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.
Trachsel D, Tschudi P, Portier CJ, Kuhn M, Thormann W, Scholtysik G, Mevissen M.Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electr...
Love S.Since 1917, only 11 new endoparasiticides have been developed for the horse, of which five chemical classes are in common use. The selection pressure of frequent administration of deworming doses for parasite control programs has been associated with the development of resistance of small strongyle parasites to the effects of benzimidazoles and pyrantel salts. Against the background of the inevitability of the occurrence of ivermectin/moxidectin resistance, responsible use of equine anthelmintics based on the clinical pharmacology of the compounds and the biology/epidemiology of intestinal par...
Monreal L, Sabaté D, Segura D, Mayós I, Homedes J.The objective was to compare the gastrointestinal and general toxicity of suxibuzone (SBZ) to that of phenylbutazone (PBZ) when administered orally in horses. Fifteen healthy horses were allocated to three treatment groups. One group received a high dose of PBZ for two weeks; the second group was given an equimolecular dosage of SBZ; and a third group received placebo. Horses were daily monitored, and blood samples were collected before and during the study. On day 18, complete post-mortem examinations were performed. One horse treated with PBZ showed clinical signs of NSAID toxicosis. Small o...
Davis JL, Stewart T, Brazik E, Gilger BC.The purpose of this study was to determine the influence of age, breed and gender on vertical pupil diameter (VPD) following a single dose of 1% atropine sulfate ophthalmic solution in the normal equine eye. Methods: Thirty-two horses of various ages, breeds and genders were included. The horses had no history or clinical signs of ophthalmic disease. All horses studied had darkly pigmented irides. Methods: Two milligrams of 1% atropine sulfate ophthalmic solution was topically administered as a single dose in the right eye of each horse on Day 0. The VPD (mm) was measured in both eyes using di...
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...
Roussel AJ, Hooper RN, Cohen ND, Bye AD, Hicks RJ, Schulze JL.To evaluate effects of IV administration of penicillin G potassium (KPEN) or potassium chloride (KCl) on defecation and myoelectric activity of the cecum and pelvic flexure of horses. Methods: 5 healthy horses. Methods: Horses with 12 bipolar electrodes on the cecum and pelvic flexure received KPEN or KCl solution by IV bolus 4 hours apart. Each horse received the following: 2 X 10(7) U of KPEN (high-dose KPEN) followed by 34 mEq of KCl (high-dose KCl), 1 X 10(7) U of KPEN (low-dose KPEN) followed by 17 mEq of KCl (low-dose KCl), high-dose KCl followed by high-dose KPEN, and low-dose KCl follo...
Broome TA, Brown MP, Gronwall RR, Casey MF, Meritt KA.Six healthy adult horses (5 mares and 1 stallion) were given a single dose of acetylsalicylic acid (ASA), 20 mg/kg of body weight, by intravenous (IV), rectal, and intragastric (IG) routes. Serial blood samples were collected via jugular venipuncture over a 36-h period, and plasma ASA and salicylic acid (SA) concentrations were determined by high-performance liquid chromatography. After IV administration, the mean elimination rate constant of ASA (+/- the standard error of the mean) was 1.32 +/- 0.09 h(-1), the mean elimination half-life was 0.53 +/- 0.04 h, the area under the plasma concentra...
Moens Y, Lanz F, Doherr MG, Schatzmann U.To study the analgesic potency of the alpha2-agonist romifidine in the horse using both an electrical current and a mechanical pressure model for nociceptive threshold testing. In addition, a comparison was made with doses of detomidine and xylazine that produce equivalent degrees of sedation. Methods: Randomized, placebo-controlled, blinded cross-over study. Methods: Six adult Swiss warmblood horses, one mare and five geldings, weighing from 530 to 650 kg and aged 6-15 years. Methods: Nociceptive thresholds were measured using an electrical stimulus applied to the coronary band and using a pn...
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...
Massoco C, Palermo-Neto J.Benzodiazepines (BDZ) are among the most frequently used class of psychotropic drugs employed in veterinary medicine in Brazil and worldwide due to their anxiolytic, muscle relaxant and anticonvulsant effects [J. Clin. Pharmacol. 33 (1993) 124]. Peripheral benzodiazepine receptor (PBR) sites were described in peripheral organs, endocrine steroidogenic tissues and immune organs and cells. Midazolam is a mixed-type agonist of PBRs. The present study is focused on the effects of midazolam on equine peripheral blood neutrophils, peritoneal macrophages and cortisol levels in plasma. Adult horses we...
