Topic:Opioids
Opioids in horses refer to a class of drugs that interact with opioid receptors in the central nervous system to produce analgesic effects. These substances are used in veterinary medicine for pain management, sedation, and anesthesia in equine patients. Opioids such as morphine, butorphanol, and buprenorphine are commonly administered to horses to alleviate pain associated with surgical procedures, injury, or chronic conditions. The pharmacokinetics and pharmacodynamics of opioids in horses can vary, influencing their efficacy and safety profiles. This topic includes a collection of peer-reviewed research studies and scholarly articles that explore the use, effects, and considerations of opioid administration in equine veterinary practice.
Cortisol, peptides and catecholamines in cerebrospinal fluid, pituitary effluent and peripheral blood of ponies. Cannulation of the pituitary effluent in horses is a useful method for investigating the release of pituitary hormones in loco (Irvine and Alexander 1987). Adrenocorticotropic hormone (ACTH) and arginine vasopression (AVP) concentrations in plasma collected from the intercavemous sinus, which receives all the pituitary outflow, were several times greater than those measured in peripheral plasma (Redekopp et at 1986). However, no studies evaluating the pituitary contribution to endogenous opioid secretion have been reported in the equine species. Cerebrospinal fluid (CSF) directly reflects CNS ...
Is the thoroughbred race-horse under chronic stress? Thoroughbred fillies were divided into three groups according to age: group 1, 7 fillies aged 1 to 2 years (G1) starting the training program; group 2, 9 fillies aged 2 to 3 years (G2) in a full training program; group 3, 8 older fillies 3 to 4 years of age (G3) training and racing. Blood samples were collected weekly from July to December. Cortisol was quantified using a solid phase DPC kit. The intra- and interassay coefficients of variation were 12.5% and 15.65% and sensitivity was 1.9 +/- 0.2 nmol/l. The semester average of cortisol levels varied between groups: G1 = 148.8 +/- 6.7, G2 = 12...
Influence of melatonin and oestradiol on the opioidergic regulation of LH and prolactin release in pony mares. The aim of this study was to investigate the influence of oestradiol, melatonin and season on the opioid regulation of LH and prolactin release. Effects of the opioid antagonist naloxone (0.5 mg/kg) on LH and prolactin secretion were determined in ovariectomized pony mares. In experiment 1, mares in January (n = 6) were pretreated with oestradiol benzoate (5 micrograms/kg) for 20 days. In experiment 2, beginning in May, mares (n = 7) received melatonin (15 mg) for 15 days and subsequently a combination of melatonin plus oestradiol for 20 days. In experiment 3, beginning in May, mares (n = 6) w...
Effects of alfentanil on the equine electroencephalogram during anaesthesia with halothane in oxygen. Opioids have variable effects on the minimum alveolar concentration of inhaled anaesthetics in the horse. During halothane anaesthesia at an end-tidal halothane concentration between 0.75 and 0.85 percent, the electroencephalogram (EEG) frequency power spectrum and the auditory evoked potential were recorded continuously in eight ponies during an infusion of approximately 40 micrograms kg-1 alfentanil over five minutes, and for a further 55 minutes. The spectral edge and median frequency of the EEG and the mid-latency of the auditory evoked potential at the time of maximum change of these vari...
Consideration of the relevance of ethological animal models for human repetitive behavioral spectrum disorders. Treatment successes of various stereotyped behaviors in animals and humans has renewed interest in ethologic animal models for the study of psychiatric disorders. This report presents another such behavior occurring in horses to weaving. This anomalous, repetitive, and purposeless behavior draws analogies to human compulsive spectrum behaviors. A "weaver" provided an opportunity to evaluate serotonin, dopamine, and opioid neurotransmitter system contributions by probing each with a selective agent in A-B-A-C-A-D design. The horse was treated in sequential 1-month periods separated by 1-month w...
Intra-articular morphine and saline injections induce release of large molecular weight proteoglycans into equine synovial fluid. Both morphine and physiologic saline injected intra-articularly into healthy equine tarsocrural joints induced a release of large molecular size proteoglycan (PG) subunits into the synovial fluid (SF) analysed 24 h postinjection. High-performance liquid chromatography (HPLC) with a size-exclusion column was used to assess the high molecular weight proteoglycans in equine synovial fluid (SF). The PG peaks of SF samples eluated separately from SF hyaluronate and other molecular components of the SF in the HPLC chromatographies indicating no interaction between hyaluronate and PG in the SF. Indiv...
