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.
Dell'Aquila ME, Albrizio M, Guaricci AC, De Santis T, Maritato F, Tremoleda JL, Colenbrander B, Guerra L, Casavola V, Minoia P.The micro-opioid receptor (MOR) was identified in equine oocytes, cumulus and granulosa cells. By RT-PCR, a 441bp fragment was observed. By immunoblotting, a 65 kDa band was detected in samples of winter anestrous whereas in cells recovered in breeding season, two bands, 65 and 50 kDa, were found. The 65 kDa band was significantly more intense in winter anestrous specimens. In samples recovered in the breeding season, this band significantly decreased with the raise of follicle size and was heavier in compact oocytes and cumulus cells. The protein was localized on the oolemma and within the cy...
Shilo Y, Britzi M, Eytan B, Lifschitz T, Soback S, Steinman A.Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat moderate to moderately severe pain in humans. The present study investigated tramadol administration in horses by intravenous, intramuscular, oral as immediate-release and oral as sustained-release dosage-form routes. Seven horses were used in a four-way crossover study design in which racemic tramadol was administered at 2 mg/kg by each route of administration. Altogether, 23 blood samples were collected between 0 and 2880 min. The concentration of tramadol and its M1 metabolite were ...
Sanchez LC, Robertson SA, Maxwell LK, Zientek K, Cole C.Transdermal fentanyl is used clinically in horses based on pharmacokinetic data and antinociceptive effects documented in other species. Objective: Fentanyl IV administration increases both visceral and somatic nociceptive threshold in conscious horses. Methods: Six clinically normal horses, each fitted with a permanent gastric cannula. Methods: Visceral nociception was evaluated with 2 methods of threshold detection--olorectal distention and duodenal distention. Somatic nociception was assessed by measurement of thermal threshold. Fentanyl was administered as an increasing stepwise infusion f...
Derossi R, Medeiros U, de Almeida RG, Righetto FR, Frazílio FO.The aim of the study was to evaluate and compare the effects of caudal epidural administration of meperidine (MP), lidocaine (LD), and a combination of the two (MPLD) in six mature saddle horses. Horses were randomly assigned to receive three treatments (MP 0.3 mg/kg; LD 0.2 mg/kg; and MPLD: MP 0.3 mg/kg and LD 0.2 mg/kg), with at least 1 week between treatments. Drugs were injected into the epidural space between the first and second coccygeal areas in conscious standing horses. Analgesia, ataxia, sedation, cardiovascular and respiratory effects, and rectal temperature were recorded at differ...
Clark L, Clutton RE, Blissitt KJ, Chase-Topping ME.To investigate the effects of peri-operative morphine on the quality and duration of recovery from halothane anaesthesia in horses. Methods: Prospective randomized study. Methods: Twenty-two client owned horses, ASA category I or II. Methods: Horses undergoing elective surgical procedures were divided into two groups and paired according to procedure, body position during surgery, body mass and breed. Group M+ received morphine by intravenous injection (0.15 mg kg(-1)) before induction of anaesthesia and then by infusion (0.1 mg kg(-1) hour(-1)) during anaesthesia. Group M- received the same a...
Thomasy SM, Moeller BC, Stanley SD.To compare the density and binding characteristics of opioid receptor subtypes in horse, rat, and guinea pig cerebral cortex and cerebellum. Methods: Prospective receptor binding study. Methods: Whole brains were obtained from four neurologically normal adult horses during necropsy. Rat and guinea pig brains were obtained commercially. Methods: The cerebellum and cerebral cortex were dissected from each brain, and tissue homogenates prepared. A radioligand binding technique with the highly selective ligands [(3)H]-DAMGO, [(3)H]-U69593, and [(3)H]-DPDPE was used to identify the mu- (mu), kappa-...
