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.
Remifentanil in the horse: identification and detection of its major urinary metabolite. Remifentanil (4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic acid methyl ester) is a mu-opioid receptor agonist with considerable abuse potential in racing horses. The identification of its major equine urinary metabolite, 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic+ ++ acid, an ester hydrolysis product of remifentanil is reported. Administration of remifentanil HCl (5 mg, intravenous) produced clear-cut locomotor responses, establishing the clinical efficacy of this dose. ELISA analysis of postadministration urine samples readily detected fentany...
Regulation of seasonal reproductive activity in the stallion, ram and hamster. This review considers seasonal reproduction in male animals with emphasis on the stallion, ram and hamster. The pineal hormone melatonin is the common link between photoperiod and reproduction. An increase in the daily diurnal period of melatonin secretion is associated with a decrease in GnRH release in long-day breeders, but an increase in GnRH release in short-day breeders. Melatonin influences GnRH release within or close to the mediobasal hypothalamus in rams; whereas melatonin receptors have not been found in the hypothalamus of horses. Prolactin release is positively correlated with day...
Opioidergic and dopaminergic effects on LH and prolactin release in pony mares at different times of the year. The effects of dopaminergic and opioidergic systems on LH and prolactin release in Pony mares were investigated. Experiments were performed in intact mares during the non-breeding and the breeding seasons and in ovariectomized mares in November, March and May. Mares were treated with the dopamine D2-antagonist sulpiride, the opioid antagonist naloxone and naloxone plus sulpiride and saline. Naloxone alone and in combination with sulpiride increased plasma LH concentrations in intact anovulatory mares and in cyclic luteal phase mares, whereas sulpiride alone had no effect. None of the treatment...
The role of endogenous opioids in the ovulatory LH surge in mares. Removal of opioid inhibition of GnRH neurones is thought to be a critical event in generating the ovulatory surge in some species. In the present study, a nonsurgical technique was used to collect pituitary venous blood samples from eight mares every 0.5-1.0 min for 1 h before and after administration of the opioid receptor antagonist naloxone (0.2 mg kg(-1), i.v.), to investigate whether opioid inhibition is also important in mares. Jugular blood samples were taken at 10-15 min intervals. Mares were studied 0, 1 or 2 days before ovulation. Naloxone administration increased mean rates of GnRH ...
Methadone screening of racehorses. The misuse of opiates in racehorses relates to their effect of increasing locomotor activity. Because methadone, a narcotic analgesic, has been suspected of use as a doping compound in the past, it was added to the list of banned drugs and should be considered in doping control. Because the literature fails to provide information on detection of methadone in blood or urine of horses, an enzyme-linked immunosorbent assay was developed to monitor this narcotic in equine body fluids. Combined with high-performance liquid chromatography, the immunoassay also served to confirm positives indicated b...
Analgesia. Critical to reducing patient morbidity as well as heightened ethical awareness, alleviation of pain in animals has become integral to medical case management and surgical procedures. Pharmacotherapy is directed at peripheral nociceptors, primary and secondary spinal neurons, and pain-processing areas in the CNS. Accordingly, three primary pharmacologic strategies have evolved: drugs that bind to and activate opioid receptors, drugs that bind to and activate alpha 2 receptors, and drugs that reduce de novo prostaglandin synthesis. In horses, the two predominant types of pain encountered are mus...
Seasonal variation and opioidergic regulation of growth hormone release in cyclic, ovariectomized, and pregnant pony mares. Modulation of reproductive functions is one of the multiple effects of growth hormone (GH). To investigate effects of reproductive functions on GH release in the horse, plasma GH concentrations in ovary-intact (n = 7) and ovariectomized (n = 8) mares during the anovulatory and breeding seasons and in pregnant mares (n = 6) at various stages of gestation were determined. To analyze an opioidergic regulation of GH release, repeated blood samples were taken over 3 h, and mares were injected with the opioid antagonist naloxone (0.5 mg/kg i.v.) or saline. GH was determined by RIA with an antiserum ...
Alpha 2 agonists and antagonists. The alpha 2 agonists can produce reliable dose-dependent sedation and analgesia in most species. Nevertheless, they can also produce significant physiological adverse side effects depending on dose, rate, route of administration, and the concurrent use of other CNS depressants. For this reason, it may be best to use a low dose of an alpha 2 agonist as a preanesthetic agent. The alpha 2 agonists are best suited for young, healthy, exercise-tolerant patients. The combining of low doses of alpha 2, opioid, and benzodiazepine agonists results in a synergistic CNS depressant response while minimizi...
Lack of local anaesthetic efficacy of fentanyl in the abaxial sesamoid block model. Fentanyl and other opioid drugs have their effect in the central nervous system; however, activity at peripheral sites has also been demonstrated. Pain-suppression activity at peripheral sites raises the possibility of skilled individuals producing local anaesthetic effects with small doses of opioid drugs that would be difficult to detect forensically and could be used to affect the outcome of a race. Therefore, the local pain-suppression effect (peripheral nerve inhibition) of fentanyl was tested using an abaxial sesamoid block/hoof withdrawal model. With this model, fentanyl did not produce...
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...
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...