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.
Kerr DD, Jones EW, Holbert D, Huggins K.A 3-way Latin square design was used to compare the sedative and preanesthetic effects of xylazine given intravenously (i.v.) (1.1 mg./kg.) and given intramuscularly (i.m.) (2.2 mg./kg.) and acetylpromazine maleate (0.66 mg./kg.) given i.v. in the horse. Physiologic responses were recorded and clinical observations were made. Intravenous administration of xylazine and atropine sulphate (0.011 mg./kg.) appeared to have superior sedative properties, without having adverse effects on cardiovascular and respiratory systems. Both the i.v. and the i.m. administrations of xylazine prior to induction ...
Lees P, Tavernor WD.1. Ventricular ectopic beats were recorded in eight of thirteen conscious horses following the intravenous administration of adrenaline in doses of 3 mug/kg. Following pre-treatment with either atropine sulphate (0.1 mg/kg) or propranolol hydrochloride (0.1 mg/kg), the same dose level of adrenaline failed to produce ventricular ectopic beats.2. Halothane anaesthesia sensitized the equine heart to the arrhythmogenic actions of adrenaline; the incidence and duration of ventricular arrhythmias being greater than in conscious animals. In comparison with the findings in conscious horses, ether anae...
Lees P, Tavernor WD.1. In horses anaesthetized with halothane the intravenous administration of suxamethonium chloride, at a dose level of 0.2 mg/kg, produced a short-lived period of hypoventilation, which was associated with increases in arterial blood PCO(2) levels and in plasma concentrations of bicarbonate, sodium and potassium ions, and reductions in arterial blood pH and PO(2) values.2. The respiratory depressant action of suxamethonium chloride 0.2 mg/kg was accompanied by increases in blood pressure and heart rate. Doses of suxamethonium chloride 0.4 mg/kg produced similar but quantitatively greater chang...
Knych HK, Stanley SD, McKemie DS, Steinmetz SJ.Romifidine is an alpha-2 adrenergic agonist used for sedation and analgesia in horses. As it is a prohibited substance, its purported use at low doses in performance horses necessitates further study. The primary goal of the study reported here was to describe the serum concentrations and pharmacokinetics of romifidine following low-dose administration immediately prior to exercise, utilizing a highly sensitive liquid chromatography-tandem mass spectrometry assay that is currently employed in many drug testing laboratories. An additional objective was to describe changes in heart rate and rhyt...
Abutarbush SM, Alfaqeeh SM, Mustafa G, Qura'n L, Al-Majali AM.To evaluate the ability of atropine sulfate, butylscopolammonium bromide combined with metamizole sodium, and flunixin meglumine to ameliorate the clinical adverse effects of imidocarb dipropionate in horses. Methods: 28 horses with piroplasmosis. Methods: 28 horses were randomly assigned to 4 equal groups according to the pretreatment administered. Fifteen minutes before administration of 2.4 mg of imidocarb dipropionate/kg IM, horses in the first group were pretreated with 0.02 mg of atropine sulfate/kg IV, the second group with a combination of 0.2 mg of butylscopolammonium bromide/kg IV an...
Ebner L, O O, Simon B, Lizarraga I, Smith J, Cox S.The pharmacokinetics of butorphanol after intravenous (IVB) and intramuscular (IMB) administration in donkeys were determined in this preliminary study. Healthy male gelded donkeys ( = 5), aged 6-12 years old, were administered 0.1 mg/kg butorphanol IV or IM in a randomized, crossover design. Blood samples were obtained at predetermined intervals for 24 h (IVB) and 48 h (IMB) after administration. Plasma butorphanol concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters were calculated. Following IVB administration, mean (± SE) apparent volume ...
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...
Auer U, Uray C, Mosing M.To investigate the onset and duration of neuromuscular blockade of rocuronium bromide and its associated haemodynamic effects at three doses in healthy horses. Methods: Prospective, randomized experimental study. Methods: Seven adult horses aged 3-20 (mean 10.3) years and weighing 466 +/- 44 (mean +/- SD) kg. Methods: Horses were anaesthetized three times with at least 2 weeks between. They were pre-medicated with 0.6 mg kg(-1) xylazine and 0.01 mg kg(-1) butorphanol i.v.. Anaesthesia was induced with 2.2 mg kg(-1) ketamine and 0.1 mg kg(-1) diazepam i.v.. Following orotracheal intubation anae...