Orsini JA, Moate PJ, Kuersten K, Soma LR, Boston RC.The safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60-67 microg/kg, were investigated in six healthy adult horses. Three transdermal fentanyl patches (Duragesic), each containing 10 mg of fentanyl citrate, were applied to the mid-dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it...
Boscan P, Van Hoogmoed LM, Farver TB, Snyder JR.To evaluate the effects of morphine administration for 6 days on gastrointestinal tract function in healthy adult horses. Methods: 5 horses. Methods: Horses were randomly allocated into 2 groups in a crossover study. Horses in the treatment group received morphine sulfate at a dosage of 0.5 mg/kg, IV, every 12 hours for 6 days. Horses in the control group received saline (0.9% NaCl) solution at a dosage of 10 mL, IV, every 12 hours for 6 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (evaluated by use of barium-filled spheres and radio...
Natalini CC, Polydoro Ada S, Linardi RL.To evaluate the effects of subarachnoidally administered hyperbaric morphine, buprenorphine, and methadone on avoidance threshold to noxious electrical stimulation of the perineal, sacral, lumbar, and thoracic regions in horses. Methods: 6 healthy adult horses. Methods: Horses were assigned to receive subarachnoid administration of hyperbaric morphine (0.01 mg/kg), buprenorphine (0.001 mg/kg), methadone (0.01 mg/kg), or 10% dextrose solution in equal volumes (5 mL). Electrical stimulation was applied every 10 minutes for 60 minutes and every 30 minutes for 120 minutes after subarachnoid inject...
Boscan P, Van Hoogmoed LM, Pypendop BH, Farver TB, Snyder JR.To determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine. Methods: 5 healthy adult horses. Methods: Horses were treated with MNTX (1 mg/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphin...
Thomasy SM, Steffey EP, Mama KR, Solano A, Stanley SD.Fentanyl decreases the minimum alveolar concentration (MAC) of inhaled anaesthetics and has been used clinically to reduce the requirements of other anaesthetic drugs in humans and small animals. We hypothesized that i.v. fentanyl would decrease the MAC of isoflurane in horses in a dose-dependent manner. Methods: Following determination of baseline MAC of isoflurane, fentanyl was administered i.v. to target plasma concentrations of 1, 8 and 16 ng ml(-1). Each horse was randomly assigned two of three target concentrations administered in ascending order. Loading and infusion doses for each hors...
Burford JH, Corley KT.Pruritus following a single administration of 100 microg kg(-1) of preservative-free morphine sulphate given via an extradural catheter was seen in a 580 kg horse. The catheter was placed in the first intercoccygeal space. Focal irritation, represented by both local alopecia over the left gluteal muscles and serum exudation, occurred 4-8 hours after injection. This was attributed to the extradural morphine administration.
Love EJ, Lane JG, Murison PJ.To determine the effect of morphine administration on commonly monitored cardio-respiratory variables and recovery quality in horses undergoing anaesthesia and surgery. Methods: Prospective, randomized clinical study. Methods: Thirty-eight thoroughbred horses, 32 geldings and six mares, 3-13 years old, weighing 411-600 kg. Methods: A standard anaesthetic technique was used. Twenty minutes after induction of anaesthesia horses received 0.1 mg kg(-1) (0.1 m) or 0.2 mg kg(-1) (0.2 m) morphine by intravenous injection. A control group did not receive morphine. Heart rate, respiratory rate (fr), me...
Natalini CC, Linardi RL.To evaluate the effects of epidural administration of hydromorphone on avoidance threshold to noxious electrical stimulation of the perineal, sacral, lumbar, and thoracic regions in horses. Methods: 6 healthy adult horses. Methods: Horses were assigned to receive hydromorphone (0.04 mg/kg) or a control solution (20 mL of sterile water) administered epidurally into in the first intercoccygeal space. Treatments were administered at time intervals of > or = 7 days. Electrical stimulation was applied for 6 hours after epidural injection over the dermatomes of the perineal, sacral, lumbar, and t...
van Hoogmoed LM, Boscan PL.Although potent analgesics, opioids decrease intestinal activity, leading to ileus in many species. N-methylnaltrexone (MNTX), an opioid antagonist which does not cross the blood-brain barrier and antagonises the morphine effect on the intestine, directly stimulates motility and restores function without affecting analgesic properties. While its use has been reported in human subjects, there is no information with regard to its usage in the horse. Objective: To determine whether MNTX has an effect on contractile activity of the equine jejunum and pelvic flexure. Methods: Using circular smooth ...
