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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.
Efficacy and safety of mitomycin C as an agent to treat corneal scarring in horses using an in vitro model. Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in vitro model. Methods: An in vitro model of equine corneal fibroblast (ECF) developed was used. The ECF or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFbeta1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion...
Equine estrogens impair nitric oxide production and endothelial nitric oxide synthase transcription in human endothelial cells compared with the natural 17{beta}-estradiol. Conjugated equine estrogen therapy is the most common hormone replacement strategy used to treat postmenopausal women. However, the ability of an individual conjugated equine estrogen to modulate NO production and, therefore, to induce cardiovascular protection is largely unknown. The effects of equine and naturally occurring estrogens on NO generation were evaluated in human aortic endothelial cells by measuring in vivo NO production, as well as NO synthase (eNOS) activity and expression. The transcriptional activity on the eNOS gene was determined by the ability of estrogen receptors (alpha ...
Evaluation of the role of superoxide anions in endotoxin-induced impairment of beta-adrenoceptor-mediated vasodilation in equine digital veins. To investigate the role of superoxide anions in the lipopolysaccharide (LPS)-induced impairment of beta-adrenoceptor-mediated equine digital vein (EDV) vasodilation. Methods: EDVs isolated from forelimbs of 24 healthy adult horses. Methods: Endothelium-intact or endothelium-denuded EDV rings were incubated with or without LPS (10 microg/mL) of Escherichia coli (O55:B5) for 4 hours. Cumulative concentration-relaxation curves resulting from administration of isoprenaline, a nonselective beta-adrenoceptor agonist, or from administration of SR 58611A, a selective beta(3)-adrenoceptor agonist, were...
Serum thyroid hormone, insulin, glucose, triglycerides and protein concentrations in normal horses: association with topical dexamethasone usage. The aim of this study was to determine if topical application of dexamethasone affected the serum concentrations of thyroid hormones (triiodothyronine T(3) and thyroxine T(4)), glucose, triglycerides, total protein and insulin in normal horses. Ten horses were treated twice daily for 10 days with 50 g dexamethasone using an ointment formulation. Thyroid hormones and insulin were assayed using standard radioimmunoassay methods, while glucose, triglycerides and total protein were determined using a standard enzymatic method and the Biuret reaction, respectively. An increase in serum glucose and ...
In vivo priming and ex vivo activation of equine neutrophils in black walnut extract-induced equine laminitis is not attenuated by systemic lidocaine administration. Laminitis is a crippling disease of horses characterized by an inflammatory response in the tissue that suspends the axial skeleton within the hoof. Pain is a common feature of laminitic pathology and its management is an important component of the treatment regime for this disease. Systemic lidocaine administration is commonly utilized to manage pain in equine laminitis; however, the potential anti-inflammatory effects of this drug during the treatment of equine laminitis have not been investigated. Here, we sought to determine if lidocaine concentrations achieved in the plasma (therapeutic c...
Efficacy of oral prednisolone and dexamethasone in horses with recurrent airway obstruction in the presence of continuous antigen exposure. Orally administered prednisolone and dexamethasone are used commonly in the treatment of recurrent airway obstruction (RAO) in horses. However, the efficacy of prednisolone in improving pulmonary function during continuous antigen exposure has not been evaluated critically and there is little evidence supporting the efficacy of low-dose oral dexamethasone in the same conditions. Objective: Oral prednisolone and dexamethasone improve pulmonary function in RAO under conditions of continuous antigen exposure, and dexamethasone is more effective than prednisolone at commonly used dosages. Methods:...
The pharmacologic basis for the treatment of endocrinopathic laminitis. 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.
The relationship between digital perfusion pressure and hoof lamellar blood flow in isoflurane-anesthetized horses. Digital perfusion pressure (DPP) equals mean arterial pressure (MAP) at the hoof coronet minus digital interstitial pressure (DIP) within the hoof. To test whether lamellar blood flow (LBF) changes proportionately to DPP, anesthesia was induced and maintained with isoflurane in six horses to target a MAP of 60 mmHg. Arterial, venous, and hoof interstitial pressures were measured in each pelvic limb. LBF was measured using fluorescent microspheres during dobutamine infusions targeting either 60 (low), 80 (medium), or 100 (high) mmHg MAP. Following euthanasia, hoof lamina was collected for micro...
