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.
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...
Sandbaumhüter FA, Vimercati S, Thormann W, Mevissen M.The anesthetic ketamine is often combined with analgesics and benzodiazepines in equine medicine. Therefore, drug-drug interactions are possible. Enzyme kinetics for ketamine N-demethylation were determined using equine CYP3A94, CYP3A95 and CYP3A97, and the effect of medetomidine, diazepam and methadone on the ketamine metabolism was studied in vitro. Ketamine was incubated with the CYPs or equine liver microsomes (ELM) alone or in presence of medetomidine, diazepam and/or methadone for different times. Norketamine levels were determined using enantioselective capillary electrophoresis (CE) wi...
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...
Dönselmann Im Sande P, Hopster K, Kästner S.Various opioids are available for use in equine medicine. Studies directly comparing their analgesic effects and side effects are rare. Therefore, the aim of this study was to compare the antinociceptive effect and the duration of analgesia of two different doses of morphine, butorphanol and levomethadone in horses. Methods: Eight adult, healthy horses were used for this randomized, placebo-controlled, blinded cross-over trail. Each horse received placebo (P = 0.9% saline) and morphine (M = 0.1 mg/kg; M = 0.2 mg/kg), butorphanol (B = 0.1 mg/kg; B = 0.2 mg/kg) and levomethadone (L...
Wetmore LA, Pascoe PJ, Shilo-Benjamini Y, Lindsey JC.OBJECTIVE To determine the locomotor response to the administration of fentanyl in horses with and without the G57C polymorphism of the μ-opioid receptor. ANIMALS 20 horses of various breeds and ages (10 horses heterozygous for the G57C polymorphism and 10 age-, breed-, and sex-matched horses that did not have the G57C polymorphism). PROCEDURES The number of steps each horse took was counted over consecutive 2-minute periods for 20 minutes to determine a baseline value. The horse then received a bolus of fentanyl (20 μg/kg, IV), and the number of steps was again counted during consecutive 2-...
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...
Knych HK, Steffey EP, White AM, McKemie DS.Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals. Objective: To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days. Methods: Experimental. Methods: Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasion...
General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contra...
Hunter BG, Parker JE, Wehrman R, Stang B, Cebra CK.To determine synovial concentrations of morphine after intravenous regional limb perfusion (IVRLP) with morphine or morphine in combination with gentamicin in clinically healthy, standing sedated horses. Methods: Experimental. Methods: Adult horses (n = 6). Methods: IVRLP was performed using 0.1 mg/kg morphine (M) in standing sedated horses. After a 3-week washout period, IVRLP was performed on the same forelimb with a combination of 0.1 mg/kg morphine and 1 g gentamicin (M/G). Synovial fluid from the middle carpal joint of the perfused limb and jugular blood samples were collected i...
Taylor PM, Hoare HR, de Vries A, Love EJ, Coumbe KM, White KL, Murrell JC.Buprenorphine, a μ-agonist opioid, has recently been licensed for equine use, but butorphanol, a κ-agonist opioid, is more commonly used in horses. The effect of the 2 opioids has not previously been compared in a large clinical study. Objective: To compare post operative analgesia and physiological variables in horses undergoing elective surgery following premedication with either buprenorphine or butorphanol in a conventional clinical setting. Methods: Multicentre, prospective, randomised, blinded clinical investigation. Methods: Eighty-nine healthy horses admitted for elective surgery to ...
Wang CC, Hartmann-Fischbach P, Krueger TR, Wells TL, Simonson A, Compton JC.Due to opiorphin's analgesic and antidepressant functions, its illicit use is rumored in some racing jurisdictions. Opiorphin is very difficult to detect due to its hydrophilic nature and rapid degradation in plasma and urine samples. METHODOLOGY & RESULTS: We have developed a sensitive, reliable method for opiorphin detection and confirmation in equine samples, using EDTA to inhibit analyte degradation between the time of collection and analysis. Opiorphin was extracted by weak cation exchange followed by analysis using HILIC-MS/MS. The method was validated and the LOD was determined to b...