Collinder E, Nyberg F, Sanderson-Nydahl K, Gottlieb-Vedi M, Lindholm A.The opioid neuropeptide haemorphin-7 was measured, by immunoreactivity, in Standardbred horses during low-speed (7 m/s) and high-speed (10 m/s) endurance exercises, lasting 49-58 and 12-16 min respectively. In parallel, heart rate, muscle temperature and plasma lactate concentrations were measured. The profile of the low-speed exercise showed significantly increased heart rate after 10 min [154 beats per minute (bpm)]. After the exercise, muscle temperature (42.1 degrees C) and plasma lactate (4.8 mmol/l) were significantly increased. The profile of the high-speed exercise was comparatively ch...
Albrizio M, Guaricci AC, Maritato F, Sciorsci RL, Mari G, Calamita G, Lacalandra GM, Aiudi GG, Minoia R, Dell'Aquila ME, Minoia P.The development of fertilizing ability in sperm cells is associated with changes in the plasma membrane. However, to date the exact nature of sequentially activated primary receptors and channels and the signal transduction pathways derived from these remains elusive. We analyzed the expression and localization of the mu-opioid receptor in equine spermatozoa. A transcript corresponding to the third extracellular loop that selectively binds mu agonists was amplified, sequenced and compared with the known sequences in humans, rats and cattle. The amplification product showed a high degree of nuc...
Senior JM, Pinchbeck GL, Dugdale AH, Clegg PD.The records of 496 orthopaedic operations on 428 horses were reviewed to estimate the prevalence of, and identify the risk factors for, the development of colic in horses after surgery. Colic was defined as any recognised sign of abdominal pain that could not be attributed to a concurrent disease. Fourteen of the horses developed colic; eight of them were undiagnosed, three were classified as impactions, one as tympanic colic of the colon, one as incarceration of the small intestine in the epiploic foramen, and one as left dorsal displacement of the colon in the nephrosplenic space. Morphine w...
Thomasy SM, Slovis N, Maxwell LK, Kollias-Baker C.This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum f...
Robertson SA.Several ocular procedures, including examination, removal of corneal foreign bodies, nictitans surgery, eyelid repair, and tumor excision,can be successfully performed in the appropriately restrained and sedated standing horse. Sedation is best achieved with xylazine,with or without the addition of acepromazine. Additional analgesia can be provided with appropriate local anesthetic blocks. Surgical conditions are greatly improved by using an auriculopalpebral and supraorbital block and topical anesthetics. More elaborate standing sedation involving continuous rate infusions of lidocaine or det...
Natalini CC, Robinson EP.Heart rate, arterial blood pressures, respiratory rate, body temperature, and central nervous system excitement were compared before and after epidural administration of morphine (0.1 mg/kg), butorphanol (0.08 mg/kg), alfentanil (0.02 mg/kg), tramadol (1.0 mg/kg), the k-opioid agonist U50488H (0.08 mg/kg), or sterile water using an incomplete Latin square crossover design in five conscious adult horses. Treatments were administered into the first intercoccygeal epidural space. Significant (P <.05) reductions in respiratory rate were detected after epidural administration of morphine, alfent...