Bochsler PN, Slauson DO, Neilsen NR.The essential role of the CD11/CD18 family of leukocyte adhesion molecules (LeuCams) in neutrophil-substrate adhesion is well documented. We have found that a monoclonal antibody designated 60.3 (MoAb 60.3) that recognizes the common beta-subunit (CD18) on human neutrophils (PMN) also recognizes a surface antigen on equine PMN. Antigen expression as assessed by immunofluorescence flow cytometry was enhanced by zymosan-activated serum (ZAS) or phorbol 12-myristate 13-acetate (PMA) stimulation. Pretreatment of equine PMN with MoAb 60.3 inhibited ZAS-stimulated aggregation, indicating that the mo...
White DA, Hildebrand SV, Jones JH, Fung DL, Gronert GA.On the basis of results in dogs, conditioning exercise may increase sensitivity to nondepolarizing muscle relaxants. Five Thoroughbreds were exercised/conditioned 3 times weekly on a treadmill for 8 months. Increasing maximal rate of O2 consumption verified that the horses were responding to exercise conditioning. Six nonexercised Thoroughbreds served as the control group. Studies were done with horses under general anesthesia by use of halothane during partial paralysis by a brief constant-rate infusion with the muscle relaxant, metocurine iodide. Quantification of degree of paralysis of the ...
Epstein KL, Bergren A, Nie B, Arnold RD, Brainard BM.A lower molecular weight and molar substitution formulation (130/0.4) of hydroxyethyl starch solution has been shown to have a more sustained effect on COP and similar hemodynamic effects as a higher molecular weight and molar substitution formulation (600/0.75) in healthy horses. In humans, these pharmacodynamic characteristics are coupled with more rapid clearance and decreased adverse coagulation effects and accumulation. The objective of this study was to determine and compare the pharmacokinetics of these two formulations in horses. Eight healthy horses were given a 10 mL/kg bolus of eac...
Turkan F, Harbi Calimli M, Akgun A, Gulbagca F, Sen F.Benzimidazoles are antiparasitic drugs having an extensive application field like agriculture, medicine, and especially in veterinary medicine. In this study, we report the effect of some benzimidazole drugs such as ricobendazole (RBZ), thiabendazole (TBZ), albendazole (ALBA) and oxfendazole (OFZ) on glutathione s-transferase (GST) enzyme activity. The kinetics studies, IC and Ki values of the tested drugs on GSTs enzyme activity were investigated. The obtained ranking of IC values were found to be approximately RBZ (53.31 μM, r 0.9778) < OFZ (57.75 μM, r 0.9630) < ALBA (63.00 μM, r 0...
Lees P, Toutain PL.The presence of horse meat in food products destined for human consumption and labelled as beef has raised several concerns of public interest. This review deals solely with one aspect of these concerns; samples of equine tissue from horses destined for the human food chain have tested positive for the non-steroidal anti-inflammatory drug, phenylbutazone. The safety of some or all such foods for human consumers is a major concern, because it was shown many years ago that phenylbutazone therapy in humans can be associated with life threatening blood dyscrasias. As an initial basis for assessing...
Törneke K, Ingvast-Larsson C, Pettersson K, Bergvall K, Hedeland M, Bondesson U, Broström H.Clemastine is an H1 antagonist used in certain allergic disorders in humans and tentatively also in horses, although the pharmacology of the drug in this species has not yet been investigated. In the present study we determined basic pharmacokinetic parameters and compared the effect of the drug measured as inhibition of histamine-induced cutaneous wheal formation in six horses. The most prominent feature of drug disposition after intravenous dose of 50 microg/kg bw was a very rapid initial decline in plasma concentration, followed by a terminal phase with a half-life of 5.4 h. The volume of d...
McReynolds CB, Yang J, Guedes A, Morisseau C, Garcia R, Knych H, Tearney C, Hamamoto B, Hwang SH, Wagner K, Hammock BD.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...
Berryhill EH, Knych H, Chigerwe M, Edman J, Magdesian KG.The neurokinin-1 (NK-1) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood in horses, and clinical use of NK-1 receptor antagonists has not been reported. This study aimed to determine the pharmacokinetics and safety of maropitant after administration of multiple doses. We hypothesized that maropitant concentrations would be similar at steady state to those reported in dogs, with minimal adverse effects. Maropitant was administered at 4 mg/kg orally, once daily for 5 days in seven adult horses. Serial plasma maropitant concent...
