Pharmacology in horses involves the study and application of drugs and medications to diagnose, treat, and prevent diseases and conditions in equine species. This field encompasses the understanding of pharmacokinetics and pharmacodynamics specific to horses, including how drugs are absorbed, distributed, metabolized, and excreted by the equine body. Commonly studied pharmacological agents in horses include non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, sedatives, and anthelmintics. Research in equine pharmacology focuses on determining appropriate dosages, understanding drug interactions, and minimizing adverse effects. This page compiles peer-reviewed research studies and scholarly articles that investigate the efficacy, safety, and regulatory aspects of pharmacological interventions in equine veterinary practice.
Törneke K, Ingvast Larsson C, Appelgren LE.Beta2-adrenoceptor agonists are used as bronchodilators in both humans and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human asthma. Little is known of the properties of the latter two drugs in equine medicine. We have compared salbutamol and terbutaline with clenbuterol in relation to their ability to relax muscle strips from equine tracheal muscle, precontracted with 40 nM carbachol, in tissue chambers. The affinities of these drugs to the be...
Clegg PD, Jones MD, Carter SD.Loss of articular cartilage, which is the most important pathological lesion occurring in osteoarthritis, has been shown to be enzymatically mediated. The matrix metalloproteinases (MMPs) are a group of enzymes which have been implicated in this degradation of articular cartilage matrix. The use of pharmacological agents to inhibit this catabolic process in the joint is a potential route for therapeutic intervention. The gelatinase MMPs, MMPs-2 and 9, were purified by affinity chromatography from equine cell cultures. The ability of phenylbutazone, flunixin, betamethasone, dexamethasone, methy...
Ramirez S, Seahorn TL, Williams J.This report describes a renal ultrasonographic abnormality (medullary rim sign), which was identified in 2 separate cases of spontaneously occurring disease associated with chronic and acute overdosage of phenylbutazone therapy. In horses, medullary rim sign has only been documented in neonatal foals experimentally administered large doses of phenylbutazone.
Venugopalan CS, Moore RM, Holmes EP, Sedrish SA, Koch CE.1. The role of endothelium in modulating equine colonic vessel responses to histamine (HST), 5-hydroxytryptamine (5-HT), bradykinin (BK) and acetylcholine (ACh) was evaluated in vitro. 2. Segments of mesenteric arteries and veins were collected from the left ventral colon of six adult horses destined for euthanasia for reasons unrelated to cardiovascular or gastrointestinal systems. Vessels were gently cleansed and cut into 4 mm wide rings. 3. Three vessel conditions namely endothelium intact, endothelium removed and N omega-nitro-L-arginine methyl ester (L-NAME)-treated were used for both art...
Yudkowsky ML, Beech J, Fletcher JE.In equine hyperkalemic periodic paralysis (HyperPP), there is evidence suggesting that the primary defect in the sodium channel is associated with a secondary alteration in triacylglycerol-associated fatty acid metabolism (TAFAM) in skeletal muscle. Furthermore, TAFAM may be involved in the therapeutic action of phenytoin. The effects of phenytoin treatment on the transcript levels of three key proteins in TAFAM, hormone sensitive lipase (HSL), carnitine palmitoyltransferase (CPT), and fatty acid binding protein (FABP), were examined. These transcripts were quantitated by competitive reverse t...
Mama KR, Pascoe PJ, Steffey EP, Kollias-Baker C.To characterize responses associated with two 1-hour total intravenous anesthesia techniques in horses. Methods: 6 mature, healthy mares. Methods: Each horse was anesthetized 3 times. Treatment order was determined by a series of Latin squares. After baseline measurements and instrumentation, horses were given xylazine (XYL) i.v.; anesthesia was induced 5 minutes later with 10% guaifenesin given i.v., then either ketamine (KET) or propofol (PRO) was given i.v. After anesthesia induction, each horse received an infusion of XYL and either KET or a low or high dose of PRO. Cardiopulmonary variabl...