Hellyer PW, Bai L, Supon J, Quail C, Wagner AE, Mama KR, Magnusson KR.To test the hypothesis that the distribution, density, and subtype of opioid and alpha (alpha)-2 adrenergic receptors within the central nervous system (CNS) are significantly different between horse and dog. Methods: Prospective experimental study. Methods: Three dogs (3 years of age) and three horses (2-5 years of age). Animals were opioid- and alpha-2 agonist-free at the time of euthanasia. Methods: Brain tissue was obtained at 126 days post-surgery from dogs and 72 days post-surgery from horses. The brains were removed, sectioned coronally into 1-cm slabs, frozen in methylbutane, which was...
Mircica E, Clutton RE, Kyles KW, Blissitt KJ.To identify the incidence of adverse effects caused by morphine 100-170 micro g kg-1 administration during surgery in horses. Methods: Retrospective case record analysis (1996-2000). Methods: Eighty-four healthy (ASA 1 or 2) horses, mean age 5.5 +/- 3.1 (SD) years (2 months to 16 years), mean weight 524 +/- 14 kg (100-950). Methods: Physiological data and evidence of complications were collected from the anaesthetic records of all animals anaesthetized with romifidine, ketamine, diazepam and halothane and undergoing laryngeal surgery or orchiectomy at the Royal (Dick) School of Veterinary Stud...
Pascoe PJ, Taylor PM.To determine whether specific dopamine receptor antagonists block alfentanil-induced locomotor stimulation in horses. Methods: Randomized, prospective, crossover experiment. Methods: Eight adult horses (462-604 kg). Methods: Doses of dopamine-1 (D1) (NNC 01-0756) and dopamine-2 (D2) antagonists (eticlopride) were selected in a pilot study prior to a three part, blinded, cross-over study. In part 1, horses received 7.5 micro g kg-1 eticlopride, 5 micro g kg-1 NNC 01-0756 or an equal volume of saline. In part 2, they received both antagonists and in part 3, acepromazine at 0.05 mg kg-1. Locomoto...
Robertson SA, Andrew SE.To determine if opioid growth factor (OGF, [Met5]enkephalin) and its specific receptor (OGFr) are present in normal cat, dog and horse cornea. Methods: Normal dog, cat and horse. Methods: Corneas were obtained from animals euthanized for reasons unrelated to this project. One cornea from each of three normal cats, dogs and horses was evaluated. The right or left cornea from each animal was chosen randomly. Corneas were harvested and placed in corneal storage media for transport to The M.S. Hershey Medical Center of The Pennsylvania State University where immunocytochemistry techniques were use...
Aurich JE, Kranski S, Parvizi N, Aurich C.This study investigated the regulation of growth hormone (GH) release in stallions and tested the hypothesis that the somatotrophic axis influences testicular function. Basal plasma GH concentrations, effects of an experimental decrease of GH release on testicular function and an opioidergic regulation of GH release were investigated in Shetland stallions (n=6). No seasonal variations in plasma GH concentrations were found over a 12-month period. Treatment with the somatostatin analogue octreotid (100mg twice daily over 10 days) caused a decrease in semen motility from 38.7+/-8.4% progressivel...
Aurich C, Gerlach T, Aurich JE, Hoppen HO, Lange J, Parvizi N.In the non-breeding season, LH release is reduced via dopaminergic systems in the ram. On the other hand, our previous studies demonstrated an opioidergic inhibition of LH release in stallions outside the breeding season. Thus, in the present study we investigated the dopaminergic regulation of LH and prolactin secretion in stallions, considering interactions between dopamine and opioids. To achieve this, stallions (n=8) were treated with the dopamine antagonist sulpiride (0.6 mg/kg), the opioid antagonist naloxone (0.5 mg/kg), sulpiride plus naloxone or saline in December, March and June. Two...
Robinson EP, Natalini CC.Intercoccygeal, or caudal, epidural injection of local anesthetics is a convenient method of producing analgesia and local anesthesia of the tail and perineal structures in conscious standing horses. This technique has been further developed to provide long duration analgesia and anesthesia by placement of catheters into the epidural space of horses. More recently, opioid, alpha-2 adrenergic agonists, ketamine and other analgesic agents have been administered by caudal epidural injection, providing pain relief in both conscious, standing and anesthetized, recumbent horses. This chapter describ...