In vitro antimicrobial activity of gallium maltolate against virulent Rhodococcus equi. The objective of this study was to determine the in vitro antimicrobial activity of gallium maltolate (GaM) against Rhodococcus equi. A total of 98 virulent bacterial isolates from equine clinical cases were examined, of which 19 isolates were known to be resistant to macrolides and rifampin. Isolates were cultured with various concentrations of GaM and minimal inhibitory concentration (MIC) values were determined after 24 and 48 h. Both the MIC(50) and the MIC(90) after 24h of growth were 558 ng/mL (8 μM) and after 48 h of growth were 2230 ng/mL (32 μM). There were no apparent differences b...
Pharmacological studies of bronchial constriction inhibited by parasympatholytics and cilomilast using equine precision-cut lung slices. Equine precision cut lung slices (PCLS) were used to evaluate the ability of several pharmacologic compounds, parasympatholytics atropine, ipratropium, tiotropium and phosphodiesterase (PDE) 4-inhibitor cilomilast, to inhibit methacholine (MCh) induced bronchial constriction. The study war performed using vital lung samples from 20 horses, harvested immediately after euthanasia and lung examination.Tissue samples from the cranial, caudal and accessory lobe were taken for histological examination. Viability in PCLS of 250 +/- 20 microm was confirmed by observation of cilia movement and bronchia...
The efficacy of imiquimod 5% cream (Aldara® in the treatment of aural plaque in horses: a pilot open-label clinical trial. Aural plaques affect at least 22% of horses and can be asymptomatic or cause ear sensitivity. Immunohistochemical and electron microscopy studies have shown a strong association between aural plaques and papilloma virus. The purpose of this study was to investigate the efficacy of imiquimod 5% cream, an immune response modifier with potent antiviral activity, in the treatment of equine aural plaques. Twenty-one horses were enrolled and 16 completed the study. Imiquimod 5% cream was applied three times a week, every other week. When both ears were affected only the worst affected ear was treate...
Effect of intravenous lidocaine administration on laminar inflammation in the black walnut extract model of laminitis. Laminitis is a serious complication of horses suffering from sepsis/endotoxaemia-related events. Laminitis in horses and organ injury in human sepsis are both reported to involve inflammatory injury to the laminae/organs including early activation of endothelium and leucocytes leading to emigration of neutrophils into the tissue interstitium. In the black walnut extract (BWE) model, systemic inflammatory events coincide with marked increase in laminar mRNA concentrations of inflammatory genes including proinflammatory cytokines (i.e. IL-1beta, IL-6), COX-2, chemokines (i.e. IL-8) and endotheli...
Comparison of cardiovascular function and quality of recovery in isoflurane-anaesthetised horses administered a constant rate infusion of lidocaine or lidocaine and medetomidine during elective surgery. The effects of lidocaine combined with medetomidine or lidocaine alone on cardiovascular function during anaesthesia and their effects on recovery have not been thoroughly investigated in isoflurane-anaesthetised horses. Objective: To determine the effects of an intraoperative i.v. constant rate infusion of lidocaine combined with medetomidine (Group 1) or lidocaine (Group 2) alone on cardiovascular function and on the quality of recovery in 12 isoflurane-anaesthetised horses undergoing arthroscopy. Objective: The combination would depress cardiovascular function but improve the quality of rec...
Effect of an endurance-like exercise on the disposition and detection time of phenylbutazone and dexamethasone in the horse: application to medication control. Equine antidoping rules were established to prevent a horse's performance being altered after the administration of prohibited substances, including approved drugs used for legitimate treatment. Veterinarians have to advise owners or trainers on appropriate withholding times to guarantee that their horses may safely compete after drug administration. In order to propose tailored withdrawal times, several horse organisations released detection time (DT) values, for the main veterinary drugs used in horses. One of the possible limits to the information provided by published DTs in horses is the ...
A secondary isotope effect study of equine serum butyrylcholinesterase-catalyzed hydrolysis of acetylthiocholine. beta-Secondary deuterium isotope effects have been measured for equine serum butyrylcholinesterase-catalyzed hydrolysis of acetyl-L(3)-thiocholine (L=H or (2)H). The dependencies of initial rates on isotopic substrate concentrations show close adherence to Michaelis-Menten kinetics, and yield the following isotope effects: (D3)k(cat)/K(m)=0.98+/-0.02 and (D3)k(cat)=1.10+/-0.02. The modestly inverse isotope effect on k(cat)/K(m) is consistent with partial rate limitation by a step that converts the sp(2)-hybridized ester carbonyl of the E+A reactant state into a quasi-tetrahedral transition sta...