Knych HK, Stanley SD.To describe the effects of alpha2 -adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse. Methods: Randomized crossover design. Methods: Nine healthy adult horses with an average age of 7.6 ± 6.5 years. Methods: Four treatment groups were studied: 1) 0.04 mg kg(-1) detomidine SL; 2) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.075 mg kg(-1) yohimbine intravenously (IV); 3) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 4 mg kg(-1) tolazoline IV; and 4) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.12 m...
Combie J, Shults T, Nugent EC, Dougherty J, Tobin T.The locomotor responses of horses given morphine and fentanyl were blocked or lessened by administration of naloxone or acepromazine. Naloxone given at the dosage of 0.015 mg/kg completely blocked the locomotor activity induced in horses given fentanyl (0.020 mg/kg of body weight). The locomotor stimulation produced by morphine given at the dosage of 2.4 mg/kg was reduced by 75% of naloxone (0.020 mg/kg). Acepromazine partially blocked the locomotor responses to fentanyl and morphine. This blockade activity reached its peak about 30 minutes after acepromazine was given (IV) and lasted more tha...
Pascoe PJ, Black WD, Steffey EP.We measured plasma concentrations of alfentanil in two horses after three different randomly ordered treatments. Each horse received halothane in oxygen by mask followed by a bolus dose of alfentanil 60 micrograms kg-1 i.v., halothane in oxygen by mask followed by an i.v. alfentanil infusion for 120 min and xylazine and ketamine followed by halothane and a bolus dose of alfentanil 60 micrograms kg-1 i.v. Halothane was maintained at 1.05-1.07% end-tidal concentration with a PaCO2 of 6-7.3 kPa. The plasma concentration-time curves were similar after bolus and infusion doses of alfentanil with ha...
Boye JK, Katzman SA, Kass PH, Dujovne GA.In equids, it is common to inject lidocaine into the testicles at the time of routine castration to provide analgesia. The effects of lidocaine on equine sperm have not been evaluated in vitro or on epididymal sperm collected following castration. The aims of this study were to determine effects of clinically relevant doses of lidocaine on equine spermatozoa in vitro using freshly collected semen and to compare the characteristics of epididymal spermatozoa after routine castration with or without intra-testicular lidocaine administration. We hypothesized that increasing concentrations of lid...
Ellerbrock RE, Curcio BR, Zhong L, Honoroto J, Wilkins P, Lima FS, Giguere S, Canisso IF.Enrofloxacin may be an alternative antimicrobial for unresponsive cases of severe bacterial infections in pregnant mares. As pregnancy may affect drug bioavailability, distribution, metabolism and excretion, dose adjustment might be necessary. Objective: To determine the disposition of orally and intravenously administered enrofloxacin in pregnant and non-pregnant mares. Methods: Randomised cross-over experiment. Methods: Six light-breed, healthy pregnant mares (260 days gestation) were given a single dose of either intravenous (5 mg/kg bwt) or oral compounded (7.5 mg/kg bwt) enrofloxacin, ...
Brimijoin S, Mintz KP, Prendergast FG.Interactions between dansylarginine N-(3-ethyl-1,5-pentanediyl)amide (DAPA) and the cholinesterases were examined by the techniques of enzyme kinetics and fluorescence spectroscopy. When tested with partially purified enzyme preparations, DAPA was a potent inhibitor of butyrylcholinesterase (IC50 = 2 x 10(-7) M) but not of acetylcholinesterase (IC50 = 4 x 10(-4) M). For a detailed study of the effects of DAPA on butyrylcholinesterase (BuChE), the enzyme was purified to homogeneity from horse serum, with the aid of affinity chromatography on N-methyl acridinium. The kinetics of the inhibition o...
Knych HK, Weiner D, Harrison L, McKemie DS.Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. S...
Coyne CP, Smith JE, Keeton K.A selected group of pharmaceutical compounds were evaluated for the ability to inhibit the biochemical activity of fibrinoligase (coagulation factor XIIIa*) in pooled equine plasma. Criteria for the pharmaceuticals selected were based on the mechanism of the transglutamination biochemical reaction mediated by coagulation factor XIIa*. These criteria were complemented by recognition of the molecular configuration and chemical composition of amino acid residue side chains involved in the process of covalent fibrin monomer polymerization (cross-linking, transglutamination) mediated by this enzyme...