Bennett RC, Steffey EP.REGIONAL ADMINISTRATION: There is limited, but convincing, evidence that epidural administration of morphine and some other mu-agonist opioids consistently relieves regional pain in horses. In addition, this effect is not accompanied by notable undesirable effects. On the other hand, a clinically important analgesic action has not been demonstrated for similarly administered kappa-agonist opioids. There has been little objective data presented to support the analgesic effectiveness of intra-articularly administered opioids in horses. However, the evidence of local opioid receptors legitimately...
Castro-Cuellar G, Cremer J, Queiroz-Williams P, Knych HK, Leise BS.The objective of this study was to describe the pharmacokinetics of intra-articular (IA) administered buprenorphine in horses with lipopolysaccharide (LPS)-induced synovitis. Radiocarpal synovitis was induced in six healthy adult horses with the IA injection of LPS (0.5 ng/joint) on two occasions in a randomized cross-over design. Treatments (IA buprenorphine (IAB) at 5 μg/kg plus intravenous saline; and intravenous buprenorphine (IVB) at 5 μg/kg plus IA saline) were administered 4 h following LPS injection. Concentrations of buprenorphine were assessed in plasma and synovial fluid (SF) ...
Luna SP, Taylor PM.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...
Aurich C, Daels PF, Ball BA, Aurich JE.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 ...
Gerring EL.The control mechanisms of gastrointestinal motility are complex. Extrinsic neurohormonal effects modulate an intrinsic system, often called the "gut brain," composed of nervous and neuropeptide components. To exert pharmacologic influence on GI motility, use is made of agents that mimic the external control system. Agents that stimulate opioid receptors, block adrenoceptors, block or facilitate acetylcholine action, or antagonize the action of prostaglandins are used to effect changes in GI motility. The major indications for pharmacologic intervention are to increase motility in constipation,...
Chesnel MA, Clutton RE.Previous studies indicated that perioperative morphine improves recovery quality after general anaesthesia in horses. This clinical trial investigated whether this effect was dose-dependant. Twenty-six horses anaesthetised for surgery were block-randomised to receive one of two intraoperative morphine treatments: Treatment M1 consisted of a constant rate infusion (CRI) of morphine at 0.1mg/kg/h, begun after a loading dose (LD) of 0.15 mg/kg. Treatment M2 was a CRI of 0.2mg/kg/h preceded by an LD of 0.3mg/kg. During recovery, times at the first attempt and at achieving sternal recumbency and st...
Dodman NH, Shuster L, Court MH, Dixon R.Crib-biting in horses is a repetitive behavior pattern which may involve the activation of both narcotic receptors and dopamine receptors in the CNS. Crib-biting frequency, determined in 7 nontreated horses under controlled conditions, was usually linear for many hours and ranged from 0.3 to 14.9 bites/min. Intravenous or IM injections of narcotic antagonists decreased these rates to almost zero by about 20 minutes after the injection was given. The duration of the response to a single injection ranged from 20 minutes for naloxone to 4 hours or more for nalmefene and diprenorphine. Effective d...
Pallarols NB, Lamuraglia R, Guglielminetti A, Ortiz de Elguea MF, Carossino M, Funcia JP.Xylazine and remifentanil in constant rate infusion (CRI) could be used for sedation in horses without adverse effects. The objective was to evaluate behavioral and cardiopulmonary effects of an intravenous (IV) infusion of xylazine and remifentanil for sedation in horses. Xylazine (0.8 mg/kg IV) followed after 3 minutes by a CRI of xylazine and remifentanil (0.65 mg/kg/h and 6 μg/kg/h, respectively) was administered in 10 healthy horses for 60 minutes. Sedation, ataxia, and cardiopulmonary, hematological, and blood gases variables were evaluated. Heart rate decreased significantly durin...
