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Topic:Pharmacology
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.
Use of viscoelastic coagulation testing to monitor low molecular weight heparin administration to healthy horses. To evaluate the utility of thromboelastography (TEG) and Sonoclot analyses to monitor the effects of low molecular weight heparin (LMWH) administration to healthy horses. Methods: Randomized crossover study. Methods: Large animal veterinary teaching hospital. Methods: Six adult mixed breed healthy mares. Methods: LMWH (dalteparin) was administered (50 U/kg subcutaneously) either every 12 or 24 h for 3 consecutive days. Blood samples were collected before LMWH administration and then at selected time points for analysis. Thromboelastography derived R-time (R), K-time (K), angle (ANG), and maxim...
The effect of 1% tropicamide-induced mydriasis and cycloplegia on spherical refraction of the adult horse. 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 ...
On the repair of oxidative damage to apoferritin: a model study with the flavonoids quercetin and rutin in aerated and deaerated solutions. Ferritin (Ft) impairment through (•)O2(-), H2O2, and (•)OH production occurs in the cases of ketoses, diabetes mellitus, acute intermittent porphyria and tyrosinemia. In addition to (•)Trp and TyrO(•) radical production, ferrous iron liberation and Ft synthesis stimulation, site-specific oxidation reactions are induced leading to toxic iron accumulation in organs with high Ft content, for example, liver and brain. To elucidate the potential pathways to Ft recovery, repair of oxidative damage to horse spleen apoferritin (apoFt) and Ft by quercetin (QH) or rutin (RH) was studied in the p...
In vitro effects of three formulations of hydroxyethyl starch solutions on coagulation and platelet function in horses. To investigate the in vitro effects of 3 hydroxyethyl starch (HES) solutions on viscoelastic coagulation testing and platelet function in horses. Methods: Blood samples collected from 7 healthy adult horses. Methods: Blood samples were diluted with various crystalloid and HES solutions to approximate the dilution of blood in vivo that occurs with administration of a 10 and 20 mL/kg fluid bolus to a horse (1:8 and 1:4 dilutions, respectively). Diluted samples were analyzed through optical platelet aggregometry, platelet function analysis, thromboelastography, and dynamic viscoelastic coagulomet...
Identification of α-cobratoxin in equine plasma by LC-MS/MS for doping control. Cobra venom (Naja kaouthia) contains a toxin called α-cobratoxin (α-Cbtx). This toxin is a natural protein containing 71 amino acids (MW 7821 Da) with a reported analgesic potency greater than morphine. In 2007, in USA, this substance was found in the barns of a thoroughbred trainer and since then till date, the lack of a detection of this molecule has remained a recurring problem for the horseracing industry worldwide. To solve this problem, the first method for the detection of α-cobratoxin in equine plasma has now been developed. Plasma sample (3 mL) was treated with ammonium sulfate at ...
Effect of ephedrine and phenylephrine on cardiopulmonary parameters in horses undergoing elective surgery. To assess the cardiopulmonary effects of ephedrine and phenylephrine for management of isoflurane-induced hypotension in horses. Methods: Prospective randomized clinical study. Methods: Fourteen isoflurane-anesthetized horses undergoing digital palmar neurectomy. Methods: Ephedrine (EPH group; 0.02 mg kg(-1) minute(-1); n = 7) or phenylephrine (PHE group; 0.002 mg kg(-1) minute(-1); n = 7) was administered to all horses when mean arterial pressure (MAP) was <60 mmHg. The infusions were ended when the target MAP was achieved, corresponding to a 50% increase over the pre-infusion MAP (baseline)....
Oxytocin stimulated release of PGF2α and its inhibition by a cyclooxygenase inhibitor and an oxytocin receptor antagonist from equine endometrial cultures. Uterine inflammation results in a poor uterine environment and early embryonic loss in the mare due to an inhibition of maternal recognition of pregnancy caused from increased prostaglandin F2α (PGF2α). Oxytocin binds to endometrial cell receptors to activate prostaglandin synthesis. An oxytocin receptor antagonist (Atosiban) and a cyclooxygenase inhibitor (indomethacin) both decrease PGF2α production. The aim of this study was to evaluate the in vitro effects of Atosiban and indomethacin on equine uterine prostaglandin secretion. Equine endometrial explants were harvested on day two of beh...
Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses. Metformin is a potential therapeutic agent for the treatment of insulin resistance (IR). In laboratory animals, orally administered metformin reduces intestinal glucose absorption and may therefore affect insulinaemic responses to oral carbohydrate ingestion. Objective: To determine whether pretreatment with metformin reduces plasma glucose concentration and insulin responses following consumption of dextrose in horses. Methods: Therapeutic cross-over study. Methods: Seven healthy Standardbred and Thoroughbred geldings were subjected to an oral dextrose challenge test on 4 occasions: with and ...
The effects of pulse-delivered inhaled nitric oxide on arterial oxygenation, ventilation-perfusion distribution and plasma endothelin-1 concentration in laterally recumbent isoflurane-anaesthetized horses. Anaesthetized horses commonly become hypoxaemic due to ventilation/perfusion (V·A/Q·) mismatch and increased pulmonary shunt fraction (Qs·/Qt·). Pulse-delivered inhaled nitric oxide may improve oxygenation but may increase plasma concentration of the potent vasoconstrictor, endothelin-1 (ET-1). Objectives: Study 1) compare arterial oxygen concentration (PaO2) and saturation (SaO2), calculated Qs·/Qt· and ET-1 concentration; and Study 2) assess V·A/Q· matching and measured Qs·/Qt· in isoflurane-anaesthetized horses in left lateral recumbency receiving pulse-delivered inhaled nitric ox...
The role of polyphosphates in the sequestration of matrix metalloproteinases. This study outlines the potential of a novel therapeutic dressing for the management of chronic wounds. The dressing incorporates polyphosphate, a non toxic compound with a number of beneficial characteristics in terms of wound healing, in a foam matrix. The aim of this study was to identify the potential of polyphosphate incorporated in the foam dressing to sequester the activity of matrix metalloproteinases (MMPs) and proteases derived from Pseudomonas aeruginosa. Methods used included gelatin zymography and milk-casein agar plate analysis. Results have shown that this dressing is effectivel...
Comparison of phenylephrine administration and exercise versus phenylephrine administration and a rolling procedure for the correction of nephrosplenic entrapment of the large colon in horses: 88 cases (2004-2010). To compare the outcome of horses with nephrosplenic entrapment of the large colon (NSELC) that were treated nonsurgically by IV administration of phenylephrine and exercise with that of horses treated by IV administration of phenylephrine and a rolling procedure under general anesthesia. Methods: Retrospective case series. Methods: 88 horses with NSELC. Methods: Horses examined between 2004 and 2010 because of acute abdominal pain that had NSELC on the basis of findings on abdominal palpation per rectum, abdominal ultrasonography, or both were included. Medical records were reviewed to obtain ...
Endocrine evaluation after an intra-articular therapeutic dosage of dexamethasone in horses. This study investigated whether a single intra-articular administration (IA) of dexamethasone (DEX) in horses at therapeutic dosage could exert a systemic effect by influencing the hypothalamic-pituitary-adrenal axis activity as a consequence of (limited) absorption and systemic distribution. The results indicated that DEX was detectable in urine collected 12-48 h after IA administration and that injection was accompanied by a reduced urine excretion of cortisol, 6β-hydroxycortisol (6βOHF) and two other metabolites of cortisol lasting up to 48 h post-DEX administration. The systemic effect...
In vivo and in vitro effects of neostigmine on gastrointestinal tract motility of horses. To determine the response to neostigmine of the contractile activity of the jejunum and pelvic flexure and the effects of a continuous rate infusion (CRI) of neostigmine in horses. Methods: 7 adult horses and tissue from 12 adult horses. Methods: A CRI of neostigmine (0.008 mg/kg/h) or placebo was administered to 6 horses in a crossover study design. Gastric emptying was evaluated by the acetaminophen test. The frequency of defecation and urination and the consistency and weight of feces were recorded throughout the experiment. The effect of neostigmine on smooth muscle contractile activity wa...
Effect of selenium and vitamin C on clinical outcomes, trace element status, and antioxidant enzyme activity in horses with acute and chronic lower airway disease. A randomized clinical trial. Excess production of reactive oxygen species is involved in the pathogenesis of airway disorders in horses. Trace element antioxidants have a beneficial role in oxidant/antioxidant balance. The aim of the present study was to evaluate the effect of a combination of sodium selenite and ascorbic acid on clinical outcome, antioxidant enzymes, and trace elements status in horses with lower airway disease. For this purpose, 40 draft horses with lower airway disease were randomly selected (acute, n = 20; chronic, n = 20). Both acute and chronic cases were randomly allocated into two subgroup...
Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. A 4-year old, 500 kg Thoroughbred female horse diagnosed with bilateral forelimb laminitis and cellulitis on the left forelimb became severely painful and refractory to non-steroidal anti-inflammatory therapy (flunixin meglumine on days 1, 2, 3 and 4; and phenylbutazone on days 5, 6 and 7) alone or in combination with gabapentin (days 6 and 7). Methods: Pain scores assessed independently by three individuals with a visual analog scale (VAS; 0 = no pain and 10 = worst possible pain) were 8.5 on day 6, and it increased to 9.5 on day 7. Non-invasive blood pressure monitoring revealed severe hyper...
Comparison of glycopyrrolate and atropine in ameliorating the adverse effects of imidocarb dipropionate in horses. Imidocarb, an effective treatment for piroplasmosis, may cause colic and diarrhoea in horses. Atropine and glycopyrrolate are anticholinergics that could reduce the adverse effects of imidocarb. However, atropine and glycopyrrolate inhibit gastrointestinal motility, potentially causing ileus and colic. Objective: To compare glycopyrrolate and atropine in ameliorating the adverse effects of imidocarb dipropionate in horses and to determine the effect of combinations of these drugs on the gastrointestinal tract. Methods: A blinded, randomised, crossover study was performed in 8 healthy horses. E...
The addition of ticarcillin-clavulanic acid to INRA 96 extender for stallion semen cooling. A commonly used commercial extender (i.e. INRA 96) contains antimicrobials that may have limited effectiveness. Therefore, addition of ticarcillin-clavulanic acid to this extender is a widespread procedure in the equine breeding industry in the United States. However, such practice has not been critically evaluated. Objective: To evaluate the addition of ticarcillin-clavulanic acid to INRA 96 and different extender and antimicrobial storage conditions on sperm function and antimicrobial effectiveness. Methods: Gel-free semen (42 ejaculates from 14 mature Quarter Horse stallions) was extended w...
Effects of repeated intra-articular administration of amikacin on serum amyloid A, total protein and nucleated cell count in synovial fluid from healthy horses. Serum amyloid A (SAA) in synovial fluid has recently been used as a marker for septic arthritis in horses but the effects of repeated intra-articular (IA) administration of amikacin on synovial SAA concentrations are unknown. Objective: To report the effect of repeated IA administration of amikacin on SAA, total protein (TP), nucleated cell count (NCC) and differential NCC in synovial fluid of healthy equine joints. Methods: A controlled, 2 period crossover study was performed on 5 clinically healthy horses. Each intercarpal joint received one of 2 treatments every 48 h for 5 consecutive times...
Equine piroplasmosis treatment protocols: specific effect on orocaecal transit time as measured by the lactose 13C-ureide breath test. Imidocarb dipropionate is the drug of choice for equine piroplasmosis but its administration causes severe colic and diarrhoea. An imidocarb protocol that reduces these effects is needed. Objective: 1) Quantification of the effects of imidocarb dipropionate on equine orocaecal transit time (OCTT), with and without atropine or glycopyrrolate premedication and 2) investigation of an improved pretreatment regimen for imidocarb administration. Objective: Treatment with imidocarb dipropionate will result in colic and reduced OCTT as demonstrated by the lactose 13C-ureide breath test which will be a...
Dose titration of the clinical efficacy of intravenously administered flunixin meglumine in a reversible model of equine foot lameness. There are no refereed controlled documentations of the skeletal analgesic efficacy of different dosages of flunixin meglumine (FM). Objective: The objective of this experiment was to compare the efficacy of various dosages of FM with a negative control. The hypothesis was that higher doses would result in improved efficacy in a dose-dependent manner when tested in a reversible model of foot lameness. Methods: Ten horses shod with adjustable heart bar shoes had weekly modified AAEP grade 4.0/5.0 lameness induced by tightening a set screw against the heart bar. Heart rate (HR) and lameness score...
Effect of ketoprofen treatment on the uterine inflammatory response after AI of jennies with frozen semen. Artificial insemination (AI) involving the placing of frozen-thawed semen directly into the jenny uterine body is associated with very low pregnancy rates. This might be because of an exacerbation of the acute response of the endometrium to sperm, as seen in mares with persistent induced mating endometritis. Pregnancy rates can be increased in such mares, however, by including anti-inflammatory treatments in the insemination protocol (Bucca S, Carli A, Buckley T, Dolci G, Fogarty U. The use of dexamethasone administered to mares at breeding time in the modulation of persistent mating induced e...
