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.
Maher MC, Schnabel LV, Cross JA, Papich MG, Divers TJ, Fortier LA.To determine whether low-dose, low-frequency doxycycline administration is capable of achieving chondroprotective concentrations within synovial fluid (SF) while remaining below minimum inhibitory concentration 90 (MIC90 ) of most equine pathogens and would be an option in the management of osteoarthritis. Objective: To determine whether low-dose, low-frequency oral administration of doxycycline can attain in vivo SF concentrations capable of chondroprotective effects through reduction of matrix metalloproteinase (MMP)-13 activity, while remaining below MIC90 of most equine pathogens. Method...
Foreman JH, Ruemmler R.There are no peer reviewed, blinded controlled studies regarding the skeletal analgesic efficacy of intramuscularly administered meperidine in horses. Objective: Using an adjustable heart bar shoe model of equine foot pain, the objective of this study was to test the hypothesis that meperidine (pethidine) administered intramuscularly would prove more efficacious in alleviating lameness than a saline placebo. Methods: Crossover pharmacodynamic experiment. Methods: Eight healthy adult Thoroughbred horses randomly underwent weekly i.m. treatments 1 h after lameness induction: saline placebo (1â...
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...
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...
Ringer SK, Schwarzwald CC, Portier K, Mauch J, Ritter A, Bettschart-Wolfensberger R.The aim of the present study was to investigate changes in blood glucose concentration ([Glu]B), acid-base status and electrolyte concentrations during constant rate infusions (CRI) of two alpha2-adrenergic agonists in seven horses treated in a blinded, randomised, crossover design with xylazine or romifidine. An intravenous (IV) bolus of xylazine (1mg/kg) or romifidine (80 μg/kg) was administered followed by an IV CRI of xylazine (0.69 mg/kg/h) or romifidine (30 μg/kg/h) for 2h. Blood samples were collected from the pulmonary artery before and after loading doses, during the CRI, and for 1h...
Hyde RM, Lynch TM, Clark CK, Slone DE, Hughes FE.This study investigated the influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion (IVRLP) and assessed the efficacy of low volume IVRLP. The front limbs of 9 horses were randomly assigned to 1 of 3 volume groups: 10 mL (Group 1), 30 mL (Group 2), or 60 mL (Group 3). A tourniquet was applied distal to the carpus and the limbs were perfused with 500 mg genta-micin diluted to the assigned volume via a catheter placed in the lateral palmar digital vein at the level of the proximal sesamoid bones. Synovial fluid samples were col...
We evaluated the vasorelaxant effect of propentofylline (PPF), a methylxanthine derivative, and its mechanism of action in equine digital veins (EDVs). Cumulative concentration-response curves to PPF (1 nM-300 µM) were recorded in phenylephrine-precontracted EDV rings under different experimental conditions. PPF-induced relaxation was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (an adenosine receptor antagonist; 3 µM). PPF-induced relaxation was partially inhibited in the presence of L-NAME (a nitric oxide (NO) synthase inhibitor; 100 µM), ODQ (an inhibitor of...
Cox S, Villarino N, Sommardahl C, Kvaternick V, Zarabadipour C, Siger L, Yarbrough J, Amicucci A, Reed K, Breeding D, Doherty T.The objective of this study was to determine if a single loading dose (LD), 3× the label dose of firocoxib oral paste, followed by nine maintenance doses at the current label dose achieves and maintains near steady state concentrations. Six healthy, adult mares were administered 0.3mg/kg of firocoxib on Day 0, and 0.1 mg/kg 24 h later on Day 1, and at 24 h intervals from Day 2 to Day 9, for a total of 10 doses. Blood samples were collected throughout the study. The mean firocoxib maximum plasma concentration and standard deviation was 199±97 ng/mL, 175±44 ng/mL and 183±50 ng/mL after the L...
Ambrisko TD, Moens Y.In a previous in vitro study using saline medium, the authors showed that certain drugs changed the voltages of lithium dilution cardiac output (LiDCO) sensors and also influenced their accuracy in measuring lithium concentrations. These two parameters correlated and so we examined whether such drug-sensor interaction exists when LiDCO sensor was exposed to xylazine in blood. Methods: Five healthy adult warm-blood horses were injected with 0.5 mg kg(-1) xylazine i.v. Physiological saline solution and venous blood were consecutively sampled through the same LiDCO sensor at 60, 45, 30, 15, and 0...