Focal skeletal muscle uptake of 99mTechnetium-hydroxymethylene diphosphonate following peroneal nerve blocks in horses. We have observed focal skeletal muscle uptake of 99mTechnetium-hydroxymethylene diphosphonate (Tc-HDP), which could mimic a tibial lesion, in horses following peroneal nerve blocks. To characterize this observation further, 45 bone phase scintigrams were performed in 12 horses undergoing peroneal nerve blocks. Scans were performed before, and 1, 3, 7, and 14 days postblock. The superficial and deep branches of the peroneal nerve were blocked by injecting 10 ml of 2% mepivacaine in one limb and 20 ml in the other. Images were evaluated for uptake at the block site and uptake likely to mimic a t...
On the search for in vitro in vivo correlations in the field of intra-articular drug delivery: administration of sodium diatrizoate to the horse. 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 ...
Determination of (13)C/(12)C ratios of urinary excreted boldenone and its main metabolite 5beta-androst-1-en-17beta-ol-3-one. Boldenone (androsta-1,4-dien-17beta-ol-3-one, Bo) is an anabolic steroid known to have been used in cattle breeding or equine sport as a doping agent for many years. Although not clinically approved for human application, Bo or its main metabolite 5beta-androst-1-en-17beta-ol-3-one (BM1) were detected in several doping control samples. For more than 15 years the possibility of endogenous Bo production in human beings has been discussed. This is a challenging issue for doping control laboratories as Bo belongs to the list of prohibited substances of the World Anti-Doping Agency and therefore th...
[Comparative efficacy of homologous and heterologous biologicals against diphtheria]. Comparative assessment of efficacy of homologous and heterologous diphtheria antitoxins on the example of diphtheria intoxication. Methods: Homologous hyperimmune sera were obtained through immunization of rabbits and guinea-pigs with diphtheria toxoid according to schedule. Immune rabbit sera contained 70 - 100 IU/mL of antitoxin antibodies and guinea-pig sera contained 60 - 80 IU/mL. Equine diphtheria antitoxin was used as a heterologous one. Measurement of antitoxin level using experimental animals is based on quantitative assessment of ability of studied sera to neutralize specific dermone...
Partial intravenous anaesthesia in 5 horses using ketamine, lidocaine, medetomidine and halothane. A partial intravenous protocol was used successfully to maintain anaesthesia in 5 healthy horses. Horses were premedicated with acepromazine, romifidine and butorphanol, induced with guaifenesin and ketamine and maintained on a constant rate infusion of lidocaine, ketamine and medetomidine together with halothane inhalation anaesthesia. Mean end-tidal halothane concentration to maintain a surgical plane of anaesthesia was 0.8 +/- 0.2%. Mean dobutamine requirement to maintain mean arterial pressure above 9.31 kPa was 0.42 +/- 0.3 microg/kg/min. The administration of relatively low doses of lido...
Tachypnea and antipyresis in febrile horses after sedation with alpha-agonists. Signs of tachypnea after sedation of febrile horses with alpha2-agonists have been noted previously but have not been further investigated. Objective: To examine the effects of xylazine and detomidine on respiratory rate and rectal temperature in febrile horses and to investigate if either drug would be less likely than the other to cause changes in these variables. Methods: Nine febrile horses and 9 healthy horses were included in the study. Methods: Horses were randomly assigned to sedation with xylazine 0.5 mg/kg or detomidine 0.01 mg/kg. Heart rate and respiratory rate were recorded before...
Concentrations of altrenogest in plasma of mares and foals and in allantoic and amniotic fluid at parturition. Treatment with the progestin altrenogest is widely used in pregnant mares. The fact that foals born from healthy mares treated with altrenogest until term suffered from neonatal problems raises the question of direct effects of altrenogest on vital functions in the neonate. We have therefore investigated altrenogest concentrations in maternal and neonatal blood plasma and in fetal fluids. Pregnant mares were treated with altrenogest orally once daily (0,088 mg/kg bodyweight, n = 7) or left untreated (n = 8) from 280 d of gestation until foaling. Altrenogest concentration was determined in plas...
In vivo administration of acepromazine or promethazine to horse decreases the reactive oxygen species production response of subsequently isolated neutrophils to stimulation with phorbol myristate acetate. The previous experiments have shown that some phenothiazines have antioxidant and anti-inflammatory properties in vitro. In this study the inhibition of the production of reactive oxygen species (ROS) by neutrophils was studied in two groups of horses, which received a dose of 0.1 mg/kg of either acepromazine or promethazine intravenously. Blood samples were collected before (T0) and 0.5, 1, 3 and 5 h after drug administration. The chemiluminescence (CML) response of neutrophils was measured ex vivo in the presence of luminol for a period of 10 min and the maximum CML value (peak value) record...
