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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.
Effects of R and S enantiomers and a racemic mixture of carprofen on the production and release of proteoglycan and prostaglandin E2 from equine chondrocytes and cartilage explants. To examine effects of carprofen (enantiomers and a racemic mixture) on the metabolism of equine chondrocytes. Methods: Cartilage from clinically normal horses. Methods: Effects of carprofen on proteoglycan neosynthesis, glycosaminoglycan (GAG) release and prostaglandin (PG) E2 production by unstimulated chondrocyte monolayers and cartilage explants were examined, as were similar variables in monolayers and explants exposed to carprofen and recombinant human interleukin 1beta (IL-1). Carprofen (enantiomers and racemic mixture) was used alone or along with IL-1 on monolayers and explant cultures...
The cardiopulmonary effects of clenbuterol when administered to dorsally recumbent halothane-anaesthetised ponies–failure to increase arterial oxygenation. Clenbuterol (0.8 microg kg(-1) intravenously) was investigated in ponies (small horses) anaesthetised with acepromazine, detomidine and thiopentone, then halothane in oxygen alone (hyperoxic group) or with nitrous oxide (hypoxic group). Following instrumentation, ponies were placed in dorsal recumbency for 60 minutes, clenbuterol (both groups) or a saline control (hyperoxic group) given, and cardiopulmonary parameters monitored for a further 60 minutes. In the hyperoxic group, clenbuterol administration resulted in a transitory (<five minutes) 15 per cent fall in arterial blood pressure and...
Lidocaine in the horse: its pharmacological effects and their relationship to analytical findings. Lidocaine is a local anaesthetic agent that is widely used in equine medicine. It is also an Association of Racing Commissioners International (ARCI) Class 2 foreign substance that may cause regulators to impose substantial penalties if residues are identified in post race urine samples. Therefore, an analytical/pharmacological database was developed for this drug. Using our abaxial sesamoid local anaesthetic model, the highest no-effect dose (HNED) for the local anaesthetic effect of lidocaine was determined to be 4 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, administration...
Effects on the intramuscular blood flow and cardiopulmonary function of anaesthetised ponies of changing from halothane to isoflurane maintenance and vice versa. The effects on intramuscular blood flow and cardiopulmonary parameters of changing from anaesthesia with halothane to isoflurane and vice versa were investigated in six ponies (small horses). Anaesthesia was induced with xylazine, ketamine and diazepam, maintained for one hour with halothane at an end tidal concentration of 1 per cent and then with isoflurane at 1.5 per cent for a further hour (halo/iso). On another occasion the order in which the volatile agents were administered was reversed (iso/halo). After one hour of anaesthesia the mean (sd) arterial blood pressure (MAP) and cardiac out...
Conformationally restricted carbamate inhibitors of horse serum butyrylcholinesterase. Conformationally restricted carbamate inhibitors, exo-2-norbornyl-N-butylcarbamate (1), endo-2-norbornyl-N-butylcarbamate (2), l-adamantyl-N-butylcarbamate (3), and 2-adamantyl-N-butylcarbamate (4) as active site-directed irreversible inhibitors of horse serum butyrylcholinesterase are investigated for values of the dissociation constant (KI), the carbamylation constant (k2), and the bimolecular rate constant (ki). Compound 1 is the most potent inhibitor of the enzyme and the values of KI and ki are 20 nM and 1.1 x 10(5) M-1sec-1, respectively.
Effects of 6alpha-methylprednisolone acetate on an equine osteochondral fragment exercise model. To determine effects of intra-articularly administered 6alpha-methylprednisolone acetate (MPA) in exercised horses with carpal osteochondral fragmentation. Methods: 18 horses: 3 groups of 6 each. Methods: An osteochondral (chip) fragment was created in 1 randomly chosen middle carpal joint of each horse. Polyionic fluid (PF) was injected into both middle carpal joints of horses in the control group. In horses of the MPA-control group, MPA was injected into the middle carpal joint without an osteochondral fragment; a similar volume of PF was injected into the contralateral middle carpal joint. ...
Efficacy of a 2 per cent moxidectin gel against gastrointestinal parasites of ponies. The efficacy of moxidectin was evaluated in young ponies naturally infected with gastrointestinal parasites. Eight animals were treated orally with moxidectin at 0.4 mg/kg bodyweight and eight received only the vehicle. They were all necropsied two weeks later. Faecal samples were examined daily for egg counts and larval cultures. Parasites were recovered from total faecal samples collected daily and from the gastrointestinal tracts at necropsy. Moxidectin reduced the strongyle egg counts by > 99 per cent from three days after treatment but some individuals remained positive for 10 days. Th...
The application of electrocecography for evaluation of cecum motility in horses. Electrogastrography (EGG), in which the electrical activity of the smooth muscular layer of the stomach is recorded percutaneously through the abdominal wall, has been applied in recent years to humans as a non-invasive method. In acute abdominal disease in horses, it is considered diagnostically useful to analyze digestive activity using EGG. Electrocecography (ECG) was examined to determine its effectiveness in evaluating equine digestive motility through comparison, after xylazine administration, between the results of the percutaneous ECG method and the results obtained using a strain-gaug...