Hertzsch R, Emmerich IU, Lachenmeier DW, Sproll C, Monakhova YB, Aboling S, Bachmann U, Vervuert I.Opioid alkaloids were identified in the urine of horses during an anti-doping control and in a case of intoxication. In both cases, it was suspected that the horses had ingested poppy-contaminated feed. To verify this suspicion, possible opioid alkaloid sources in Germany were identified through a literature research. Additionally, the contaminated feed was botanically and chemically analysed. The results indicated that both cases were most probably caused by the poppy in the feed. This highlights the previously underestimated risk of an intake of poppy-contaminated feed in horses. Recommendat...
Carregaro AB, Freitas GC, Ribeiro MH, Xavier NV, Dória RG.Continuous-rate infusion (CRI) of drugs results in more stable plasma drug concentrations than administration of intermittent boluses, thus providing greater stability of physiological parameters. The aim of this study was to evaluate the physiologic and analgesic effects of the administration of morphine, butorphanol, tramadol or methadone by CRI in horses with induced synovitis of the radiocarpal joint. Results: Increased values of cardiorespiratory parameters and body temperature were observed in all groups after initiation of opioid administration, and these increases were sustained throug...
Robinson MA, Guan F, McDonnell S, Uboh CE, Soma LR.Dermorphin is a μ-opioid receptor-binding peptide that causes both central and peripheral effects following intravenous administration to rats, dogs, and humans and has been identified in postrace horse samples. Ten horses were intravenously and/or intramuscularly administered dermorphin (9.3 ± 1.0 μg/kg), and plasma concentration vs. time data were evaluated using compartmental and noncompartmental analyses. Data from intravenous administrations fit a 2-compartment model best with distribution and elimination half-lives (harmonic mean ± pseudo SD) of 0.09 ± 0.02 and 0.76 ± 0.22 h, respe...
Rigotti C, De Vries A, Taylor PM.A prospective, randomised, blinded, clinical trial in 47 ponies compared butorphanol and buprenorphine administered intravenously with detomidine prior to castration under anaesthesia. Detomidine 12 μg/kg intravenously was followed by butorphanol 25 μg/kg (BUT) or buprenorphine 5 μg/kg (BUP) before induction of anaesthesia with intravenous ketamine and diazepam. Quality of sedation, induction and recovery from anaesthesia, response to tactile stimulation, and surgical conditions were scored. If anaesthesia was inadequate 'rescue' was given with intravenous ketamine (maximum three dose...
Knych HK, Steffey EP, Casbeer HC, Mitchell MM.Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use. Objective: To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5-13 days and describe selected, associated dose- and time-related behavioural and physiological responses to plasma fentanyl concentration. Methods: Experimental. Methods: Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 μg/kg bwt) at 10-min intervals. Blood samples were collected before and at selected time...
Risberg ÅI, Spadavecchia C, Ranheim B, Hendrickson EH, Lervik A, Haga HA.To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. Methods: Prospective, experimental cross-over trial. Methods: Nine Norwegian Fjord research foals. Methods: Buprenorphine, 10 μg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid m...
Gozalo-Marcilla M, Gasthuys F, Schauvliege S.To review the literature with regard to the use of different intravenous agents as supplements to inhalational anaesthesia in horses. The Part 2 of this review will focus in the use of opioids and α2 -agonists. Methods: Pubmed and Web of Science. Search terms: horse, inhalant anaesthesia, balanced anaesthesia, partial intravenous anaesthesia, opioids, morphine, pethidine, butorphanol, methadone, fentanyl, alfentanil, remifentanil, sufentanil, xylazine, romifidine, detomidine, medetomidine and dexmedetomidine. Conclusions: Different drugs and their combinations can be administered systemically...
Lizarraga I, Castillo-Alcala F.Combinations of α2 -adrenoceptor and opioid agonists are commonly used in equids, but little scientific information is available on donkeys. Objective: To compare the sedative and hypoalgesic effects of xylazine alone or in combination with different dosages of butorphanol in donkeys. Methods: Placebo-controlled, operator-blinded, randomised, crossover, Latin square study. Methods: Six donkeys received intravenous normal saline and normal saline (NS-NS); xylazine (0.5 mg/kg bwt) and normal saline (X-NS); xylazine and 10 μg/kg bwt butorphanol (X-B10); xylazine and 20 μg/kg bwt butorpha...