Abraham G, Kottke C, Dhein S, Ungemach FR.Although in the respiratory system there is great therapeutic interest in manipulating and understanding the beta-adrenoceptor-G-protein-adenylate cyclase (AC) signal transduction pathway, little is known on segmental differences among lung, bronchus, and trachea with regard to the receptor concentration and interaction to G-proteins and coupling to AC. In this study, patterns of distribution and absolute quantities of beta-adrenoceptor subtypes beta(1) and beta(2) were determined in membranes of equine lung parenchyma, bronchial and tracheal epithelium with the underlying smooth muscle by sat...
Abo El Sooud K.The pharmacokinetics of gentamicin was studied in lambs, calves and foals, respectively after single intravenous (i.v.) injections of 5 mg kg(-1) body weight. The plasma concentration-time curves of gentamicin sulphate were best fitted to follow a two-compartment open model in calves and foals and a three-compartment open model in lambs. Gentamicin showed high plasma level at 5 min post-injection. Then its concentration decreased gradually until its minimum detectable level at 10 and 12 h post-injection in foals and calves, respectively, was reached. In contrast, the plasma concentrations were...
Frias AF, Mársico F, Gómez de Segura IA, Nascimento PR, Nascimento A, Soares JH, Almosny NR.To characterize responses to different doses of propofol in horses pre-medicated with xylazine. Methods: Six adult horses (five females and one male). Methods: Each horse was anaesthetized four times with either ketamine or propofol in random order at 1-week intervals. Horses were pre-medicated with xylazine (1.1 mg kg-1 IV over a minute), and 5 minutes later anaesthesia was induced with either ketamine (2.2 mg kg-1 IV) or propofol (1, 2 and 4 mg kg-1 IV; low, medium and high doses, respectively). Data were collected continuously (electrocardiogram) or after xylazine administration and at 5, 1...
Martínez AC, Hernández M, Rivera L, Recio P, García-Sacristán A, Benedito S.To investigate the effect of acetylcholine (ACh) on horse deep dorsal penile vein and to characterize the muscarinic receptor subtypes involved in this response. Methods: Vein rings were mounted in an organ bath chamber, and the isometric tension was recorded. Results: In phenylephrine-contracted veins, ACh (1 nM to 1 microM) induced endothelium-dependent relaxation. The muscarinic receptor antagonist, atropine, produced parallel rightward shifts of the ACh response curves (pA2 = 10.04; pK(B) = 9.98). Carbachol (10 nM to 100 microM) also evoked relaxation in the vein segments, but showed a low...
Pérez R, Godoy C, Palma C, Cabezas I, Muñoz L, Rubilar L, Arboix M, Alvinerie M.A study was undertaken in order to evaluate and compare ivermectin's (IVM) plasma disposition kinetic parameters after oral or intramuscular (IM) administration in horses. Ten clinically healthy adult horses, weighing 380-496 kg body weight (BW), were allocated to two experimental groups of five horses. Group I, was treated with an oral paste formulation of IVM at the manufacturer's recommended dose of 0.2 mg/kg BW. Group II, was treated IM with an injectable 1% formulation of IVM at a dose of 0.2 mg/kg BW. Blood samples were collected by jugular puncture at different times between 0.5 h and 7...
López-Sanromán J, Cruz J, Santos M, Mazzini R, Tabanera A, Tendillo FJ.The objective of this study was to determine the effects of the alkalinization on the local analgesic efficacy of 1% ketamine in the abaxial sesamoid nerve block in horses. Thirty-six mature healthy horses were randomly assigned to four groups for the following treatments; an abaxial sesamoid block with 5 mL of saline solution (control saline); an abaxial sesamoid block with 5 mL of a solution containing 1% ketamine (KETs 1%); an abaxial sesamoid block with 5 mL of a solution containing saline solution and 0.5 mEq of sodium bicarbonate (control bicarbonate); and an abaxial sesamoid block with ...
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...
Chou CC, Vickroy TW.To determine the presence of adenosine receptor subtypes A1 and A2a in equine forebrain tissues and to characterize the interactions of caffeine and its metabolites with adenosine receptors in the CNS of horses. Methods: Brain tissue specimens obtained during necropsy from 5 adult male research horses. Methods: Membrane-enriched homogenates from cerebral cortex and striatum were evaluated by radioligand binding assays with the A1-selective ligand [3H]DPCPX and the A2a-selective ligand [3H]ZM241385. Functional responses to adenosine receptor agonists and antagonists were determined by a nucleot...