Davison LA, McManus CJ, Fitzgerald BP.In the mare, endogenous opioids have been implicated in the suppression of gonadotropin secretion during seasonal anestrus (AN). The present study tested whether continuation of reproductive activity during the nonbreeding season (NBS) reflects the absence of a seasonal shift in opioid tone compared to what occurs in AN mares. During the NBS, 11 AN and 8 luteal-phase mares received 0.1, 0.05, 0. 025 mg/kg naloxone (NAL) or vehicle on alternate days. Whereas cycling mares responded to all dosages of NAL, AN mares responded only to the higher dosages for FSH, and LH failed to increase at any dos...
Szöke MO, Blais D, Cuvelliez SG, Lavoie JP.To evaluate the cardiovascular and respiratory effects of buprenorphine administered intravenously in clinically normal horses and horses with chronic obstructive pulmonary disease (COPD). Methods: 5 clinically normal horses and 5 horses with COPD that were in partial clinical remission (period A) or were having an acute attack of airway obstruction (period B). Methods: Pulmonary function testing, arterial blood gas analysis, and arterial blood pressure measurements were performed before and after a single intravenous bolus of buprenorphine (3 microg/kg of body weight). Respiratory rate (f), t...
McClanahan S, Hunter J, Murphy M, Valberg S.Propylene glycol and mineral oil are commonly used in the veterinary profession for treatment of bovine ketosis and equine impactions, respectively. Accidental administration of 6.0 ml propylene glycol/kg of body weight in horses causes severe depression, ataxia and malodorous breath and feces. However, appropriate medical therapy can result in successful treatment of this toxicosis.
Krieger RI, South P, Mendez Trigo A, Flores I.Methomyl (S-methyl-N-((methylcarbamoyl)oxy) thioacetimidate) toxicity was studied in horses using i.v. dosages from 0.01 to 3.0 mg/kg. Doses of 1-3 mg methomyl/kg produced increased GI motility and respirations, facial fasiculations, salivation, lacrimation and convulsions. The only effect at 0.5 mg/kg was increased GI sounds in 1/4 horses. This extensively used crop insecticide had been associated with episodes of morbidity and mortality and led to speculation that it was extremely potent to the horse. This was not supported by these clinical studies.
Foster AP, McKelvie J, Cunningham FM.A whole-body extract of Culicoides impunctatus induced a biphasic increase in oedema formation in ponies with insect hypersensitivity, with maxima after one and eight hours. The Culicoides antigen did not induce similar responses in ponies with no previous history of the disease. In insect-hypersensitive ponies the local administration of chlorpheniramine (12 micrograms) completely inhibited oedema formation in response to histamine (0.04 microgram) and to Culicoides antigen (0.5 microgram) at one hour, and the response to Culicoides antigen at eight hours was inhibited by 63 per cent. Chlorph...
Bailey SR, Elliott J.5-hydroxytryptamine (5-HT) is a potent vasoconstrictor of equine digital arteries and veins which may play a role in the ischaemic disease, laminitis. The present investigation compared the properties of 5-HT1B/1D receptors in arteries with those in veins using isolated rings of equine digital blood vessels. The 5-HT1B/1D receptor-selective agonists, anpirtoline and sumatriptan were 17.9 and 10 times more potent and produced 4.1 and 5.6 times greater maximum contractions, respectively, in veins when compared to arteries. Other agonists tested were of equal potency and produced the same maximum...
Moore CP, Halenda RM, Grevan VL, Collins BK.Traumatic keratouveitis in horses is characterised by a unilateral, aseptic, vascularising keratitis accompanied by moderate to severe anterior uveitis. In a series of 9 cases of post traumatic keratouveitis, topical and systemic nonsteroidal drugs and atropine were used to control the anterior uveitis while allowing spontaneous corneal healing. Among the 9 cases reported, 6 affected eyes previously treated with local corticosteroids took significantly longer to resolve when compared to 3 eyes in which corticosteroids had not been administered. It was concluded that, in cases of equine post tr...
Heath MF, Evans RJ, Hayes LJ.Dextrans of mean molecular weight 70 kDa (dextran-70) have had clinical use as anti-thrombotics in man. A major part of the anti-thrombotic action is mediated via inhibition of platelet function. Greatorex (1975, 1977) treated thromboembolic colic in horses with infusions of dextran-70 and reported a 90% recovery rate, but this treatment is nonetheless rarely used. We have used an in vitro method to examine the effect of dextran-70 on equine platelet suspensions, in the hope that understanding the mechanism of action of dextran-70 might lead to the development of alternative therapeutic agents...
