrix were determined in a circulation model by quantifying protein concentration with ELISA over a period of 5 days. The structural changes of the collagen matrix were assessed with lig...
Stock ML, Elazab ST, Hsu WH.Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated other protozoal diseases such as neosporosis and toxoplasmosis. In this article, we discuss the pharmacological characteristics of five triazines, toltrazuril, ponazuril, clazuril, diclazuril, and nitromezuril which are used in veterinary medicine to control protozoal diseases which include coccidiosis, equine protozoal myeloencephalitis, neosporosis, and toxoplasmosis.
Neuder LE, Keener JM, Eckert RE, Trujillo JC, Jones SL.Endotoxemia occurs when bacterial lipopolysaccharide (LPS) in the blood induces a dysregulated inflammatory response, resulting in circulatory shock and multi-organ failure. Laminitis is a common complication in endotoxemic horses and is frequently the reason for humane euthanasia of these cases. Blood leukocytes are a principal target of LPS in endotoxemia leading to activation of multiple signal transduction pathways involved in the induction of a number of pro-inflammatory genes. In other animal models, the p38 mitogen activated protein kinase (MAPK) pathway has been associated with induced...
Lyons ET, Tolliver SC, Ionita M, Lewellen A, Collins SS.Field studies (n=6) were completed on evaluation of activity of ivermectin (200 microg/kg) paste formulation against small strongyles in horses (foals, yearlings, and older animals) on a farm (Farm MC) in Central Kentucky in late 2006 and during 2007. A girth tape was used to estimate body weights which were then used to calculate the proper dose rate of ivermectin. The foals, yearlings, and some of the older horses were born and raised on the farm. However, most of the older horses which were not raised on the farm had been there for several years. The horse herd was given ivermectin exclusiv...
Ikeda T.Ivermectin is an oral semi-synthetic lactone anthelmintic agent derived from avermectins isolated from fermentation products of Streptomyces avermitilis. Ivermectin showed a concentration-dependent inhibitory effect on motility of a free-living nematode, Caenorhabditis elegans (C. elegans). There exist specific binding sites having a high affinity for ivermectin in the membrane fraction of C. elegans, and a strong positive correlation was detected between the affinity for these binding sites and the suppressive effect on motility of C. elegans in several ivermectin-related substances. These re...
Giguère S, Lee EA, Guldbech KM, Berghaus LJ.There are no studies investigating interactions between clarithromycin or azithromycin and rifampin or other commonly used antimicrobial agents against virulent isolates of Rhodococcus equi. In addition, there is no published data on the postantibiotic effects (PAEs) and pharmacodynamics properties of antimicrobial agents against R. equi. The objectives were to assess in vitro interactions, pharmacodynamics, and PAEs of 11 antimicrobial agents belonging to various antimicrobial classes against R. equi. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, ami...
Paddleford RR, Harvey RC.The alpha 2 agonists can produce reliable dose-dependent sedation and analgesia in most species. Nevertheless, they can also produce significant physiological adverse side effects depending on dose, rate, route of administration, and the concurrent use of other CNS depressants. For this reason, it may be best to use a low dose of an alpha 2 agonist as a preanesthetic agent. The alpha 2 agonists are best suited for young, healthy, exercise-tolerant patients. The combining of low doses of alpha 2, opioid, and benzodiazepine agonists results in a synergistic CNS depressant response while minimizi...
Cobb R, Boeckh A.This article reviews the current knowledge of the use of moxidectin (MOX) in horses, including its mode of action, pharmacokinetic and pharmacodynamic properties, efficacy, safety and resistance profile.Moxidectin is a second generation macrocyclic lactone (ML) with potent endectocide activity. It is used for parasite control in horses in an oral gel formulation. The principal mode of action of MOX and of other MLs is binding to gamma-aminobutyric (GABA) and glutamate-gated chloride channels. Moxidectin is different from other MLs in that it is a poor substrate for P-glycoproteins (P-gps) and ...