McManus CJ, Fitzgerald BP.A small percentage of mature mares continue to exhibit estrous cyclicity during the non-breeding season which is of interest because of the importance of timing of the breeding season to the equine breeding industry. Previously, it was demonstrated that the continuation of estrous cycles was more likely to occur in mature than young mares. Additionally, an apparent association exists between elevated body fat and increased circulating concentrations of leptin, and the occurrence of estrous cycles during the non-breeding season. Two experiments were conducted to test the hypothesis that pharmac...
Berry DB, Sullins KE.To determine whether povidone iodine ointment or 2 forms of silver sulfadiazine applied topically to wounds of the distal aspect of the limbs in horses affect the rate of second intention healing and to evaluate the additional influence of bandaging with these antimicrobials on granulation tissue formation. Methods: 6 healthy adult horses. Methods: Six standardized 2.5-cm2 skin wounds/horse were distributed between the dorsomedial surfaces of the metacarpi and metatarsi. One of the following 6 treatments was applied to each wound: 1% silver sulfadiazine cream with bandage, 1% silver sulfadiazi...
Lees P, Landoni MF.Carprofen is a nonsteroidal anti-inflammatory drug of the 2-arylpropionate subclass. It contains a single chiral centre and exists in two enantiomeric forms. In this study rac-carprofen, at two dosages, 0.7 and 4.0 mg/kg, and placebo were administered i.v. to six New Forest horses in a three period cross-over study. The concentration-time profiles were established for R(-) and S(+)-carprofen for plasma and both inflamed (exudate) and noninflamed (transudate) tissue cage fluids. R(-)-carprofen was the predominant enantiomer in all three fluids, as indicated by plasma area under the curve (AUC) ...
Cohen ND, Hu Z, Stanley SD, Wang N.Furosemide is frequently used to control or prevent exercise-induced pulmonary hemorrhage in performance horses. The bronchodilating agent clenbuterol is also commonly used as a treatment for inflammatory airway disease in performance horses. Use of both medications is regulated by many racing authorities. The effects of concomitant administration of furosemide and clenbuterol on the pharmacokinetics of clenbuterol have not been well characterized. A study was designed to evaluate the influence of furosemide on serum and urine concentrations of clenbuterol after oral administration of clenbute...
Van Hoogmoed LM, Snyder JR, Harmon FA.To evaluate the effect of 2 cyclooxygenase (COX)-2 inhibitors on contractile activity of the circular smooth muscle layer of the equine dorsal and ventral colon. Methods: Samples of the dorsal and ventral colon obtained from 10 healthy horses. Methods: Full-thickness tissue samples were collected from the dorsal colon in the area of the diaphragmatic flexure and the ventral colon in the area of the sternal flexure. Samples were cut into strips oriented along the fibers of the circular muscle layer and mounted in a tissue bath system for determination of contractile strength. Incremental amount...
Guillaume D, Bruneau B, Briant C.The effects of two GnRH antagonists were tested in order to delay and/or synchronise ovulation in mares. Five mares received Antarelix (0.01 mg.kg(-1)), 5 mares received Cetrorelix (the same dose), 5 mares (control mares) received the vehicle intravenously, twice daily, for 8 days from the day the largest follicle reached 22 mm following prostaglandin administration. Ovulation was postponed in all mares injected with Antarelix (19.4 +/- 1.2 days after the beginning of the treatment) and in 2/5 mares injected with Cetrorelix (20 +/- 1 days) vs. 6.2 +/- 0.4 days in control mares. During the trea...
Yamashita K, Muir WW, Tsubakishita S, Abrahamsen E, Lerch P, Hubbell JA, Bednarski RM, Skarda RT, Izumisawa Y, Kotani T.To compare the analgesic and cardiopulmonary effects of medetomidine and xylazine when used for premedication of horses undergoing general anesthesia. Methods: Randomized clinical trial. Methods: 40 horses. Methods: Twenty horses were premedicated with medetomidine (10 microg/kg [4.5 microg/lb], i.m.) and the other 20 were premedicated with xylazine (2 mg/kg [0.9 mg/kg], i.m.). Horses were then anesthetized with a combination of guaifenesin and ketamine; anesthesia was maintained with halothane. Additional doses of medetomidine or xylazine were given if horses were not sufficiently sedated at ...