Matthews NS, Hartsfield SM, Mercer D, Beleau MH, MacKenthun A.To compare recovery from sevoflurane or isoflurane anesthesia in horses. Methods: Prospective, randomized cross-over design. Methods: Nine Arabian horses (3 mares, 3 geldings, and 3 stallions) weighing 318 to 409 kg, 4 to 20 years old. Methods: Horses were anesthetized on three occasions with xylazine (1.1 mg/kg), Diazepam (0.03 mg/kg intravenously [i.v.]), and ketamine (2.2 mg/kg i.v.). After intubation, they were maintained with isoflurane or sevoflurane for 90 minutes. On a third occasion, horses were maintained with sevoflurane and given xylazine (0.1 mg/kg i.v.) when the vaporizer was tur...
Rathbone MJ, Macmillan KL, Jöchle W, Boland MP, Inskeep EK.This paper describes the estrus cycles of a number of livestock breeds and reviews the controlled-release drug delivery systems that are currently available for the purpose of controlled breeding. The bovine estrus cycle is reviewed in detail, and the estrus cycles of other species are described in a manner that highlights similarities and differences between species. Pertinent formulation and pharmacokinetic information about current drug delivery systems is presented and discussed, and recent advances in this area are also described.
Smith G, Bertone AL, Kaeding C, Simmons EJ, Apostoles S.To evaluate the effect of topically applied dimethylsulfoxide (DMSO) on lipopolysaccharide (LPS)-induced synovitis in the mid-carpal joint. Methods: 6 sound, healthy, adult horses (12 carpi). Methods: In a double-blinded, crossover, paired study with a 1-week washout period, mid-carpal joints were allocated to group 1 (DMSO, n = 6) or group 2 (control, n = 6). Each joint was injected with 1.3 ml (0.0125 ng/dl) of LPS to induce synovitis. For group-1 joints, DMSO gel (15 g; 90%) was applied after injection of LPS and at 12-hour intervals for 60 hours. Joints of group 2 received LPS, but not DMS...
Heneine LG, Carvalho AD, Barbosa CF, Arávjo dos Santos MR.The objective of this study was the search for a suitable venom antigen to be used in an in vitro alternative immunoassay, to the standard antivenom neutralization assay using mice. Bothrops jararaca venom was fractionated in DEAE-Sephacel columns and the fractions were tested for a correlation between antibody capture enzyme linked immunosorbent assay (ELISA) absorbance values and the 'in vivo' antivenom potency. Individual antivenoms from 14 horses and 15 separate FUNED polyspecific Bothrops ampouled antivenoms (final product) were used. Fractions showing the higher correlations were further...
Maria WS, Cambuy MO, Costa JO, Velarde DT, Chávez-Olórtegui C.The correlation coefficients between in vivo neutralization of lethal toxicity (ED50), neutralization of the hemolytic activity (PLA2) and levels of antibodies measured by ELISA, was investigated to test the potency of horse anti-bothropic antivenom. Twenty six horses were hyperimmunized with Bothrops venoms (B. alternatus, B. jararaca, B. jararacussu, B. neuwiedii and B. moojeni). To set up an indirect ELISA, for neutralization of PLA2 activity and for determination of ED50 in Swiss mice, the whole Bothrops jararaca venom (reference venom for assessing the bothropic antivenom potency in Brazi...
Wittern C, Hendrickson DA, Trumble T, Wagner A.A 364-kg (800-lb) 15-month-old sexually intact cryptorchid male Quarter Horse was admitted to the veterinary teaching hospital for castration. The horse was placed in standing stocks, and a caudal epidural injection of 18 mg of detomidine hydrochloride (50 micrograms/kg [23 micrograms/lb] of body weight) was administered. Fifteen minutes after injection, the horse unexpectedly collapsed to the floor, first into sternal, and then into lateral, recumbency. Because the horse would not get up, the decision was made to perform the surgery with the horse under general anesthesia. The horse required ...