Relative binding of therapeutic drugs by sera of seven mammalian species. The relative binding of acetaminophen, lidocaine, phenobarbital, procainamide, quinidine, and theophylline to sera of seven mammalian species was studied. Pooled commercial sera from cow, goat, horse, human, pig, rabbit, and sheep were supplemented with 5 and 10 mM concentrations of each drug. For each serum, each drug, and each drug concentration, equilibrium dialysis was performed in duplicate against phosphate buffer (pH 7.4, 0.1 M, 4 degrees C). Percent drug bound to serum was calculated. Phenobarbital demonstrated more than 20% binding to goat, horse, human, and sheep serum at both 5 and ...
Characterisation of the cardiovascular pharmacology of medetomidine in the horse and sheep. Medetomidine was administered to sheep and horses at a dose rate of 5 microg kg(-1) (i.v.). Heart rate and blood pressure were recorded. Medetomidine induced bradycardia and a biphasic blood pressure response consisting of a transient hypertension followed by hypotension. Administration of prazosin (an alpha1 adrenoceptor antagonist; 100 microg kg(-1), i.v.) had no effect on the cardiovascular response to medetomidine (5 microg kg(-1), i.v.), but inhibited the cardiovascular response of methoxamine (an alpha1 adrenoceptor agonist; 75 microg kg(-1), i.v.). L-659,066 (an alpha2 adrenoceptor anta...
Pituitary-adrenocortical effects of methoxamine infusion on halothane anaesthetised ponies. This study investigated whether maintenance of normotension using a methoxamine infusion would prevent activation of the stress response during halothane anaesthesia in ponies. After acepromazine premedication, anaesthesia was induced with thiopentone in six ponies, and maintained for 120 minutes with halothane in oxygen and ventilation to normocapnia. Methoxamine (M, 0.013+/-0.005 mg kg(-1) min(-1)) or saline (C) was infused throughout anaesthesia. Sequential blood samples were taken for cortisol and ACTH assay. During anaesthesia normotension (mean arterial blood pressure 101-124 mm Hg) was ...
Effects of dopamine, dobutamine, dopexamine, phenylephrine, and saline solution on intramuscular blood flow and other cardiopulmonary variables in halothane-anesthetized ponies. To evaluate the effect on intramuscular blood flow (IMBF) and hemodynamic variables of 4 antihypotensive agents given during anesthesia. Methods: 8 ponies. Methods: Halothane-anesthetized ponies (n = 6) positioned in lateral recumbency received, on separate occasions, infusions of each of the following 4 agents in serially increasing dosages or saline solution: phenylephrine hydrochloride (0.25, 0.5, 1, and 2 microg/kg of body weight), dopamine (2.5, 5, 10, and 20 microg/kg), dobutamine (1, 2.5, 5, and 10 microg/kg), and dopexamine (0.5, 1, 5, and 10 microg/kg). Changes in IMBF (by laser-Doppl...
Normal variation in, and effect of 2% pilocarpine on, intraocular pressure and pupil size in female horses. To determine normal variation in, and effect of 2% pilocarpine hydrochloride on, intraocular pressure (IOP) and pupil size in female horses during a specified period. Methods: 10 female horses with normotensive eyes. Methods: IOP and horizontal and vertical pupil size were measured on a single day between 8 AM and 8 PM at hours 0, 0.5, 1, 2, 4, 6, 8, 10, and 12. Measurements were repeated after single- dose application of 2% pilocarpine to both eyes. IOP and pupil size were measured at 8 AM and noon in a 5-day experiment of twice-daily application of 2% pilocarpine. Results: Variation in IOP a...
Characterization of the antinociceptive and sedative effect of amitraz in horses. Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including alpha2-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of alpha2-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure...
A comparison between clenbuterol, salbutamol and terbutaline in relation to receptor binding and in vitro relaxation of equine tracheal muscle. 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...
The effect of drugs commonly used in the treatment of equine articular disorders on the activity of equine matrix metalloproteinase-2 and 9. 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...
Renal medullary rim sign in 2 adult quarter horses. 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.
Biphasic responses of equine colonic vessel rings to vasoactive inflammatory mediators. 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...
Phenytoin alters transcript levels of hormone-sensitive lipase in muscle from horses with hyperkalemic periodic paralysis. 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...
Comparison of two techniques for total intravenous anesthesia in horses. 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...
Gonadotropin response to naloxone in the mare: effect of time of year and reproductive status. 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...
Effects of buprenorphine on cardiovascular and pulmonary function in clinically normal horses and horses with chronic obstructive pulmonary disease. 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...
Propylene glycol toxicosis in a mare. 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.
Toxicity of methomyl following intravenous administration in the horse. 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.
Inhibition of antigen-induced cutaneous responses of ponies with insect hypersensitivity by the histamine-1 receptor antagonist chlorpheniramine. 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...
Evidence for different 5-HT1B/1D receptors mediating vasoconstriction of equine digital arteries and veins. 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...