Knych HK, Corado CR, McKemie DS, Scholtz E, Sams R.Tramadol is a synthetic opioid used in human medicine, and to a lesser extent in veterinary medicine, for the treatment of both acute and chronic pain. In humans, the analgesic effects are owing to the actions of both the parent compound and an active metabolite (M1). The goal of the current study was to extend current knowledge of the pharmacokinetics of tramadol and M1 following oral administration of three doses of tramadol to horses. A total of nine healthy adult horses received a single oral administration of 3, 6, and 9 mg/kg of tramadol via nasogastric tube. Blood samples were collected...
Eberspächer E, Stanley SD, Rezende M, Steffey EP.To characterize the pharmacokinetics of fentanyl and the tolerance of foals to the drug following a single application of a commercially available transdermal system (TS). Methods: Prospective experimental study. Methods: Six (two male, four female) foals aged 4-8 days, weighing 56-74 kg. Methods: After placement of a jugular sampling catheter, one fentanyl TS (FTS) containing 10.2 mg fentanyl, released at 100 microg hour(-1), was applied for 72 hours. Blood samples were withdrawn over the course of 90 hours for fentanyl plasma analysis. Before and after the study, weight, complete blood count...
Poth MKM, McKemie DS, Traynham M, Kass PH, Knych HK.The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6-glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a...
Weld JM, Kamerling SG, Combie JD, Nugent TE, Woods WE, Oeltgen P, Tobin T.The effects of naloxone on the cardiovascular, hematologic and metabolic derangements associated with endotoxic and hemorrhagic shock were studied in unanesthetized horses. In the first of 3 experiments blood glucose and lactate levels, hematocrit, white, red and differential white cell counts, rectal temperature and clinical signs were obtained before and after endotoxin (10 micrograms/Kg) administration in 5 horses. In the second experiment, two groups of 3 horses received either intravenous naloxone (0.04 mg/Kg) or saline, 7 minutes prior to endotoxin. In a third experiment two groups of 4 ...
Merritt AM, Campbell-Thompson ML, Lowrey S.Six healthy six to eight-month-old horses were surgically prepared with Ag bipolar electrodes sutured to the gastric antrum and duodenum. Leads from the electrodes were exteriorised through a stab incision in the flank. During experimental sessions the horses were lightly restrained in stocks and electrode leads were connected to a physiograph to record antroduodenal myoelectrical activity. Intravenous (i.v.) injection of 0.05 mg/kg bodyweight (bwt) of the opioid agonist/antagonist, butorphanol was followed within 2 to 3 mins by a normal appearing period of repetitive spike activity, or phase ...
Guan F, Uboh CE, Soma LR, Robinson M, Maylin GA, Li X.Dermorphin is a unique opioid peptide that is 30-40 times more potent than morphine. It was misused and went undetected in horse racing until 2011 when intelligence obtained from a few North American race tracks suggested its use. To prevent such misuse, a reliable analytical method became necessary for detection and identification of dermorphin in post-race horse samples. This paper describes the first liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for such a purpose. Equine plasma and urine samples were pre-treated with ethylenediamine tetra-acetic acid and urea prior to so...
Rowland AL, Glass KG, Grady ST, Cummings KJ, Hinrichs K, Watts AE.To determine the influence of epidural detomidine and morphine on serum corticosteroid concentrations and pain-related behavioral responses in mares during and after ovariectomy via colpotomy. Methods: Blinded prospective study. Methods: Nine university-owned mares. Methods: Five of 9 horses received caudal epidural detomidine hydrochloride (0.01 mg/kg) and morphine sulfate (0.1 mg/kg) prior to surgery. All horses received local anesthetic around the ovarian pedicle, 0.02 mg/kg butorphanol IV at the start of the procedure and after first ovary removal, were sedated as required throughout the p...