Mahne AT, Rioja E, Marais HJ, Villarino NF, Rubio-Martinez LM.Antimicrobial i.v. regional limb perfusion (IV-RLP) is clinically performed on anaesthetised or sedated horses with or without regional anaesthesia. To date, no scientific data are available on the clinical and pharmacokinetic effects of these anaesthetic protocols on antimicrobial IV-RLP, which is believed to result in better tourniquet efficiency due to decreased movement. Objective: To determine the effects of regional or general anaesthesia on the clinical and synovial pharmacokinetic parameters of amikacin administered by IV-RLP to horses. Methods: Experimental crossover study. Methods: E...
Afonso T, Giguère S, Rapoport G, Berghaus LJ, Barton MH, Coleman AE.Angiotensin-converting enzyme (ACE) inhibitors are used in horses with cardiovascular disorders despite the paucity of available data regarding their efficacy. Objective: The degree of serum ACE inhibition varies considerably between drugs. Methods: Eight healthy adult horses. Methods: Randomized prospective study. Horses were fasted overnight prior to receiving one of 4 ACE inhibitors intragastrically, administered at one of 2 dosages, using a randomized Latin square design (benazepril: 0.5 and 0.25 mg/kg; ramipril: 0.3 and 0.1 mg/kg; quinapril: 0.25 and 0.125 mg/kg; perindopril: 0.1 and 0.05...
Bäumer W, Herrling GM, Feige K.To test the efficacy of the recombinant tissue-type plasminogen activator (rt-PA) alteplase in horses, the thrombolytic effect was tested in in vitro generated equine thrombi. The extent of lysis was determined by measuring the decrease in thrombi weight over a period of 4 hours. In vivo pharmacokinetics of alteplase were determined in 6 healthy horses. A single dose (1 mg/kg) was applied via intravenous infusion over a period of 30 minutes Coagulation-related variables, blood count and clinical parameters were taken before the treatment and until 48 h after treatment. In addition, plasma rt-P...
Rumpler MJ, Kandala B, Vickroy TW, Hochhaus G, Sams RA.Glycopyrrolate (GLY) is an antimuscarinic agent that is used in humans and domestic animals primarily to reduce respiratory tract secretions during anesthesia and to reverse intra-operative bradycardia. Although GLY is used routinely in veterinary patients, there is limited information regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties in domestic animals, and an improved understanding of the plasma concentration-effect relationship in racehorses is warranted. To accomplish this, we characterize the pharmacokinetic-pharmacodynamic (PK-PD) actions of GLY during and after a 2...
Lallemand E, Trencart P, Tahier C, Dron F, Paulin A, Tessier C.To evaluate pharmacokinetic-pharmacodynamic variables and local tolerance at injection-site of marbofloxacin administered via regional intravenous limb perfusion (RIVLP) in standing horses. Methods: Adult horses (n = 6). Methods: RIVLP were performed with rubber tourniquets applied to the forelimbs of standing sedated horses. Marbofloxacin (0.67 mg/kg) was randomly injected in 1 forelimb, with the contralateral limb serving as a control (0.9% NaCl solution). Samples of jugular blood and synovial fluid from the radiocarpal joint of the marbofloxacin-perfused limb were collected before and...
Knych HK, Harrison LM, Casbeer HC, McKemie DS.Methylprednisolone acetate (MPA) is commonly administered to performance horses, and therefore, establishing appropriate withdrawal times prior to performance is critical. The objectives of this study were to describe the plasma pharmacokinetics of MPA and time-related urine and synovial fluid concentrations following intra-articular administration to sixteen racing fit adult Thoroughbred horses. Horses received a single intra-articular administration of MPA (100Â mg). Blood, urine, and synovial fluid samples were collected prior to and at various times up to 77Â days postdrug administration a...
Berghaus LJ, Giguère S, Guldbech K.The objectives of this study were to determine the mutant prevention concentration (MPC), time above the MPC and mutant selection window for 10 antimicrobial agents against Rhodococcus equi and to determine if the combination of a macrolide with rifampin would decrease emergence of resistant mutants. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, and doxycycline) were selected based on in vitro activity and frequency of use in foals or people infected with R. equi. Each antimicrobial agent or co...