Cavalli M, Carcano R, Beretta C.Despite assays on ring preparations in vitro confirmed that the vasoconstrictor sympathetic control in the horse common digital artery mainly depends on alpha(1)-adrenoceptors stimulation, selective alpha(2)-adrenoceptor agonists were investigated under the same experimental conditions. Both detomidine (DET) and UK 14304 differed from noradrenaline (NA) and phenylephrine (PHE) in provoking contractile effects which were slowly onsetting, concentrations-unrelated and unremovable by repeated washings. While prazosin (PRA) clearly antagonized the effects of NA and PHE, neither pre- nor post-treat...
Daunt DA, Dunlop CI, Chapman PL, Shafer SL, Ruskoaho H, Vakkuri O, Hodgson DS, Tyler LM, Maze M.Cardiopulmonary and behavioral responses to detomidine, a potent alpha 2-adrenergic agonist, were determined at 4 plasma concentrations in standing horses. After instrumentation and baseline measurements in 7 horses (mean +/- SD for age and body weight, 6 +/- 2 years, and 531 +/- 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 +/- 0.5 (infusion 1), 7.2 +/- 3.5 (infusion 2), 19.1 +/- 5.1. (infusion 3), and 42.9 +/- 10 (infusion 4) ng/ml, by use of a computer-controlled infusion system. Detomidine caused concentration-dependent sedation and somnolence. The...
Prades M, Brown MP, Gronwall R, Houston AE.After single oral administration of ketoconazole (30 mg/kg bodyweight [bwt]) in 50 ml of corn syrup to a healthy mare, the drug was not detected in serum. Ketoconazole in 0.2 N HC1 was administered intragastrically to six healthy adult horses in five consecutive doses of 30 mg/kg bwt at 12 h intervals. Ketoconazole concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid (CSF), urine and endometrium. Mean peak serum ketoconazole concentration was 3.76 micrograms/ml at 1.5 to 2 h after intragastric administration. Mean peak synovial concentration was 0.87 mic...
Knych HK, Corado CR, McKemie DS, Scholtz E, Sams R.Tramadol is a synthetic opioid used in human medicine, and to a lesser extent in veterinary medicine, for the treatment of both acute and chronic pain. In humans, the analgesic effects are owing to the actions of both the parent compound and an active metabolite (M1). The goal of the current study was to extend current knowledge of the pharmacokinetics of tramadol and M1 following oral administration of three doses of tramadol to horses. A total of nine healthy adult horses received a single oral administration of 3, 6, and 9 mg/kg of tramadol via nasogastric tube. Blood samples were collected...
Flaherty D, Reid J, Welsh E, Monteiro AM, Lerche P, Nolan A.The pharmacodynamics of infusions of propofol alone (group 1) were compared with the pharmacodynamics of infusions of propofol and ketamine together (group 2) in eight ponies undergoing castration. Anaesthesia was induced with detomidine, 20 micrograms kg-1, followed by ketamine, 2.2 mg kg-1. Subsequently, a bolus dose of propofol, 0.5 mg kg-1, was administered intravenously to both groups, and an infusion of propofol was given for an average of 74 minutes to group 1, and an infusion of propofol and ketamine was given for 60 minutes to group 2. The mean (SD) infusion rates of propofol were 0.3...
Gronert GA, Fung DL, Jones JH, Shafer SL, Hildebrand SV, Disbrow EA.We investigated the effects of body size on the pharmacokinetics and pharmacodynamics of the renally cleared muscle relaxant metocurine. We hypothesized that pharmacokinetics of the drug would change allometrically in proportion to physiological time [infinity Mb0.25, where Mb is body mass] and that pharmacodynamics would be independent of size because of the highly conserved structure of the acetylcholine receptor. Metocurine effects during general anesthesia were examined in 17 rats, 8 cats, 6 dogs, 5 pigs, 7 sheep, and 12 horses. Allometric analysis demonstrated size dependence for pharmaco...
Poth MKM, McKemie DS, Traynham M, Kass PH, Knych HK.The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6-glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a...
Barton MH, Ferguson D, Davis PJ, Moore JN.Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F1 alpha were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at ...