Dynamics of the regulation of the hypothalamo-pituitary-adrenal (HPA) axis determined using a nonsurgical method for collecting pituitary venous blood from horses. Since 1985, we have applied our nonsurgical technique for collecting pituitary venous (PitVen) blood from ambulatory horses to investigate the regulation of adrenocorticotropic hormone (ACTH) secretion. This method offers particular advantages for studying the hypothalamo-pituitary-adrenal axis since its benign nature enables hypothalamic and pituitary interactions to be monitored without disturbing the animal, and the horse's large blood volume allows 3- to 4-ml samples to be collected as frequently as every 20s for prolonged periods so that the secretion patterns of ACTH and its secretagogue...
Establishing the cut-off concentration for the detection of etorphine in horse urine. An 125I radioimmunoassay to determine the pattern of urinary excretion of etorphine (a semisynthetic opiate agonist) after its administration to horses is described. Three thoroughbred horses were each given 5, 15, 30 and 100 micrograms of etorphine intramuscularly. Urine was collected for up to 72 after administration. The maximum etorphine concentration after administration of a dose of 5 micrograms was 711 pg ml-1 (concentrations were greater than 100 pg ml-1 after 23 h in all three horses); a 15 micrograms gave 2661 pg ml-1 (levels remained above 100 pg ml-1 for more than 44 h in each hors...
Drugs coordinating and restoring gastrointestinal motility and their effect on selected hypodynamic gastrointestinal disorders in horses and cattle. Hypodynamic gastrointestinal disorders in horses and cattle that are thought to benefit from treatment with drugs restoring and coordinating gastrointestinal motility include postoperative ileus and large colon impaction in the horse and displacement of the abomasum and dilatation of the cecum in cattle. Important physiologic, pathophysiologic and pharmacologic mechanisms involved in the intrinsic control of gastrointestinal motility include cholinergic, adrenergic, dopaminergic, serotoninergic, and opioid-mediated pathways. Preliminary results suggest that cisapride, acting on 5-Hydroxytrypta...
The effect of naloxone administration on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin in unperturbed horses. We used our nonsurgical method for collecting equine pituitary venous blood to study the role of endogenous opioids in the basal regulation of the hypothalamo-pituitary-adrenal axis. We gave mares the opioid antagonist, naloxone (NAL), at either a high (0.5 mg/kg i.v. bolus, followed by infusion of 0.25 mg/kg.h; n = 4) or low (0.2 mg/kg i.v. bolus; n = 6) dose rate. Pituitary venous blood was collected continuously, divided into 0.5- or 1-min segments for 15-30 min before and 1 h after the NAL bolus, and assayed for CRH, arginine vasopressin (AVP), and ACTH. The mares tolerated NAL administrat...
Effects of gonadal steroids on the opioid regulation of LH and prolactin release in ovariectomized pony mares. The aim of the present study was to investigate the role of ovarian steroids in the opioid regulation of LH and prolactin release in mares. Effects of the opioid antagonist naloxone on LH and prolactin secretion were determined in ovariectomized pony mares. The animals were pretreated with either progesterone (500 micrograms kg-1) or oestradiol benzoate (10 micrograms kg-1) for 8 days and subsequently with a combination of progesterone and oestradiol for an additional 8 days. Naloxone administration (0.5 mg kg-1 i.v.) resulted in a significant release of LH as well as prolactin in mares after ...
Complications with the use of carfentanil citrate and xylazine hydrochloride to immobilize domestic horses. Carfentanil citrate, the only opioid approved in the United States for immobilizing large exotic animals, increasingly has been used to chemically restrain exotic horses, such as Prezwalski's horses (Equus przewalskii) and wild horses (E caballus). Because carfentanil's duration of action is long and renarcotization may develop 2 to 24 hours after administration of antagonists, a study was designed to compare the physiologic effects of opioid antagonists, using domestic horses chemically restrained with xylazine hydrochloride and carfentanil. The study was terminated after the initial 3 horses...
Pituitary-adrenal activity and opioid release in ponies during thiopentone/halothane anaesthesia. The effect of thiopentone/halothane anaesthesia on the release of endogenous opioid, adrenocorticotrophin, arginine vasopressin, cortisol and catecholamine was investigated in ponies. The contribution made by halothane itself was studied by maintaining six ponies with a constant 1.2 per cent end tidal halothane concentration and five with a concentration ranging between 0.8 and 1.2 per cent. Cardiorespiratory depression was more prolonged in the ponies receiving a constant 1.2 per cent end tidal halothane concentration than in those which received less halothane. Plasma lactate concentration i...