Spallek A, Recknagel S, Breuer J, Koeller G, Schusser GF.The use of laxatives is crucial in the treatment of horses with large colon impaction. To reach the impacted mass, the laxative must leave the stomach and pass through the small intestine. The aim of this study was to determine whether the most frequently used saline and lubricant laxatives influence gastric emptying. Six fasted normal adult Warmblood horses were used in a randomized study design with five laxative trials (1.8% sodium sulfate [1.8% Na2SO4], 4.2% magnesium sulfate [4.2% MgSO4], mineral oil [MOil], 25% sodium sulfate [25% Na2SO4], 25% magnesium sulfate [25% MgSO4]) and two trial...
López-Sanromán FJ, Holmbak-Petersen R, Varela M, del Alamo AM, Santiago I.To evaluate the duration of effects on movement patterns of horses after sedation with equipotent doses of xylazine hydrochloride, detomidine hydrochloride, or romifidine hydrochloride and determine whether accelerometry can be used to quantify differences among drug treatments. Methods: 6 healthy horses. Methods: Each horse was injected IV with saline (0.9% NaCl) solution (10 mL), xylazine diluted in saline solution (0.5 mg/kg), detomidine diluted in saline solution (0.01 mg/kg), or romifidine diluted in saline solution (0.04 mg/kg) in random order. A triaxial accelerometric device was used f...
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...
Sørensen MA, Jacobsen S, Petersen LJ.Microdialysis is a method for sampling compounds from extracellular fluid with minimal tissue trauma. Small hollow probes that are 0.2-0.5mm in diameter are inserted into the tissue and slowly perfused. The probe membrane is semi-permeable and a flux of the solutes occurs exclusively according to the concentration gradients. The recovered dialysate reflects changes in the composition of the extracellular water phase with a minor time delay. Because microdialysis is a continuous sampling method, it differs from point sample methods, such as blood sampling. The ability to obtain local measuremen...
McMullen RJ, Davidson MG, Gilger BC.To determine the effects of tropicamide 1% on the refractive state of the adult equine globe and identify the most appropriate time period (in relation to mydriasis) to perform streak retinoscopy. Methods: Eight university-owned mares of various ages and breeds. Methods: Topical tropicamide 1% was applied to one randomly selected eye from each of the horses to induce mydriasis and cycloplegia. The contralateral eyes served as controls. Streak retinoscopy and pupillometry were performed prior to, and every 5 min after tropicamide 1% installation for 90 min. Results: All values are expressed as ...
Whelchel DD, Tennent-Brown BS, Giguère S, Epstein KL.To compare the pharmacodynamics of once daily and twice daily administration of low molecular weight heparin (LMWH) administration in horses. Methods: Randomized cross over study. Methods: Adult mixed breed healthy mares (n = 6). Methods: LMWH (dalteparin) was administered (50 U/kg subcutaneously) either every 12 or 24 hours for 3 consecutive days. Anti-factor Xa activity was measured before and at select time points after LMWH administration. Packed cell volume (PCV), platelet count, partial thromboplastin time (PTT), and anti-thrombin (AT) activity were monitored throughout the study. Result...
Nieto JE, Maher O, Stanley SD, Knych HK, Snyder JR.To determine the pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses. Methods: 8 healthy horses. Methods: A single dose of zoledronic acid (0.057 mg/kg, IV) was administered during a 30-minute period. Venous blood was collected at several time points. Zoledronic acid concentration in plasma was measured by liquid chromatography-tandem mass spectrometry, and pertinent pharmacokinetic parameters were determined. Plasma was analyzed for total calcium, BUN, and creatinine concentrations and a marker for bone resorption (C-terminal telopeptides of type I collagen). Results: ...
Newman JC, Prange T, Jennings S, Barlow BM, Davis JL.The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra-articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3-way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half-life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be...
Friebe M, Schumacher S, Stahl J, Kietzmann M.This study investigated synovial concentrations of acetylsalicylic acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint following systemic administration of ASA. Salicylates were chosen because SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist for plasma and urine in equine sports. To avoid animal experiments, the study was conducted using an ex vivo model of the isolated perfused equine distal limb in combination with plasma concentrations obtained from literature.Salicylate concentrations in the joint were determined using microdialy...