Sanchez LC, Robertson SA.Currently, approaches to pain control in horses are a mixture of art and science. Recognition of overt pain behaviours, such as rolling, kicking at the abdomen, flank watching, lameness or blepharospasm, may be obvious; subtle signs of pain can include changes in facial expression or head position, location in the stall and response to palpation or human interaction. Nonsteroidal anti-inflammatory drugs (i.e. phenylbutazone, flunixin meglumine and firocoxib), opioids (i.e. butorphanol, morphine and buprenorphine) and α2 -adrenergic agonists (i.e. xylazine, detomidine, romifidine and medetomid...
Gozalo-Marcilla M, Gasthuys F, Schauvliege S.To review the literature with regard to the use of different intravenous agents as supplements to inhalational anaesthesia in horses. These drugs include lidocaine, ketamine, opioids and α2 -agonists. The Part 1 of this review will focus in the use of lidocaine and ketamine. Methods: Pubmed & Web of Science. Search terms: horse, inhalant anaesthesia, balanced anaesthesia, partial intravenous anaesthesia, lidocaine, ketamine. Conclusions: Different drugs and their combinations can be administered systemically in anaesthetized horses, with the aim of reducing the amount of the volatile agen...
Benmansour P, Husulak ML, Bracamonte JL, Beazley SG, Withnall E, Duke-Novakovski T.To examine the cardiopulmonary effects of infusions of remifentanil or morphine, and their influence on recovery of horses anesthetized with isoflurane and dexmedetomidine. Methods: Randomized crossover study with 7-day rest periods. Methods: Six adult horses (507 ± 61 kg). Methods: After the horses were sedated with xylazine, anaesthesia was induced with ketamine and diazepam, and maintained with isoflurane. After approximately 60 minutes, a dexmedetomidine infusion was started (0.25 μg kg(-1) then 1.0 μg(-1) kg(-1) hour(-1) ) in combination with either saline (group S), morphine (0.15 mg ...
Martin-Flores M, Campoy L, Kinsley MA, Mohammed HO, Gleed RD, Cheetham J.To evaluate the hypothesis that epidural morphine (0.1 mg kg(-1) ) decreases pain in horses after laparoscopic surgery without adversely affecting gastrointestinal (GI) motility. Methods: Randomized clinical trial. Methods: Eighteen horses undergoing laparoscopic cryptorchidectomy under general anesthesia. Methods: Horses were randomly assigned to receive either epidural morphine (0.1 mg kg(-1) ) or no epidural before the start of surgery. Pain behaviors were assessed during the first two post-operative days using a numerical rating scale. Barium-filled spheres were administered through a naso...
Knych HK, Steffey EP, McKemie DS.The objective of the current study was to describe the pharmacokinetics of morphine and its metabolites following intravenous administration to the horse. A total of eight horses (two per dose group) received a single intravenous dose of 0.05, 0.1, 0.2, or 0.5 mg/kg morphine. Blood samples were collected up to 72 h postdrug administration, analyzed using LC-MS/MS and pharmacokinetic parameters determined. Behavior, step counts, and gastrointestinal activity were also assessed. The beta and gamma half-life for morphine ranged from 0.675 to 2.09 and 6.70 to 18.1 h, respectively, following admini...
Foreman JH, Ruemmler R.There are no peer reviewed, blinded controlled studies regarding the skeletal analgesic efficacy of intramuscularly administered meperidine in horses. Objective: Using an adjustable heart bar shoe model of equine foot pain, the objective of this study was to test the hypothesis that meperidine (pethidine) administered intramuscularly would prove more efficacious in alleviating lameness than a saline placebo. Methods: Crossover pharmacodynamic experiment. Methods: Eight healthy adult Thoroughbred horses randomly underwent weekly i.m. treatments 1 h after lameness induction: saline placebo (1â...
Steel R, Timms M, Levina V, Vine J.The Dermorphins are a family of peptides that act as potent agonists of the opioid μ receptor. Originally identified as a seven amino acid peptide on the skin of the South American Phyllomedusa frog, peptide chemists have since developed a large number of Dermorphin variants, many with superior opioid activity to the original peptide. Dermorphins are unique among the peptide opioid agonists as they appear to have a limited ability to cross the blood brain barrier, producing effects on both the central and peripheral nervous systems. It is this ability of Dermorphins to provide central anaesth...