Involvement of endogenous opioids in the regulation of LH and testosterone release in the male horse. To investigate the involvement of endogenous opioids in the regulation of gonadotrophin release in male horses, effects of the opioid antagonist naloxone (0.5 mg kg-1 i.v.) on plasma LH and testosterone concentrations and the possible influence of season and of gonadal steroids were investigated. To determine quantitative as well as qualitative changes in gonadotrophin release, LH concentrations were measured by radioimmunoassay and by an in vitro bioassay. Experiments were performed in May, August and December. In stallions, basal LH secretion in May and August was significantly higher than i...
Effects of the opioid antagonist naloxone on release of luteinizing hormone in mares during the anovulatory season. To investigate an involvement of endogenous opioids in the regulation of circannual changes in reproductive activity, effects of the opioid antagonist naloxone on the concentration of immunoreactive and bioactive luteinizing hormone (LH) in plasma were measured in mares during the anovulatory season. Naloxone (0.5 mg/kg i.v.) caused a significant increase (P < 0.05) in immunoreactive as well as bioactive LH concentration in plasma. The amplitude of the increase in LH concentrations measured with an in vitro bioassay was more pronounced than the amplitude of the increase in LH secretion dete...
Comparative effects of mu and kappa opiate agonists on the cecocolic motility in the pony. The electrical and mechanical activity of the large intestine and its response to administration of opiate mu and kappa agonists were assessed from electrodes and inductograph coils chronically implanted on the cecocolic segment in six ponies given a diet of hay and concentrates. Before the drugs were given, migrating complexes propagating from the cecum into the colon occurred at the rate of 1.5 to 16/hour. During this propulsive activity, the cecocolic sphincter opened and closed allowing the outflow of cecal contents and preventing the backflow of colic contents. Each pony was used as its o...
Narcotics and local anesthetics. The recognition and alleviation of animal pain is a growing veterinary and public concern. Pain can be of an acute or chronic nature with different behavioral manifestations. Physiologically, pain is a dynamic and complex phenomenon that produces changes in the central and autonomic nervous systems as well as in the endocrine system. Horses and other animals appear to possess an endogenous pain-suppressing system involving the brainstem and spinal cord. This system can modulate pain perception and the responses to it. The recently discovered endogenous opioid peptides (endorphins and enkephali...
Postoperative analgesia using phenylbutazone, flunixin or carprofen in horses. Horses undergoing surgery were randomly assigned to one of three groups to receive phenylbutazone at 4 mg/kg (n = 72), flunixin at 1 mg/kg (n = 68) or carprofen at 0.7 mg/kg (n = 63) by slow intravenous injection at the end of surgery, just before they were disconnected from halothane. Pain was assessed by either of two resident surgical clinicians (who did not know which non-steroidal anti-inflammatory drug had been given) when the horses first stood up, two and four hours later and the next morning. If repeated doses of analgesic drugs were given the time was recorded and taken as an end poi...
Naloxone affects gastrointestinal functions and behaviour in horses. Clinical effects of the opioid antagonist naloxone were investigated in healthy horses. Naloxone caused a transient increase in the frequency of defecations, a softening of the faeces and alterations in the intensity of abdominal borborygmi. Total serum protein concentrations decreased. Behavioural changes like frequent yawning and flehmen occurred, heart rate decreased and respiratory rate tended to increase but no clinical signs of distress or pain were observed. It can be concluded that in healthy animals naloxone had only minor side-effects and could be used to investigate the physiologica...
Inhibition of gonadotrophin release in mares during the luteal phase of the oestrous cycle by endogenous opioids. Effects of the opioid antagonist naloxone on concentrations of LH and FSH in plasma were measured in mares during different stages of the oestrous cycle. During the follicular phase of the cycle, naloxone (300 mg i.v.) had no discernible effects on basal concentrations of LH and FSH. A significant increase in plasma LH (P < 0.01) and FSH (P < 0.05) concentrations was observed after naloxone in mares during the luteal phase. This response was not different between suckled and non-suckled mares. The gonadotrophin-releasing hormone analogue buserelin (0.02 mg i.v.) caused a significant (P < 0.05)...
[Pain prevention and pain treatment in small and large domestic animals]. The aim of this article is to emphasize the need for analgesic medication in animals in possibly painful situations, especially in the postoperative period. The two large groups of compounds used as analgesics--the opiates and the nonsteroidal antiinflammatory drugs (NSAIDs)--are described with special reference to their pharmacokinetics, side-effects and toxicity, their mechanism of action, their indications and contraindications. Recommended doses of the different drugs available are given for the dog, the cat, the horse, the swine and the small and large ruminants.