Kuroda T, Nagata S, Takizawa Y, Tamura N, Kusano K, Mizobe F, Hariu K.The pharmacokinetics of d-chlorpheniramine (CPM), a histamine H1-receptor antagonist, and its ability to inhibit of histamine-induced cutaneous wheal formation, were studied in healthy Thoroughbred horses (n=5). Following an intravenous (IV) dose of 0.5mg/kg bodyweight (BW), plasma drug disposition was very rapid, with the mean terminal half-life and total body clearance calculated as 2.7h and 0.7 L/h/kg, respectively. The observed maximal inhibition of wheal formation following IV doses of 0.1 and 0.5mg/kg BW were 37.8% and 60.6% at 0.5h, respectively. Oral administration of CPM (0.5mg/kg BW)...
Zozaya H, Gutierrez L, Bernad MJ, Sumano H.Doxycyline (Dox) is a semisynthetic antibacterial drug with pharmacological advantages over its parent drug (tetracycline) in the treatment of various bacterial diseases in horses. Yet, at present a horse-customized pharmaceutical formulation is not available. Based on its pharmacokinetic/pharmacodynamic (PK/PD) ratio, Dox is considered a time-dependent antibacterial drug and ideally expected to achieve sustained plasma drug concentrations both at or slightly above the minimal inhibitory concentration (MIC) level for as long as possible between dosing intervals. Hence, the objective of this st...
Pucket JD, Allbaugh RA, Rankin AJ, Ou Z, Bello NM.To compare efficacy and duration of effect on corneal sensitivity of 0.5% proparacaine hydrochloride, 0.5% bupivacaine hydrochloride, 2% lidocaine hydrochloride, and 2% mepivacaine hydrochloride solutions following ocular administration in clinically normal horses. Methods: 68 clinically normal horses. Methods: 60 horses were assigned to receive 1 anesthetic agent in 1 eye. For each of another 8 horses, 1 eye was treated with each of the anesthetic agents in random order with a 1-week washout period between treatments. Corneal sensitivity was assessed via corneal touch threshold (CTT) measurem...
Yokota S, Hikasa Y, Shimura I, Kusunose S.To investigate effects of various imidazoline and nonimidazoline α-adrenergic agents on aggregation and antiaggregation of bovine and equine platelets. Methods: Blood samples obtained from 8 healthy adult cattle and 16 healthy adult Thoroughbreds. Methods: Aggregation and antiaggregation effects of various imidazoline and nonimidazoline α-adrenergic agents on bovine and equine platelets were determined via a turbidimetric method. Collagen and ADP were used to initiate aggregation. Results: Adrenaline, noradrenaline, or α-adrenoceptor agents alone did not induce changes in aggregation of bov...
Knych HK, Seminoff K, McKemie DS.Traditional therapeutic options for the treatment of lameness associated with inflammation in performance horses include administration of cyclooxygenase enzyme inhibiting non-steroidal anti-inflammatory drugs (NSAID). As long-term use of these drugs can adversely impact the health of the horse, anti-inflammatories with a more favorable safety profile are warranted. Grapiprant is a newly approved non-cyclooxygenase inhibiting NSAID that has demonstrated efficacy and safety in other species and which may be a valuable alternative to traditional NSAIDs used in the horse. The objectives of the cu...
Gokbulut C, Cirak VY, Senlik B, Yildirim F, McKellar QA.This study aimed to determine the plasma disposition and faecal excretion of netobimin (NTB) and its respective metabolites as well as the efficacy against strongyles in horses following oral administration. Netobimin (10mg/kg) was administered orally to 8 horses. Blood and faecal samples were collected from 1 to 120h post-treatment and analysed by high performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of ABZSO enantiomers produced was also determined. Faecal strongyle egg counts (EPG) were performed by a modified McMaster's technique before and afte...
Malone ED, Brown DR, Trent AM, Turner TA.To characterize the response of equine jejunal smooth muscle to adrenergic and cholinergic mediators. Methods: Evaluation of myogenic responses, using an in vitro model. Methods: Intestinal tissues were obtained from horses without gastrointestinal tract disorders or systemic disease. Methods: Baseline myogenic tone and amplitude and frequency of contraction were determined for suspended jejunal muscle strips. The level of adrenergic and cholinergic regulation was assessed, using atropine and adrenoceptor antagonists. The response of the muscles to norepinephrine was characterized, using adren...