Louie EW, Berryhill EH, Nieto J, Wensley F, Knych H, Finno CJ, Morgan JM.Gastric ulceration can be induced by athletic training and is a significant welfare concern. The objective of this study was to evaluate the effect of gastric ulcer induction on heart rate variability (HRV) in the horse. We hypothesized that induction of gastric ulcers would decrease HRV and increase low frequency fluctuations, consistent with increased sympathetic tone. A convenience sample of 8 horses in a larger study were enrolled. Horses were randomly assigned to receive water or 2 mg/kg omeprazole orally once daily for 28 days. Gastric ulcers were induced through intermittent feed withho...
Skrzypczak H, Reed R, Brainard B, Sakai D, Barletta M, Quandt J, Smyth C, Ruch M, Knych H.Matrix fentanyl patches have not been investigated in horses and may represent an effective means of providing analgesia over an extended time period without venous catheterisation. Objective: To describe the pharmacokinetics of a matrix transdermal fentanyl patch in horses. Methods: Randomised experiment, Latin-square design. Methods: Six adult horses were given each of three treatments with a 96-hour washout. For each treatment, two 100 µg/h matrix fentanyl patches were applied to the inguinal region (TXA), metacarpus (TXM) or ventral tail base (TXT) for 72 hours. Blood samples for fentan...
Lopez BS, Giguère S, Berghaus LJ, Mullins MA, Davis JL.The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N-desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N-desmethyldanofloxacin were measured by UPLC-MS/MS. After i.v. administration, da...
Tobin T, Blake JW, Valentine R.The plasma half-life of phenylbutazone in horses was not increased after pretreatment with chloramphenicol or quinidine, but was increased after oxyphenbutazone. This increased plasma half-life after oxyphenbutazone is consistent with observations in other species and suggests that oxyphenbutazone inhibits the metabolism of phenylbutazone in horses. Lack of inhibition of phenylbutazone metabolism in the horse by chloramphenicol and quinidine is inconsistent with results obtained in other species.
Elliott J, Soydan J.Isolated equine digital veins (EDVs) were used to study beta-adrenoceptor mediated vasodilation and to examine isoxsuprine's vasodilatory mechanism of action. When the blood vessel wall tension was raised with potassium chloride solution (KCl; 59 mmol/l), the order of vasodilator potency of beta-agonists was: isoprenaline > fenoterol > noradrenaline > dobutamine > isoxsuprine. The beta 2-selective adrenoceptor antagonist, ICI 118551 (1 nmol/l) caused a 6.74 and 6.65-fold parallel shift to the right in the dose response curves to fenoterol and noradrenaline respectively. Propranolol...
Tofflemire KL, Whitley EM, Flinn AM, Dufour VL, Ben-Shlomo G, Allbaugh RA, Griggs AN, Peterson CS, Whitley DR.To compare the effect of commercially available solution and compounded ointment formulations of dorzolamide(2%)-timolol(0.5%) on intraocular pressure (IOP) of normal horses. Methods: Eighteen clinically normal horses. Methods: A randomized, masked prospective design was used with horses divided into two equal groups. One eye of each horse was selected for topical ophthalmic treatment with either 0.2 mL of dorzolamide(2%)-timolol(0.5%) solution or 0.2 g of dorzolamide(2%)-timolol(0.5%) ointment every 12 h for 5 days. The contralateral eye of horses in both groups was untreated. Rebound tonomet...
Tavanaeimanesh H, Azarnoosh A, Ashar FS, Dehghan MM, Mohebbi Z, Akbarinejad V, Corley K.The choice of analgesic agents for the horse is limited, and many have side effects that can restrict their use for chronic and prolonged pain. Little information has been published on tramadol and acetaminophen use in the horse. The study evaluated the analgesic effects of coadministration of tramadol and acetaminophen compared to those of each drug individually in a crossover study. The study was performed on six healthy horses each infused with the following over 1 hour: control (normal saline), tramadol, acetaminophen, or both (acetaminophen and tramadol infused together). Nociception (usi...
Hamamoto-Hardman BD, Steffey EP, McKemie DS, Kass PH, Knych HK.Meperidine is a synthetic opioid that belongs to the phenylpiperidine class and is a weak mu receptor agonist. In horses there are a limited number of published studies describing the analgesic effects of systemically administered meperidine in horses. The objective of this study was to describe the pharmacokinetics, behavioral and physiologic effects and effect on thermal threshold of three doses of intravenously administered meperidine to horses. Eight University owned horses (four mares and four geldings, aged 3-8 years were studied using a randomized balanced 4-way cross-over design. Hors...