Toutain PL, Autefage A, Legrand C, Alvinerie M.The purpose of the present study was to establish in the horse the relationship between plasma concentration profiles of phenylbutazone (PBZ) and flunixin meglumine (FM) and their pharmacological effects in order to build a predictive pharmacokinetic/pharmacodynamic (PK/PD) model. In five horses, an experimental arthritis was induced by injecting Freund's adjuvant into a carpal joint. PBZ (4 mg/kg) and FM (1 mg/kg) were injected by the intravenous route as a single intravenous dose in two different trials. Five pharmacodynamic end-points were regularly measured after test article injection usi...
Clutton RE.Opioid analgesics have been the foundation of human pain management for centuries, and their value in animals has increased since it was proposed that it is the veterinarian's duty to alleviate pain whenever it may occur. Compared with other domesticated species, the horse has benefitted less from the increased understanding of opioid pharmacology in animals, because early literature was overlooked and later work, which examined adverse side effects rather than analgesia, concluded that analgesic and excitatory doses were irreconcilably close. More recent studies have indicated a widening role...
Garcia-Villar R, Toutain PL, Alvinerie M, Ruckebusch Y.The pharmacokinetic disposition of xylazine hydrochloride is described after both intravenous and intramuscular injection of a single dose, in four domestic species: horse, cattle, sheep and dog, by an original high performance liquid chromatographic technique. Remarkably small interspecific differences are reported. After intravenous administration, systemic half-life (t1/2 beta) ranged between 22 min (sheep) and 50 min (horse) while the distribution phase is transient with half-life (t1/2 alpha) ranging from 1.2 min (cattle) to 5.9 min (horse). The peak level of drug concentration in the pla...
Gokbulut C, McKellar QA.Internal parasites of horses comprise an intractable problem conferring disease, production and performance losses. Parasitism can rarely be controlled in grazing horses by management alone and anthelmintic drugs have formed the basis of therapy and prophylaxis for the last sixty years. The pharmacology of the anthelmintic drugs available dictate their spectrum of activity and degree of efficacy, their optimal routes of administration and characteristics which prevent some routes of administration, their safety tolerance and potential toxicities and as a consequence of their persistence in the...
Struff WG, Sprotte G.Mammals supply their newborn before birth, at birth or shortly after birth with antibodies, immunocytes and humoral constituents. This "borrowed immunity" is a form of passive immunization to protect the newborn against environmental pathogens until it establishes its own pathogen recognition and disposal systems. In cows, goats, horses and some other animal species, most immunoglobulins are obtained from the colostrum, the first milk after birth, via the gut but in humans the majority of immunoglobulins, and those of the IgG-class in particular, are acquired from the mother by placental trans...
Sangster NC.Anthelmintic-resistance has emerged as a problem in several animal industries. In the horse, cyathostome resistance to all available treatments except for the avermectin/milbemycins means that these drugs provide the cornerstone of control. Ivermectin has been available for several years; the related compound moxidectin is more recent. Although we do not know for sure, aspects of moxidectin such as its persistent action and its efficacy against mucosal stages of cyathostomes, may enhance the rate of development of resistance. On the other hand, selection pressure would be reduced if the persis...
Marshall JF, Blikslager AT.Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the management of pain and endotoxaemia associated with colic in the horse. While NSAIDs effectively treat the symptoms of colic, there is evidence to suggest that their administration is associated with adverse gastrointestinal effects including right dorsal colitis and inhibition of mucosal barrier healing. Several studies have examined the pathophysiology of NSAID associated effects on the large and small intestine in an effort to avoid these complications and identify effective alternative medications. Differences in the re...
de Grauw JC, van de Lest CH, van Weeren PR.Articular tissues are capable of producing a range of eicosanoid mediators, each of which has individual biological effects and may be affected by anti-inflammatory treatment. We set out to develop and evaluate a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) approach for the simultaneous analysis of multiple eicosanoid lipid mediators in equine synovial fluid (SF), and to illustrate its use for investigation of the in vivo effects of non-steroidal anti-inflammatory drug (NSAID) treatment. Methods: Synovial fluid samples were obtained from normal joints of 6 adult...
Fenner MF, Carstensen H, Dalgas Nissen S, Melis Hesselkilde E, Scott Lunddahl C, Adler Hess Jensen M, Loft-Andersen AV, Sattler SM, Platonov P....Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF. The pharmacological ion channel profile of XAF-1407 was investigated us...