Jaussaud P, Guieu D, Bellon C, Barbier B, Lhopital MC, Sechet R, Courtot D, Toutain PL.The pharmacokinetics of tolfenamic acid were studied in five ponies after an intravenous (iv) administration (2 mg/kg bodyweight [bwt]) and in four horses after an oral administration (30 mg/kg bwt) of tolfenamic acid. The plasma levels were determined by high pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). For the iv administration, a three-compartment model was used to represent the plasma concentration-time curve of the drug. The elimination half-life of the compound was 6.1 +/- 1.5 h, the total body clearance was 72.4 +/- 16.7 ml/kg bwt/h and the ste...
Pellegrini-Masini A, Poppenga RH, Sweeney RW.An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.
Foster AP, Lees P, Andrews MJ, Cunningham FM.Platelet-activating factor (PAF) causes oedema and neutrophil accumulation when injected into the skin of normal horses. PAF is also known to induce aggregation of horse platelets in vitro. The selective PAF receptor antagonist WEB 2086 has now been used to determine whether these effects are mediated by PAF receptor activation. Addition of WEB 2086 to equine platelets in vitro inhibited PAF-induced aggregation in a competitive reversible manner (pA2 = 7.14). Inhibition of in vivo inflammatory responses to PAF occurred after local administration of WEB 2086: wheal formation induced by 0.1 micr...
Fielding CL, Brumbaugh GW, Matthews NS, Peck KE, Roussel AJ.To determine the pharmacokinetics and clinical effects of a subanesthetic, continuous rate infusion of ketamine administered to healthy awake horses. Methods: 8 adult horses. Methods: Ketamine hydrochloride was administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6 mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse effects. Ketamine was then administered to 6 horses for a total of 12 hours (3 horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3 horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours). Conce...
von Fellenberg RL, Jordan JC, Ludwig B, Rehm WF.Aditoprim, a broad spectrum antimicrobial agent acting as a reversible dihydrofolate reductase inhibitor, was intravenously injected into four 12 to 24-year old horses at a dosage of 5 mg/kg b. w. Blood samples were collected over a 48-hour period after drug injection, and the separated plasma samples were assayed for aditoprim by high performance liquid chromatography. The body temperature, heart rate, respiration rate, and behaviour were recorded during the experiment. The bilirubin and urea concentrations were also determined in several plasma samples, and liver function tests were carried ...
Flynn H, Cenani A, Brosnan RJ, DiMaio Knych HK, de Araujo Aguiar AJ.To determine the pharmacokinetics and pharmacodynamics of high-concentration formulation of buprenorphine (1.8 mg mL; Simbadol) following subcutaneous (SC) administration in horses. Methods: Prospective, randomized, crossover trial. Methods: A group of six healthy adult horses weighing 521-602 kg. Methods: On three occasions, Simbadol (0.005 mg kg; treatment S5), (0.0025 mg kg; treatment S2.5) or saline (treatment SAL) were administered SC at least 7 days apart in random order. Electrical nociceptive threshold (ENT) measured on the neck region, physiologic variables, locomotor activity, degree...
McMullen RJ, Davidson MG, Gilger BC.To determine the effects of tropicamide 1% on the refractive state of the adult equine globe and identify the most appropriate time period (in relation to mydriasis) to perform streak retinoscopy. Methods: Eight university-owned mares of various ages and breeds. Methods: Topical tropicamide 1% was applied to one randomly selected eye from each of the horses to induce mydriasis and cycloplegia. The contralateral eyes served as controls. Streak retinoscopy and pupillometry were performed prior to, and every 5 min after tropicamide 1% installation for 90 min. Results: All values are expressed as ...
Segura D, Monreal L, Espada Y, Pastor J, Mayós I, Homedes J.The objective of this study was to assess whether a new human platelet function analyser (the PFA-100) could be used to evaluate platelet function in horses and detect acetylsalicylic acid (ASA)-induced platelet dysfunctions. Citrated blood samples from 40 healthy horses were processed to obtain reference values for closure time (CT) using cartridges with collagen-ADP (CT-ADP) and collagen-epinephrine (CT-EPI) as platelet agonists. In addition, CT-ADP and CT-EPI were also measured before and 24 h after oral ASA administration in another 12 healthy horses. The sensitivity and specificity of the...