Rush BR, Flaminio MJ, Matson CJ, Hakala JE, Shuman W.To determine cytologic changes in horses with recurrent airway obstruction (heaves) after administration of aerosolized beclomethasone dipropionate and dexamethasone parenterally. Methods: 6 horses with inducible and reversible heaves. Methods: Episodes of heaves were induced by exposure to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone, parenterally administered dexamethasone, aerosolized propellant), and pulmonary inflammation was evaluated by serial cytologic examination of bronchoalveolar lavage (BAL) fluid samples obtained on days 0, 7...
Rush BR, Raub ES, Rhoads WS, Flaminio MJ, Matson CJ, Hakala JE, Gillespie JR.To determine changes in clinical signs of disease and response to pulmonary function testing in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. Methods: 6 horses with inducible and reversible heaves. Methods: Episodes of heaves were induced by exposure (challenge) to moldy hay and straw for 7 days. Horses were assigned to treatment groups (aerosolized beclomethasone dipropionate, parenterally administered dexamethasone, aerosolized propellant [control]), and respiratory frequency and s...
Rush BR, Worster AA, Flaminio MJ, Matson CJ, Hakala JE.To determine alteration in adrenocortical function in horses with recurrent airway obstruction (heaves) after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively. Methods: 6 horses with inducible and reversible heaves. Methods: Episodes of heaves were induced by exposure to moldy hay and straw for 7 days (natural challenge). Horses then underwent treatment (aerosolized beclomethasone, parenterally administered dexamethasone, and aerosolized propellant) for 7 days. Horses remained in the mold-contaminated environment for 7 days after discontinuat...
Doherty TJ, Frazier DL.This study investigated the effect of lidocaine i.v. on halothane minimum alveolar concentration (MAC) in ponies. Six ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure maintained within clinically acceptable limits. Following a 2 h equilibration period, baseline halothane MAC was determined. The ponies were then given a loading dose of lidocaine (2.5 or 5 mg/kg bwt) or saline over 5 min, followed by a constant infusion of lidocaine (50 or 100 microg/kg/min, or saline, respectively)....
Young LE, Blissitt KJ, Clutton RE, Molony V.To describe the haemodynamic effects of a 60 min infusion of dopamine 4 microg/kg bwt/min during halothane anaesthesia, 7 mature Thoroughbred horses were studied. The infusion began 1 h after induction of anaesthesia by romifidine (100 microg/kg) and ketamine (2.2 mg/kg bwt). Throughout the period of dopamine infusion and for 30 min after its discontinuation, the horses were ventilated by intermittent positive pressure to maintain PaCO2 between 4.6-5.4 KPa. Inspired halothane concentration was adjusted to maintain an end tidal halothane concentration of 0.9%. Haemodynamic variables were measur...
Harkins JD, Mundy GD, Stanley S, Woods WE, Sams RA, Richardson DR, Grambow SC, Tobin T.Isoxsuprine is reported to be a peripheral vasodilator used in human and veterinary medicine to treat ischaemic vascular disease. In horses, it is generally administered orally to treat navicular disease and other lower limb problems. To define the scope and duration of its pharmacological responses after oral administration, 6 horses were dosed with isoxsuprine HCl (1.2 mg/kg bwt) q. 12 h for 8 days and then tested to assess the duration and extent of pharmacological actions. There was no significant difference between isoxsuprine and control treatment values for heart rate, spontaneous activ...
Turner AS, Tucker CM.A randomised double-blind clinical trial of 28 horses was undertaken to evaluate the efficacy of isoxsuprine hydrochloride at four different doses:- 0.0 mg/kg bodyweight (bwt) (placebo), 0.6 mg/kg bwt, 1.2 mg/kg bwt and 1.8 mg/kg bwt for treatment of navicular disease. The results showed that horses treated with isoxsuprine hydrochloride (N = 22) responded significantly with respect to clinical assessment score (P less than 0.01) when compared with the control group (N = 6). Furthermore, there were no dose-related differences in the responses of the horses treated with increasing levels of iso...