Plasma matrix metalloproteinase activity in horses after intravenous infusion of lipopolysaccharide and treatment with matrix metalloproteinase inhibitors. To establish an in vivo method for matrix metalloproteinase (MMP)-2 and MMP-9 induction in horses via IV administration of lipopolysaccharide (LPS) and to evaluate the ability of doxycycline, oxytetracycline, flunixin meglumine, and pentoxifylline to inhibit equine MMP-2 and MMP-9 production. Methods: 29 adult horses of various ages and breeds and either sex. Methods: In part 1, horses received an IV administration of LPS (n = 5) or saline (0.9% NaCl) solution (5). Venous blood samples were collected before and at specified times for 24 hours after infusion. Plasma was harvested and analyzed f...
Comparison of efficacy and duration of effect on corneal sensitivity among anesthetic agents following ocular administration in clinically normal horses. 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...
Effects of imidazoline and nonimidazoline alpha-adrenergic agents, including xylazine, medetomidine, yohimbine, tolazoline, and atipamezole, on aggregation of bovine and equine platelets. 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...
Effects of oral clenbuterol on the clinical and inflammatory response to endotoxaemia in the horse. Pro-inflammatory cytokines, such as IL-1β and TNFα, play a major role in activating leukocytes and endothelial cells during the systemic inflammatory response to endotoxin in the horse. β2 agonist drugs, such as clenbuterol, inhibit leukocyte activation. This study aimed to determine the effects of oral clenbuterol on clinical and leukocyte responses, including production of TNFα, in an in vivo endotoxin challenge model. In a randomised crossover design, horses received either clenbuterol or a placebo product prior to the administration of low dose endotoxin (30 ng/kg over 30 min). Clinica...
Hemodynamic effects of 6% hydroxyethyl starch infusion in sevoflurane-anesthetized thoroughbred horses. To determine hemodynamic effects of hydroxyethyl starch (HES) infusion during anesthesia in horses, incremental doses of 6% HES were administered to 6 healthy Thoroughbred horses. Anesthesia was induced with xylazine, guaifenesin and thiopental and maintained with sevoflurane at 2.8% of end-tidal concentration in all horses. The horses were positioned in right lateral recumbency and administered 3 intravenous dose of 6% HES (5 ml/kg) over 15 min with 15-min intervals in addition to constant infusion of lactated Ringer's solution at 10 ml/kg/hr. Hemodynamic parameters were measured before and e...
General anesthesia in horses on fluid and electrolyte therapy. The purpose of this article is to update the community of veterinarians performing general anesthesia in horses on fluid therapy. The rationale behind intraoperative fluid therapy, fluid dynamics, and various fluid options (crystalloids, hypertonic saline, colloids) is discussed. Additionally, electrolytes (calcium, potassium, and sodium) are included in the discussion in relation to general anesthesia and intraoperative fluid management.
Influence of detomidine and xylazine on spleen dimensions and on splenic response to epinephrine infusion in healthy adult horses. To compare the changes in splenic length and thickness and in packed cell volume (PCV) following detomidine or xylazine administration and subsequent epinephrine infusion. Objective: Spleen relaxation occurs following xylazine or detomidine administration and interferes with subsequent splenic contractile response to epinephrine. Methods: Randomized non-blinded crossover experimental study. Methods: 6 healthy adult mares. Methods: The mares received an intravenous (IV) epinephrine infusion (1 μg kg(-1 ) minute(-1) over 5 minutes) one hour after IV administration of detomidine (0.01 mg kg(-1) ...
Seasonal variation in maintenance of phenylephrine-induced tone in isolated equine digital arteries under hypoxic or hyperoxic conditions in vitro. Digital vasoconstriction, ischaemia and hypoxia may predispose to acute laminitis. Laminitis incidence varies seasonally, peaking in spring and summer. Direct seasonal influences on equine digital artery (EDA) contractility have not been investigated. This study assessed seasonal variation in maintenance of phenylephrine (PHE)-induced tone in isolated EDAs under hypoxic (95% nitrogen) and hyperoxic (95% oxygen) conditions. The objective was to measure change in arterial tone over time after constriction to a plateau with PHE. Tone was measured at plateau and over time and percentage change cal...
Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites. Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be t...