Goodwin WA, Pasloske K, Keates HL, Ranasinghe MG, Woldeyohannes S, Perkins N.To determine the suitability of alfaxalone total intravenous (IV) anaesthesia in horses and concurrently evaluate infusion rates, cardiovascular effects, pharmacokinetics and the quality of the anaesthetic recovery period. Methods: Prospective, experimental study. Methods: Eight Standardbred horses. Methods: Horses were premedicated with IV acepromazine (0.03 mg kg) and xylazine (1 mg kg) and anaesthesia was induced with guaifenesin (35 mg kg) and alfaxalone (1 mg kg). Anaesthesia was maintained for 180 minutes using an IV infusion of alfaxalone at a rate determined by a horse's response to a ...
Ekstrand C, Bondesson U, Giving E, Hedeland M, Ingvast-Larsson C, Jacobsen S, Löfgren M, Moen L, Rhodin M, Saetra T, Ranheim B.Dexamethasone is used for the intra-articular route of administration in management of aseptic arthritis in horses. Despite its widespread use there is very little quantitative data of the disposition and response to dexamethasone. The aim of this study was to investigate and describe the synovial fluid and plasma dexamethasone concentration over time and to explore the relation between synovial fluid concentration and response using clinical endpoints as response biomarkers after IA injection of dexamethasone disodium salt solution in an equine model of synovitis. Results: Inflammation was in...
Young SS, Tesarowski D, Viel L.The effect of measurement frequency on respiratory mechanics was investigated in six horses with reversible allergic airway disease. Total respiratory impedance was measured at 1.5, 2.0, 3.0, and 5.0 Hz by using the forced oscillation technique with the horses in remission, after acute antigenic challenge producing clinical heaves, and with heaves but after the administration of 2 mg fenoterol by inhalation. The slopes of the magnitude (magnitude of Zrs) and real part (R) of total respiratory impedance over the frequency range 1.5-3 Hz changed significantly after antigenic challenge and fenote...
Moore JN, Mahaffey EA, Zboran M.Heparin was administered subcutaneously 2 times a day for 4 days to 5 horses. An additional group of 5 horses was used as time-matched controls. Significant decreases in PCV, erythrocyte count, and hemoglobin concentration were observed during heparin therapy. The mean corpuscular volume (MCV) of the heparin-treated horses increased to a peak value of 66.1 fl on the last day of treatment. Erythrocyte creatine concentration and glucose 6-phosphate dehydrogenase activity increased moderately during the treatment. These data indicated that the rapid, profound increase in MCV during heparin therap...
Whitehair KJ, Blevins WE, Fessler JF, Van Sickle DC, White MR, Bill RP.Regional perfusion of carpal tissues by forced intramedullary administration of fluids was evaluated in 10 horses. Results of subtraction radiography after perfusion with a contrast medium demonstrated that perfusate was delivered to the carpal tissues by the venous system. Perfused India ink was distributed uniformly in the antebrachiocarpal and middle carpal synovial membranes. Histologically, the ink was within the venules of the synovial villi. Immediately after perfusion with gentamicin sulfate (1 g), the gentamicin concentrations in the synovial fluid and synovial membrane of the antebra...
Murray MJ, Grodinsky C.Gastric fluid pH was measured in five adult horses following nasogastric administration of famotidine, 0.5, 1.0, and 2.0 mg/kg bodyweight (bwt); ranitidine, 4.4 and 6.6 mg/kg bwt and an antacid containing magnesium hydroxide (40 mg/ml) and aluminium hydroxide (45 mg/ml), 120 and 180 ml. Fluid was aspirated through a 16 French nasogastric feeding tube at 15 min intervals, and pH was measured using a pH meter. Basal gastric fluid pH was measured at 20 min intervals for 6 h in each horse and, with the exception of two measurements of 4.66 and 4.17, ranged from 1.42 to 2.41, with a mean pH of 1.88...
Sanchez LC, Robertson SA, Maxwell LK, Zientek K, Cole C.Transdermal fentanyl is used clinically in horses based on pharmacokinetic data and antinociceptive effects documented in other species. Objective: Fentanyl IV administration increases both visceral and somatic nociceptive threshold in conscious horses. Methods: Six clinically normal horses, each fitted with a permanent gastric cannula. Methods: Visceral nociception was evaluated with 2 methods of threshold detection--olorectal distention and duodenal distention. Somatic nociception was assessed by measurement of thermal threshold. Fentanyl was administered as an increasing stepwise infusion f...