Distribution of voriconazole in seven body fluids of adult horses after repeated oral dosing. The purpose of this study was to assess safety and alterations in body fluid concentrations of voriconazole in normal horses on days 7 and 14 following once daily dose of 4 mg/kg of voriconazole orally for 14 days. Body fluid drug concentrations were determined by the use of high performance liquid chromatography (HPLC). On day 7, mean voriconazole concentrations of plasma, peritoneal, synovial and cerebrospinal fluids, aqueous humor, epithelial lining fluid (ELF), and urine were 1.47 +/- 0.63, 0.61 +/- 0.22, 0.70 +/- 0.20, 0.62 +/- 0.26, 0.55 +/- 0.32, 79.45 +/- 69.4, and 1.83 +/- 0.44 microg...
Aqueous humor and plasma concentrations of ciprofloxacin and moxifloxacin following topical ocular administration in ophthalmologically normal horses. To determine the degree of ocular penetration and systemic absorption of commercially available topical ophthalmic solutions of 0.3% ciprofloxacin and 0.5% moxifloxacin following repeated topical ocular administration in ophthalmologically normal horses. Methods: 7 healthy adult horses with clinically normal eyes as evaluated prior to each treatment. Methods: 6 horses were used for assessment of each antimicrobial, and 1 eye of each horse was treated with topically administered 0.3% ciprofloxacin or 0.5% moxifloxacin (n = 6 eyes/drug) every 4 hours for 7 doses. Anterior chamber paracentesis wa...
Evaluation of the effect of phosphodiesterase on equine platelet activation and the effect of antigen challenge on platelet phosphodiesterase activity in horses with recurrent airway obstruction. To determine whether expression of equine platelet activation-dependent surface markers is influenced by phospodiesterase (PDE) isoenzyme activity and whether antigen challenge alters platelet PDE activity in horses with recurrent airway obstruction (RAO). Methods: 16 horses. Methods: 7 healthy horses were used for in vitro experiments, 6 horses with RAO were used for antigen challenge, and 6 healthy horses were used as control animals. Three of the healthy horses had also been used in the in vitro experiments. Effects of PDE inhibition and activation of adenylyl cyclase on CD41/61 and CD62P e...
Administration of perioperative penicillin reduces postoperative serum amyloid A response in horses being castrated standing. To compare postoperative inflammatory responses in horses administered perioperative procaine penicillin and those not administered penicillin using acute phase protein serum amyloid A (SAA) as a marker of inflammation. Methods: Randomized clinical trial. Methods: Stallions (n=50) castrated under field conditions. Methods: SAA concentrations were determined on days 0, 3, and 8. Six horses were subsequently excluded because of elevated SAA concentrations on day 0. Of the remaining 50 horses, 26 were administered nonsteroidal anti-inflammatory drug (NSAID) therapy and 24 were administered NSAID ...
Are macrocyclic lactones useful drugs for the treatment of Parascaris equorum infections in foals? A study was carried out to assess the field efficacy of moxidectin (MOX) against Parascaris equorum in foals. A total of 70 foals from 2 Italian thoroughbred (Farms 1 and 2) stud farms and one trotter stud farm (Farm 3), aged 3-5 months and with faecal egg counts (FEC) f>or=300 eggs per gram (EPG) were included in the study. On each farm, foals were divided into 2 groups (of 10, 8 and 10 foals, respectively) and treated with either moxidectin (MOX, 400 mcg/kg b.w.) or ivermectin (IVM, 200 mcg/kg b.w.) on day 0 and examined for faecal count reduction (FECR) on day 14. Five, 4 and 5 foals, re...
Treatment efficacy of trimethoprim sulfamethoxazole, pentoxifylline and altrenogest in experimentally induced equine placentitis. The objective was to determine if long-term treatment with trimethoprim sulfamethoxazole (antimicrobial), pentoxifylline (anti-inflammatory/anti-cytokine) and altrenogest (synthetic progestin), would improve pregnancy outcome in mares with experimentally induced placentitis. Seventeen normal, pregnant pony mares were enrolled in the study at 280-295 d of pregnancy. Placentitis was induced in all mares by intra-cervical inoculation of Streptococcus equi subsp. zooepidemicus (10(7) CFU). Five mares served as infected, untreated control animals (Group UNTREAT). Twelve mares (Group TREAT) were inf...