Guedes AG, Knych HK, Soares JH, Brosnan RJ.This study evaluated the pharmacokinetics and physiological effects of tramadol during repeated oral administrations in horses. Nine adult healthy horses were administered tramadol at 5 and 10Â mg/kg orally every 12Â h for 5Â days in a randomized, crossover design with a 3-week washout between treatments. Plasma concentrations of tramadol, O- and N-desmethyltramadol (M1 and M2) were measured using Liquid-Chromatography-Mass Spectrometry at predetermined time points following each tramadol administration. Cardiovascular, respiratory and gastrointestinal physiological variables were monitored an...
Lizarraga I, Castillo-Alcala F.Combinations of α2 -adrenoceptor and opioid agonists are commonly used in equids, but little scientific information is available on donkeys. Objective: To compare the sedative and hypoalgesic effects of xylazine alone or in combination with different dosages of butorphanol in donkeys. Methods: Placebo-controlled, operator-blinded, randomised, crossover, Latin square study. Methods: Six donkeys received intravenous normal saline and normal saline (NS-NS); xylazine (0.5 mg/kg bwt) and normal saline (X-NS); xylazine and 10 μg/kg bwt butorphanol (X-B10); xylazine and 20 μg/kg bwt butorpha...
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...
Johnson CB, Taylor PM.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...
Nurnberg HG, Keith SJ, Paxton DM.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...
Casella S, Giannetto C, Giudice E, Marafioti S, Fazio F, Assenza A, Piccione G.Adenosine diphosphate (ADP)-induced platelet aggregation in fed and fasted horses after addition of tramadol hydrochloride was evaluated in vitro. On 10 horses citrated blood samples were collected 2h after feeding (fed animals) and 21 h after feeding (fasted animals). Final concentrations of ADP 1 and 0.5 μM, and tramadol hydrochloride (1, 15, 30, 45 and 60 min after the addition of tramadol) were used to determine the maximum degree and initial velocity of platelet aggregation. Repeated measures multifactor analysis of variance (MANOVA) was used to evaluate the effect of feeding/fasting con...
Briefer Freymond S, Bardou D, Beuret S, Bachmann I, Zuberbühler K, Briefer EF.Although stereotypic behaviors are a common problem in captive animals, why certain individuals are more prone to develop them remains elusive. In horses, individuals show considerable differences in how they perceive and react to external events, suggesting that this may partially account for the emergence of stereotypies in this species. In this study, we focused on crib-biting, the most common stereotypy displayed by horses. We compared how established crib-biters ("CB" = 19) and normal controls ("C" = 18) differed in response to a standard "personality" assessment test battery, i.e., react...
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...
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-...
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...
Roberts MC, Argenzio A.Amitraz, atropine, glycopyrrolate and morphine (but not its derivatives, meperidine [pethidine], oxymorphone and butorphanol) produced similar effects on clinically observed intestinal functions and significantly prolonged intestinal transit, as assessed with polyethylene glycol (PEG). However, their mechanisms of action, particularly on intestinal transport (fluid movement), may differ widely. Loperamide appeared to exert a preferential action on intestinal transport rather than motility, as there was no significant delay in PEG transit. The action of amitraz in perturbing smooth muscle coord...
Guedes AG, Knych HK, Soares JH, Brosnan RJ.This study evaluated the pharmacokinetics and physiological effects of tramadol during repeated oral administrations in horses. Nine adult healthy horses were administered tramadol at 5 and 10Â mg/kg orally every 12Â h for 5Â days in a randomized, crossover design with a 3-week washout between treatments. Plasma concentrations of tramadol, O- and N-desmethyltramadol (M1 and M2) were measured using Liquid-Chromatography-Mass Spectrometry at predetermined time points following each tramadol administration. Cardiovascular, respiratory and gastrointestinal physiological variables were monitored an...
Hemmings A, Parker MO, Hale C, McBride SD.Spontaneous stereotypic behaviours are repetitive, compulsive, topographically invariant response patterns commonly observed in captive or domestic animals, which have been linked to dysfunction of basal ganglia input/output pathways. There is evidence that endogenous opioids play a key regulatory role in basal ganglia direct and indirect pathways, but their precise role, both causally and functionally, in spontaneous stereotypic behaviour is unclear. Here we examined the profile of mu- and delta-opioid receptors (density [Bmax] and affinity [Kd]) of basal ganglia structures in stereotypy (nâ€...