Weckman TJ, Tai CL, Woods WE, Tai HH, Blake JW, Tobin T.Pharmacologic effects of alpha-methylfentanyl and 3-methylfentanyl, analogs of fentanyl, were investigated in mares. The ability of an 125I-labeled fentanyl radioimmunoassay (125I-RIA) to detect these methylated fentanyl analogs in individual and pooled urine samples from horses was evaluated. Also, the ability of 7 fentanyl antibodies to react with fentanyl and fentanyl derivatives (sufentanil, alfentanil, and carfentanil) was investigated. Mares were studied in a locomotor test to determine the amount of stimulation methylated fentanyl analogs might induce. Two mares each were given alpha-me...
Hamamoto-Hardman BD, Steffey EP, McKemie DS, Kass PH, Knych HK.Meperidine is a synthetic opioid that belongs to the phenylpiperidine class and is a weak mu receptor agonist. In horses there are a limited number of published studies describing the analgesic effects of systemically administered meperidine in horses. The objective of this study was to describe the pharmacokinetics, behavioral and physiologic effects and effect on thermal threshold of three doses of intravenously administered meperidine to horses. Eight University owned horses (four mares and four geldings, aged 3-8 years were studied using a randomized balanced 4-way cross-over design. Hors...
Roger T, Bardon T, Ruckebusch Y.The electrical and mechanical activity of the digestive tract and its response to the administration of opiate agonists and antagonists was assessed from electrodes and strain gauges chronically implanted on the jejunum and the cecocolonic segments in 3 ponies given a diet of hay and concentrates. Before the drugs were given, 10 to 17 migrating myoelectric complexes/day were recorded on the small intestine, and a rhythmic motor activity (base line) was observed on the proximal portion of the colon at the rate of 3.5 to 6.6/hour. Propagated contractions from the proximal to the distal portion o...
Madry MM, Spycher BS, Kupper J, Fuerst A, Baumgartner MR, Kraemer T, Naegeli H.Compared to blood or urine, drugs can be detected for much longer periods in the long hair of horses. The aim of this study was to establish and validate a highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the detection and quantification of frequently prescribed opioids, sedatives and non-steroidal anti-inflammatory agents in the mane and tail hair of horses. Based on an average growth rate of about 2 cm per month, times of administration reported by horse owners or veterinary physicians were related to drug localizations in hair. Hair samples were collecte...
Gozalo-Marcilla M, Moreira da Silva R, Pacca Loureiro Luna S, Rodrigues de Oliveira A, Werneck Fonseca M, Peporine Lopes N, Taylor PM, Pelligand L.The alpha(α) -agonist detomidine is used for equine sedation with opioids such as methadone. We retrieved the data from two randomized, crossover studies where detomidine and methadone were given intravenously alone or combined as boli (STUDY 1) (Gozalo-Marcilla et al., 2017, Veterinary Anaesthesia and Analgesia, 2017, 44, 1116) or as 2-hr constant rate infusions (STUDY 2) (Gozalo-Marcilla et al., 2019, Equine Veterinary Journal, 51, 530). Plasma drug concentrations were measured with a validated tandem Mass Spectrometry assay. We used nonlinear mixed effect modelling and took pharmacokinetic...
Martins FC, Keating SC, Clark-Price SC, Schaeffer DJ, Lascola KM, DiMaio Knych H.To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses. Methods: Prospective, randomized, crossover study. Methods: A group of six adult healthy horses weighing 585.2 ± 58.7 kg. Methods: Each horse was administered IV hydromorphone (0.025 mg kg; treatment H0.025), hydromorphone (0.05 mg kg; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was tota...