Gretler SR, Finno CJ, McKemie DS, Kass PH, Knych HK.To describe the pharmacokinetics and selected pharmacodynamic variables of codeine and its metabolites in Thoroughbred horses following a single oral administration. Methods: Prospective experimental study. Methods: A total of 12 Thoroughbred horses, nine geldings and three mares, aged 4-8 years. Methods: Horses were administered codeine (0.6 mg kg) orally and blood was collected before administration and at various times until 120 hours post administration. Plasma and urine samples were collected and analyzed for codeine and its metabolites by liquid chromatography-mass spectrometry, and plas...
Guillaume D, Bruneau B, Briant C.The effects of two GnRH antagonists were tested in order to delay and/or synchronise ovulation in mares. Five mares received Antarelix (0.01 mg.kg(-1)), 5 mares received Cetrorelix (the same dose), 5 mares (control mares) received the vehicle intravenously, twice daily, for 8 days from the day the largest follicle reached 22 mm following prostaglandin administration. Ovulation was postponed in all mares injected with Antarelix (19.4 +/- 1.2 days after the beginning of the treatment) and in 2/5 mares injected with Cetrorelix (20 +/- 1 days) vs. 6.2 +/- 0.4 days in control mares. During the trea...
Gardner SY, Atkins CE, Sams RA, Schwabenton AB, Papich MG.The pharmacokinetics of enalapril (0.5 mg/kg i.v.) and the pharmacodynamics of enalapril (0.5 mg/kg PO) in 5 mares were investigated. After single i.v. dosing, concentrations of enalapril and enalaprilat, its active metabolite, were measured. Two weeks later, enalapril was administered by nasogastric tube. Potassium, creatinine, blood urea nitrogen (BUN), enalapril, and enalaprilat concentrations and angiotensin converting enzyme (ACE) activity were measured in serum. In addition, heart rate, blood pressure, digital venous blood gases, and lactate were measured. Two weeks later, enalapril was ...
Hoffmann SL, Seminoff K, McKemie DS, Kass PH, Knych HK.Grapiprant is a prostaglandin E2 receptor antagonist that has been found to be an effective anti-inflammatory in dogs and that is devoid of some of the adverse effects associated with traditional NSAIDs that elicit their effects through inhibition of PGE2 production. Previously published reports have described the pharmacokinetics of this drug in horses when administered at 2 mg/kg; however, pharmacodynamic effects in this species have yet to be described. The objective of the current study was to describe the pharmacokinetics and pharmacodynamics of grapiprant at a higher dose. Eight horses...
Wilson KE, Bogers SH, Council-Troche RM, Davis JL.To determine the effects of general anesthesia on the safety and efficacy of co-administered potassium penicillin G (PEN) and gentamicin (GENT) in horses. Methods: Nonrandomized crossover. Methods: Six adult, Thoroughbred horses. Methods: Horses were administered PEN (22 000 IU/kg IV) and GENT (6.6 mg/kg IV). Plasma samples were collected over a 6 h period and synovial fluid was collected at 30 min and 6 h respectively. Drug administration and sample collection protocols were repeated after at least a 48 hour washout period and induction of anesthesia using xylazine/ketamine and main...
Iff I, Mosing M, Moens Y.The objectives of this study were to measure the pressure in the caudal extradural space of standing horses and to evaluate the usefulness of pressure waves to identify correct needle placement. Caudal extradural pressure was measured in 12 healthy horses. The pressure and any extradural pressure waves were recorded for 3min after puncture, for 1min after testing for lack of resistance (LOR), and for 10min after lidocaine injection. Successful extradural drug administration was confirmed in all horses. The median extradural pressure findings after puncture, after LOR, immediately after injecti...
Olsén L, Ingvast-Larsson C, Bondesson U, Broström H, Tjälve H, Larsson P.The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9-3.7 h) and the maximal plasma concentration 132 ng/mL (101-196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5-0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h be...
Zerpa H, Berhane Y, Elliott J, Bailey SR.Cooling-enhanced contractile responses in cutaneous arteries have been reported to involve the activation of alpha(2C)-adrenoceptors, but their role in cutaneous veins is not clearly understood. The aim was to pharmacologically characterize the subtype of postsynaptic alpha(2)-adrenoceptors in the equine digital vein mediating contraction at two temperatures. The increase in isometric tension of endothelium-denuded equine digital vein in response to UK-14304 was studied in the absence and presence of relatively selective alpha(2)-adrenoceptor antagonists at temperatures of either 30 degrees C ...