Durham A.Although the treatment and management of laminitis in the horse requires a holistic and often multidisciplinary approach from the veterinarian, farrier, and nutritionist, this review focuses on pharmacologic interventions that might have prophylactic benefit, specifically in the horse with laminitis as a result of pituitary pars intermedia dysfunction and equine metabolic syndrome.
Sexton WL, Erickson HH.Cardiopulmonary responses of four ponies were monitored during standard exercise tests (SET), before and after beta-adrenergic receptor blockade with propranolol. The SET consisted of four 5 min increments of increasing speed from 1.0 to 2.8 m/sec on a treadmill at a 7 degrees incline. Data were collected at rest, throughout the SET and recovery. Administration of propranolol to ponies at rest had no effect on cardiopulmonary function. During the SET, increases in heart rate, mean pulmonary artery flow velocity (an index of cardiac output) and right ventricular dP/dt (an index of myocardial co...
Muir WW, Hamlin RL.The influence of breathing various concentrations of carbon dioxide and oxygen upon minute volume, tidal volume, and respiratory rate were examined in acetylpromazine-tranquilized horses. Responses in the horses before (control period) and after tranquilization were qualitatively similar to increases in carbon dioxide and to alterations in oxygen. The quantitative responses to these changes were less in tranquilized horses than in the same horses studied in the untranquilized state. Tranquilization had its most prominent effect upon respiratory rate in horses breathing room air.
Frost AB, Larsen F, Ostergaard J, Larsen SW, Lindegaard C, Hansen HR, Larsen C.Development of suitable in vitro release models for formulation development as well as quality control purposes has to be initiated in the early design phase of injectable depots. Optimally, construction of an in vitro release model may lead to the establishment of in vitro in vivo correlations. By using a model compound (sodium diatrizoate, DTZ), the purpose of this study was to investigate the possibility of establishing in vitro in vivo relations between the DTZ disappearance profile obtained from the donor compartment of the rotating dialysis cell model and the joint disappearance profile ...
Rose RJ, Kohnke JR, Baggot JD.Plasma phenylbutazone concentrations were determined for up to 12 h in 6 horses following intravenous and oral phenylbutazone administration. To evaluate the bioavailability of different oral preparations, phenylbutazone was administered in a paste as well as the traditional powder form. The effect of the state of stomach contents on the absorption of phenylbutazone was investigated by administering the paste before and after feeding; the powder was given in a small bran mash and a full feed of lucerne chaff, wheaten chaff and bran. Despite great variability among individual horses both the pa...
Lee YL, Clarke KW, Alibhai HI, Song DY.To evaluate the effect of ephedrine on intramuscular blood flow and hemodynamic parameters during equine anesthesia. Methods: Prospective experimental study. Methods: Six healthy adult Welsh Mountain ponies (five males, one female, mean weight: 267 kg, range: 213-347 kg). Methods: Halothane-anesthetized ponies received an IV bolus of ephedrine (0.1 mg kg), followed 30 minutes later by a second IV ephedrine injection (0.2 mg kg). Changes in intramuscular blood flows (IMBF) in upper and lower triceps brachii were measured by laser Doppler flowmetry. Cardiopulmonary measurements were made at inte...
Amann RP, Bowen JM, Pickett BW, Berndtson WE, Stashak RS, Voss JL.Twenty stallions were used to determine if the anthelmintic cambendazole affected seminal characteristics, spermatogenesis, concentration of testosterone in blood serum, or weights of the reproductive orgrans. With minor exceptions, significant differences were not found between values for 10 control and 10 stallions treated with a single oral dose (40 mg/kg body weight) of cambendazole. The treatment did not affect reproductive function and it was concluded that the drug should have no effect on the fertility of stallions.
Noll CV, Kilcoyne I, Nieto JE, Thio T, Byrne BA.To determine the ability of 0.2% polyhexamethylene biguanide (PHMB)-impregnated gauze to inhibit the growth of bacteria isolated from equine infected sites. Methods: In vitro study. Methods: Nine bacterial isolates were obtained from cultures submitted from equine patients presenting with penetrating injuries of the hoof (n = 4), septic osteitis (n = 1), synovial sepsis (n = 1), wounds (n = 2), and incisional infection following laparotomy (n = 1). Two standardized strains were also included. A standard inoculum of each isolate was placed on 12 Muller-Hinton agar plates. Squares (2.5 cm ×â€...