Trim CM, Adams JG, Cowgill LM, Ward SL.The purpose of this survey was to identify complications occurring in horses with colic during anaesthesia and recovery from anaesthesia; and to determine any relationships between these complications and drugs used for induction or maintenance of anaesthesia. Two hundred and thirty nine horses were anaesthetised on a total of 250 occasions for colic surgery between January 1985 and May 1987. Of these, 189 recovered from 200 anaesthetic episodes. Most horses received xylazine and guaifenesin with either thiobarbiturate (68 per cent) or ketamine (24 per cent) and anaesthesia was maintained with...
Roger T, Bardon T, Ruckebusch Y.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...
Aurich C, Gerlach T, Aurich JE, Hoppen HO, Lange J, Parvizi N.In the non-breeding season, LH release is reduced via dopaminergic systems in the ram. On the other hand, our previous studies demonstrated an opioidergic inhibition of LH release in stallions outside the breeding season. Thus, in the present study we investigated the dopaminergic regulation of LH and prolactin secretion in stallions, considering interactions between dopamine and opioids. To achieve this, stallions (n=8) were treated with the dopamine antagonist sulpiride (0.6 mg/kg), the opioid antagonist naloxone (0.5 mg/kg), sulpiride plus naloxone or saline in December, March and June. Two...
This work proposes an application of a minimal complexity physiologically based pharmacokinetic model to predict tramadol concentration vs time profiles in horses. Tramadol is an opioid analgesic also used for veterinary treatments. Researchers and medical doctors can profit from the application of mathematical models as supporting tools to optimize the pharmacological treatment of animal species. The proposed model is based on physiology but adopts the minimal compartmental architecture necessary to describe the experimental data. The model features a system of ordinary differential equations...
Webster A, Pezzanite L, Hendrickson D, Griffenhagen G.Equine practitioners frequently inject local anaesthetics (LA) intra-articularly in both diagnosis of lameness and for pain management intra- or post-operatively with synovial endoscopy. Recent reviews of the human and veterinary literature support the concept that chondrotoxicity of LA on joint tissues depends on the type of drug, dose administered, and duration of exposure. The purpose of this review is to summarise the current literature describing intra-articular local anaesthetic use, including both in vitro and in vivo studies, and to draw some comparisons to literature from other specie...
Júnior GS, de Souza JV, de Souza Ferreira W, Florentino VRD, Valente TC, Comassetto F, Oleskovicz N.This study aimed to evaluate the sedation degree, cardiopulmonary effects, and detomidine-sparing during dental occlusal adjustment in standing horses using a bolus and constant rate infusion (CRI) of detomidine alone or in combination with butorphanol or methadone. In this randomized, blinded clinical trial, 24 healthy adult horses were assigned to the detomidine (DT), detomidine-butorphanol (DB), or detomidine-methadone (DM) group. DT received an intravenous bolus of detomidine (20 μg/kg), followed by CRI at 20 μg/kg/h. DB received detomidine (10 μg/kg) and butorphanol (0.02 mg/kg) boluse...
Alexander F.The effect of morphine, Tinct. opii, loperamide, pethidine and atropine on intestinal transit and the faecal and urinary excretion of water and electrolytes was studied in ponies. The rate of passage of a particulate marker was slowed by morphine, hastened then slowed by loperamide and Tinct. opii, and hastened by atropine. The liquid marker was slowed by Tinct. opii and hastened then slowed by the other drugs. Only loperamide decreased the faecal sodium excretion. This drug also decreased faecal water and weight; it appeared worthy of clinical trial in diarrhoea. Tinct. opii decreased by morp...
Keen B, Cawley A, Fouracre C, Pyke J, Fu S.The emergence of novel doping agents is a continuous issue for analysts who aim to maintain the integrity of horseracing together with the well-being and safety of the animals and riders involved. Untargeted mass spectrometric analysis presents a potential improvement for antidoping as it enables the detection of compounds being indirectly affected by an administered drug. In this study, liquid chromatography-high-resolution mass spectrometry was used to investigate a 12-horse administration study of the synthetic opioid, butorphanol. A mass spectrometric workflow capable of detecting metaboli...