Baker SJ, Gerring EL.We investigated the effects of a range of IV administered doses of omeprazole (0.125 to 2.0 mg/kg of body weight) on gastric pH (monitored by indwelling electrode) and plasma gastrin concentration, compared with those of IV administered ranitidine (1.0 mg/kg) in 4 Welsh mountain-type ponies. Pharmacokinetic variables of IV administered omeprazole also were examined. Episodes of high gastric pH in the basal state obscured the effect of acid suppression on intragastric pH; however, omeprazole induced dose-dependent increase in mean gastric pH (P < 0.01) during the 11 hours after its administr...
Mills PC, Ng JC, Seawright AA, Auer DE.Vascular leakage induced by intradermal injection of endotoxin, zymosan-activated plasma (ZAP) and platelet-activating factor (PAF) was measured in nine Thoroughbreds using 125-iodine human serum albumin (125I-HSA) as a marker in the blood. ZAP and PAF produced dose-dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose-dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of e...
Guthrie AJ, Beadle RE, Bateman RD, White CE.This paper presents a method for on-line determination of pulmonary mechanics in standing, non-sedated horses during and following inhalation of aerosolized drug solutions. This method was used to evaluate the temporal effects of inhaled histamine and methacholine aerosols on pulmonary mechanics in 18 Thoroughbred horses. The following were concluded from this study. The extremely large between-breath variation, for all variables used to evaluate pulmonary mechanics in the horse, limits the usefulness of these variables for modeling the non-specific pulmonary responses to inhaled stimulants on...
Guan F, Uboh CE, Soma LR, Birks EK, Teleis D, Rudy JA, Watson AO, Tsang DS.A reliable and sensitive method for the extraction and quantification of phenytoin (5,5'-diphenylhydantoin), its major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) and minor metabolite, 5-(m-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) in horse urine and plasma is described. The method involves the use of solid-phase extraction (SPE), liquid-liquid extraction (LLE), enzyme hydrolysis (EH) and high-performance liquid chromatography (HPLC). The minor metabolite, 5-(m-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) was not present in a reliably quantifiable concentration in all samples. The ...
Rodríguez-Pozo ML, Armengou L, Monreal L, Viu J, Cesarini C, Jose-Cunilleras E.To assess whether an oral direct factor Xa inhibitor (DiXaI) anticoagulant drug used at the low end of the recommended dose in people achieves presumed prophylactic plasma concentrations and does not induce bleeding in horses. Methods: Experimental study. Methods: Field study. Methods: Ten healthy adult horses. Methods: A DiXaI was administered at a dose of 0.125 mg/kg every 24 h orally for 4 days. Following a wash-out period of 2 weeks, 8 of 10 horses received daily subcutaneous doses of a low molecular weight heparin (dalteparin) for 4 consecutive days at 50 IU/kg. In both trials, antifactor...
Peroni JF, Moore JN, Noschka E, Lewis TH, Lewis SJ, Robertson TP.To characterize the relative contributions of voltage-gated and capacitative Ca(2+) entry to agonist-induced contractions of equine laminar arteries and veins. Methods: 16 adult mixed-breed horses. Methods: Laminar arteries and veins were isolated and mounted on small vessel myographs for the measurement of isometric tension. Concentration-response curves were obtained for the vasoconstrictor agonists phenylephrine, 5-hydroxytryptamine (5-HT), prostaglandin F(2) (PGF(2)), and endothelin-1 (ET-1) either in the absence of extracellular Ca(2+) or in the presence of the voltage-gated Ca(2+) channe...
Venugopal CS, Holmes EP, Koch CE, Curtis LA, Holm AS, Moore RM.To evaluate the effectiveness of 2 potential endothelin (ET)-1 antagonists in blocking the contractile responses of equine colonic vessels to increasing concentrations of ET-1. Methods: Mesenteric vessels from 6 clinically healthy horses. Methods: Colonic vessels (arterial and venous rings) were placed in organ baths with oxygenated Tyrode solution at 37 C. Each was attached to a force transducer interfaced with a polygraph, and 2 g of tension was applied and equilibrated for 45 minutes. Then, B-1 (PD 142893) and B-2 (PD 145065) ET-1 antagonists were tested. One ring from each vessel type was ...