Coakley M, Peck KE, Taylor TS, Matthews NS, Mealey KL.To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. Methods: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. Methods: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumi...
Auckburally A, Wiklund M, Lord P, Nyman G.To measure changes in regional lung perfusion using CT angiography in mechanically ventilated, anesthetized ponies administered pulsed inhaled nitric oxide (PiNO) during hypotension and normotension. Methods: 6 ponies for anesthetic 1 and 5 ponies for anesthetic 2. Methods: Ponies were anesthetized on 2 separate occasions, mechanically ventilated, and placed in dorsal recumbency within the CT gantry. Pulmonary arterial, right atrial, and facial arterial catheters were placed. During both anesthetics, PiNO was delivered for 60 minutes and then discontinued. Anesthetic 1: hypotension (mean arter...
King JN, Gerring EL.Post operative ileus is a serious complication of abdominal surgery in horses and there is evidence that endotoxin plays a significant role in its pathogenesis. Pre-treatment with intravenous (i.v.) flunixin (1.1 mg/kg bodyweight [bwt]) or phenylbutazone (4.4 mg/kg bwt) significantly antagonised the acute disruption of gastric, small intestinal and large intestinal motility induced by 0.1 microgram/kg bwt i.v. endotoxin in ponies implanted with gastrointestinal strain gauges. Phenylbutazone was more effective than flunixin and this was significant (P < 0.01) for the stomach and left dorsal col...
Muir WW.The cardiovascular effects of serial increasing infusions of dopexamine HCl were investigated in six conscious (1, 2, 4, 6, 10 micrograms/kg bodyweight [bwt]/min) and eight (0.5, 1, 5, 10, 20 micrograms/kg bwt/min) halothane-anaesthetised horses. Dopexamine produced dose-dependent increases in heart rate, +dP/dtmax' -dP/dtmax and cardiac output, and a decrease in systemic vascular resistance in conscious and halothane-anaesthetised horses. Mean arterial blood pressure did not change in conscious horses but increased to a maximum value at 10 micrograms/kg bwt/min in halothane-anaesthetised hors...
Heath MF, Evans RJ, Poole AW, Hayes LJ, McEvoy RJ, Littler RM.The responses of equine blood platelets in citrated platelet-rich plasma to arachidonic acid, U44069 (prostaglandin endoperoxide analogue), adenosine 5'-diphosphate, platelet-activating factor or collagen were investigated by turbidimetric aggregometry. Pre-treatment of the platelets with aspirin (1 mmol/l) or paracetamol (1.3 mmol/l) abolished shape change and aggregation in response to arachidonic acid; decreased the rate of aggregation in response to collagen, with no separate effect on shape change; had no marked effect on aggregation caused by the other agonists; but in no case transforme...
Aviad AD, Houpt JB.Various molecular weight hyaluronic acid (HA) preparations have been injected into joints for the treatment of human and equine osteoarthritis. A therapeutic advantage has been claimed for commercial products with a molecular weight in the range found in normal synovial fluid (SF), compared to lower molecular weight products. But a correlation between molecular weight and efficacy is not borne out by an analysis of the available literature on clinical results. SF viscosity, HA concentration, HA molecular weight and rate of synthesis in joint disease. It is proposed that the beneficial effect o...
Olson LE, Perkowski SZ, Mason DE, Muir WW.Strips of trachealis muscle were dissected from the midcervical portion of the trachea of horses that were free of respiratory tract disease, and the overlying epithelium and mucosa were removed. Muscle strips were suspended in tissue baths that were filled with Krebs-bicarbonate solution, aerated with 5% CO2 in oxygen and maintained at 37 C. Isometric tension was continuously recorded. The increase in active isometric tension was concentration dependent when acetylcholine (10(-9) to 10(-4) M) or histamine (10(-9) to 10(-4) M) was added to the tissue baths in 0.5-logarithmic increments. When t...
Rendle DI, Hughes KJ, Doran GS, Edwards SH.To determine the pharmacokinetics of pergolide after IV administration to horses. Methods: 8 healthy adult horses. Methods: Pergolide mesylate was administered IV at a dose of 20 μg/kg (equivalent to 15.2 μg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods. Results: After IV administration of pergolide, mean ± SD clearance, elimination half-life, a...
Whittem T, Firth EC, Hodge H, Turner K.This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone...