Koskinen E, Marttila P, Katila T.The long-term effects of the anabolic steroid 19-norandrostenololylaurate on semen characteristics of Finnhorse colts were studied in 3 experiments. Semen was collected initially at 24 months of age and then twice a year. In experiment I, 500 mg or 100 mg of steroid per animal was given every 3rd week from 12 or 16 months to 24 months of age. In colts treated with 500 mg of anabolic steroid every 3rd week, azoospermia was observed in 3 out of 5 colts in the first semen collections, immediately after the end of treatment. The other 2 colts had low sperm numbers and a high percentage of proximal...
Duncan JL, McBeath DG, Preston NK.The efficacy of a fenbendazole divided dose regime against immature stages of Trichonema spp, Strongylus vulgaris and Strongylus edentatus was evaluated. A group of 8 naturally infected 30 to 36-month-old ponies was divided into 2 equal groups on the basis of previous treatment and faecal egg counts, one group being treated with 7.5 mg/kg bwt of fenbendazole daily for 5 days. This treatment regime removed 80 per cent of migrating S vulgaris larvae, 100 per cent of migrating S edentatus larvae and 95 per cent of the mucosal stages of Trichonema spp. In addition, a virtual 100 per cent eliminati...
Asa CS, Ginther OJ.Dexamethasone, a synthetic glucocorticoid, was administered (30 mg/day) from Day 10 after ovulation to assess the involvement of the adrenal glands in the ovulatory cycle. Only 1 of 8 mares treated in this way exhibited behavioural oestrus, compared to 7 of 8 control mares. Mean maximum LH concentration and follicle size were significantly reduced. Ovulation occurred in 1 and possibly in 2 other treated mares, compared to all 8 control mares. The results demonstrated that dexamethasone can interfere with ovulation and associated events in the mare, but the mechanism of action is uncertain.
Rush BR, Hoskinson JJ, Davis EG, Matson CJ, Hakala JE.To determine whether pulmonary distribution of aerosolized technetium Tc 99m pentetate is improved after inhalation of a single dose of albuterol sulfate in horses susceptible to recurrent airway obstruction (heaves). Methods: 6 horses with heaves and 4 horses with normal respiratory tract function. Methods: Images were obtained during ventilation of horses at baseline (maximal change in pleural pressure during tidal breathing [deltaPpImax] >15 cm H2O) and after aerosolized albuterol sulfate (360 microg) administration, with a 24-hour washout period between experiments. The deltaPpImax was ...
Baker WT, Frederick J, Giguere S, Lynch TM, Lehmkuhl HD, Slone DE.To evaluate the outcome in horses treated with a rolling technique or surgically for nephrosplenic entrapment of the large colon (NSE) and to examine the benefit of phenylephrine (PE) HCl on the efficacy of nonsurgical (rolling) management of NSE. Methods: Case series. Methods: Horses (n = 211) diagnosed with NSE by rectal palpation with or without ultrasonography, or at the time of exploratory celiotomy or necropsy. Methods: Medical records (January 1, 2001-September 1, 2008) were collected from horses diagnosed with NSE at 2 referral centers. Records were used to obtain signalment, physical ...
Wilson SM, Gallagher M, Rakhit S, Remsbury AL, Ko WH.Uridine triphosphate (UTP) evoked inhibition of adrenaline-evoked cAMP accumulation in cultured equine epithelial cells (EC50, 1.8 +/- 0.2 microM) and this effect was mimicked by 5-Br-UTP (EC50, 6.6 +/- 1.8 microM) and uridine diphosphate (UDP; EC50, 96 +/- 26 microM). This inhibitory action of UTP was abolished by pre-treating cells with pertussis toxin (10 ng ml-1, 24 h). UTP (EC50, 2.3 +/- 0.3 microM) and 5-Br-UTP (EC50, 29.4 +/- 9.4 microM) also increased intracellular free calcium ([Ca2+]i) whilst UDP did not; the two effects are thus differentially sensitive to these pyrimidine nucleotid...