Secretory patterns and rates of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone revealed by intensive sampling of pituitary venous blood in the luteal phase mare. We used our unique nonsurgical technique for collecting pituitary venous (pit) blood to study GnRH, FSH, and LH secretion patterns in midluteal phase mares. This method does not perturb endocrine function and allows continuous monitoring of GnRH and gonadotropin (Gn) secretion, determination of the amount of GnRH perfusing gonadotropes, and direct measurements of the amounts of Gn secreted. In a total of 80 h of 5-min sampling in four mares, eight Gn peaks occurred; however, more frequent sampling was needed to define secretory events precisely. Therefore, pit blood was collected continuously ...
Diurnal variation in plasma ir-beta-endorphin levels and experimental pain thresholds in the horse. Diurnal variation in nociceptive sensitivity and plasma immunoreactive beta-endorphin (ir-BEND) concentrations was examined in eight healthy Thoroughbred horses. Pain thresholds, ir-BEND concentrations, rectal temperature, heart rate, respiratory rate and pupil diameter were measured over a 24 hour period. Nociceptive sensitivity was determined using two objective measures of pain: the skin-twitch reflex latency and the hoof withdrawal reflex latency. Significant variation in both nociceptive thresholds and ir-BEND concentrations were noted over the 24 hour period, with elevated pain threshold...
N-acetylation and C-terminal proteolysis of beta-endorphin in the anterior lobe of the horse pituitary. beta-Endorphin is post-translationally processed to both N-acetylated and C-terminally shortened derivatives in the anterior lobe of the horse pituitary, a processing pattern qualitatively different from that of the rat and virtually every other mammalian species. Thus, separation of the molecular forms of beta-endorphin using gel filtration and ion exchange chromatography showed that the horse anterior lobe primarily contains beta-endorphin-1-31 and N-acetyl-beta-endorphin-1-27 along with smaller amounts of beta-lipotropin, beta-endorphin-1-27, and N-acetyl-beta-endorphin-1-31 and -1-26, in c...
The pharmacology of local anesthetics. Understanding of the pharmacology of local anesthesia is important for selection of a local anesthetic for use in equine standing surgery. In general, the action potential is inhibited by local anesthetics by preventing the influx of sodium ions across the axonal membrane. The physicochemical properties of each local anesthetic determine the onset of action, potency, and duration of action. Procaine, chlorprocaine, lidocaine, and mepivacaine are the local anesthetics still used clinically in horses; lidocaine is the most widely used. The future of equine local anesthesia may see the introducti...
Chemical restraint for surgery in the standing horse. Chemical restraint can be a useful pharmacologic tool to assist the veterinarian performing surgery in the standing horse. The agents discussed impose minimal adverse side effects and are considered relatively safe when administered in the doses described. Acetylpromazine, the most widely used tranquilizer, produces mild sedation but no analgesia. The use of tranquilizers for surgical procedures requires the combined use of either a local anesthetic technique or a sedative-hypnotic or opiate to provide analgesia. Sedative-hypnotics such as xylazine and detomidine or opiates such as morphine an...
Morphine and etorphine: XIV. Detection by ELISA in equine urine. We have raised antibodies to morphine and etorphine and developed one-step enzyme-linked immunosorbent assays (ELISA) for these drugs as part of a panel of post race tests for drugs in racing horses. These tests are simple, can be completed in 2 h, and can be read by visual inspection. The morphine ELISA has an I50 for morphine of about 1.5 ng/mL, while the etorphine ELISA has an I50 for etorphine of 250 pg/mL. Cross-reactivity studies show that the antimorphine antibody cross-reacts well with levorphanol, hydromorphone, and oxycodone, while the anti-etorphine antibody showed no cross-reactivi...
Effect of low-dose butorphanol on halothane minimum alveolar concentration in ponies. Minimum alveolar concentration (MAC) for halothane was measured before and after administration of intravenous butorphanol (0.022 and 0.044 mg/kg in bodyweight in nine yearling Shetland ponies. Arterial blood pressure, heart rate, respiratory rate, expired CO2 and rectal temperature was also measured. Even though mean MAC values decreased 10 and 9 per cent after the low and high doses respectively, they were not statistically different from those measured prior to butorphanol. Halothane MAC values increased after butorphanol in two ponies, both animals increasing locomotor activity and demonst...
Naloxone-induced abdominal distress in the horse. Endogenous opioid peptides have been implicated in the regulation of pain perception, behaviour, gastrointestinal activity and other physiological responses. However, the functional role of these peptides in the horse has yet to be elucidated. The opioid antagonist, naloxone, is often administered to infer endogenous opioid effects. In the present study, naloxone (0.75 mg/kg bodyweight) was administered to eight Thoroughbred racehorses and a number of behavioural and autonomic responses were measured. Naloxone produced rapid onset diarrhoea, restlessness, abdominal checking, tachycardia, tachy...