Stover SM, Pool RR.Gentamicin sulfate (3 ml; 50 mg/ml) was administered intra-articularly into 30 normal equine radiocarpal joints after arthrocentesis. Arthrocentesis alone was performed on 10 normal radiocarpal joints. Synovial fluid evaluations and gross and microscopic examinations were performed on synovial fluid and synovial membrane of designated joints at selected daily intervals over a period of 10 days. Synovial fluid from gentamicin-injected joints had greater turbidity, higher RBC and WBC counts, and higher refractive indices than did joints not injected with gentamicin. The largest increases develop...
Corley KT.Successful treatment with inotropes and vasopressors depends on an understanding of the interplay of flow, pressure, and resistance in the cardiovascular system and an appreciation of the pathophysiologic mechanisms leading to inadequate tissue perfusion. Any treatment strategy is necessarily a compromise between the requirements of different vascular beds.Furthermore. the underlying hemodynamic derangements can change rapidly. Therefore. inotropes and vasopressors should be titrated to measures of improved hemodynamic status, and the treatments should be frequently reviewed.
Lloyd KC, Stover SM, Pascoe JR, Adams P.Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 X 10(6) colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (IA); group-2 horses (n = 5) each...
Knych HK, Steffey EP, Mama KR, Stanley SD.To verify the isoflurane anesthetic minimum alveolar concentration (MAC)-sparing effect of a previously administered target plasma fentanyl concentration of 16 ng/mL and characterize an anticipated further sparing in isoflurane MAC associated with higher target plasma fentanyl concentrations. Methods: 8 horses. Methods: Horses were assigned 2 of 3 target plasma fentanyl concentrations (16, 24, and 32 ng/mL), administered in ascending order. Following determination of baseline MAC, horses received a loading dose of fentanyl followed by a constant rate infusion; MAC determination was performed i...
Bäumer W, Herrling GM, Feige K.To test the efficacy of the recombinant tissue-type plasminogen activator (rt-PA) alteplase in horses, the thrombolytic effect was tested in in vitro generated equine thrombi. The extent of lysis was determined by measuring the decrease in thrombi weight over a period of 4 hours. In vivo pharmacokinetics of alteplase were determined in 6 healthy horses. A single dose (1 mg/kg) was applied via intravenous infusion over a period of 30 minutes Coagulation-related variables, blood count and clinical parameters were taken before the treatment and until 48 h after treatment. In addition, plasma rt-P...
Knych HK, Weiner D, Arthur RM, Baden R, McKemie DS, Kass PH.Corticosteroids are potent anti-inflammatory drugs and as such are commonly administered to performance and racehorses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics and effects on cortisol and inflammatory mediator concentrations, following intravenous and oral administration to 12 exercised horses. Horses received an intravenous administration of 40 mg of dexamethasone sodium phosphate and 20 mg of dexamethasone tablets with a 4 week washout in between administrations. Blood and urine samples were collected prior to and for up to...
Peroni DL, Stanley S, Kollias-Baker C, Robinson NE.Based on its efficacy for the treatment of human asthma, the corticosteroid prednisone is commonly used in horses for treatment of recurrent airway obstruction. However, recent studies have failed to show any benefit of prednisone tablets for the treatment of this condition. The purpose of this study was to determine why oral prednisone has poor efficacy for the treatment of heaves in horses. In a crossover study, 5 horses were given the following treatments: prednisone tablets, prednisone liquid, prednisolone tablets, prednisolone liquid and i.v. prednisolone sodium succinate (positive contro...
Stojan J.Highly efficient and rapid lead compound evaluation for estimation of inhibition parameters and type of inhibition is proposed. This is based on a single progress-curve measurement in the presence of each candidate compound, followed by the simultaneous analysis of all of these curves using the ENZO enzyme kinetics suite, which can be implemented as a web application. In the first step, all of the candidate ligands are tested as competitive inhibitors. Where the theoretical curves do not correspond to the experimental data, minimal additional measurements are added, with subsequent processing ...
Kamerling S, Weckman T, Donahoe J, Tobin T.Current opiate receptor theory suggests that kappa agonists should provide good analgesia without producing marked central nervous system stimulation. U-50,488H is an experimental narcotic analgesic that is a selective kappa agonist. In the present study, U-50,488H produced good analgesia in horses using both the skin twitch and hoof withdrawal reflex assays. Further, the analgesia was relatively long lasting (120 mins) compared to other mu-agonists tested in horses. The locomotor response to U-50,488H was less than observed with ethylketazocine and butorphanol, and has yielded the smallest lo...