Louro LF, Milner PI, Bardell D.Opioid epidural analgesia has been shown to provide effective analgesia in horses. There is a lack of evidence regarding the effect of opioid epidural analgesia on quality of recovery in horses. Objective: Identify whether opioid epidural analgesia influences quality of recovery in horses undergoing general anaesthesia required for management of hindlimb synovial sepsis. Methods: Single-centre retrospective cross-sectional study. Methods: Data were obtained from the clinical records of horses which had undergone arthroscopic or tenoscopic surgery for management of hindlimb synovial sepsis over...
Skrzypczak H, Reed R, Barletta M, Quandt J, Sakai D.To describe the incidence of postanesthetic signs of colic (PASC) in horses and determine if perianesthetic administration of hydromorphone was associated with an increased risk of PASC. Methods: Retrospective, cohort study. Methods: A total of 409 horses. Methods: Anesthesia and clinical records of horses admitted for various procedures from July 2018 to September 2019 were reviewed. Signs of colic and interventions were recorded up to 48 hours after anesthesia. A binomial logistic regression model was used to evaluate the association between the type of surgery, administration of hydromorpho...
Gretler SR, Finno CJ, Kass PH, Knych HK.In humans, the drug metabolizing enzyme CYP2D6 is highly polymorphic resulting in substantial differences in the metabolism of drugs including anti-arrhythmics, neuroleptics, and opioids. The objective of this study was to phenotype a population of 100 horses from five different breeds and assess differences in the metabolic activity of the equine CYP2D6 homolog using codeine as a probe drug. Administration of a probe drug is a common method used for patient phenotyping in human medicine, whereby the ratio of parent drug to metabolite (metabolic ratio, MR) can be used to compare relative enzym...
Menozzi A, Pozzoli C, Zullian C, Poli E, Serventi P, Bertini S.The effects of preferential µ (morphine), selective µ (fentanyl), selective κ (compound U69593) opioid receptor agonists, and nonselective (naloxone) and selective µ (naloxonazine) antagonists on equine small intestinal motility were evaluated in vitro. Samples of circular muscle from equine jejunum were placed in isolated organ baths and drug-induced modifications of both spontaneous and electrically evoked contractile activity were measured. None of the opioid agonists induced a significant change in spontaneous contractions. Fentanyl and U69593 reduced electrically induced contractions,...
Benmansour P, Husulak ML, Bracamonte JL, Beazley SG, Withnall E, Duke-Novakovski T.To examine the cardiopulmonary effects of infusions of remifentanil or morphine, and their influence on recovery of horses anesthetized with isoflurane and dexmedetomidine. Methods: Randomized crossover study with 7-day rest periods. Methods: Six adult horses (507 ± 61 kg). Methods: After the horses were sedated with xylazine, anaesthesia was induced with ketamine and diazepam, and maintained with isoflurane. After approximately 60 minutes, a dexmedetomidine infusion was started (0.25 μg kg(-1) then 1.0 μg(-1) kg(-1) hour(-1) ) in combination with either saline (group S), morphine (0.15 mg ...
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...
General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contra...
Steel R, Timms M, Levina V, Vine J.The Dermorphins are a family of peptides that act as potent agonists of the opioid μ receptor. Originally identified as a seven amino acid peptide on the skin of the South American Phyllomedusa frog, peptide chemists have since developed a large number of Dermorphin variants, many with superior opioid activity to the original peptide. Dermorphins are unique among the peptide opioid agonists as they appear to have a limited ability to cross the blood brain barrier, producing effects on both the central and peripheral nervous systems. It is this ability of Dermorphins to provide central anaesth...
Flynn H, Cenani A, Brosnan RJ, DiMaio Knych HK, de Araujo Aguiar AJ.To determine the pharmacokinetics and pharmacodynamics of high-concentration formulation of buprenorphine (1.8 mg mL; Simbadol) following subcutaneous (SC) administration in horses. Methods: Prospective, randomized, crossover trial. Methods: A group of six healthy adult horses weighing 521-602 kg. Methods: On three occasions, Simbadol (0.005 mg kg; treatment S5), (0.0025 mg kg; treatment S2.5) or saline (treatment SAL) were administered SC at least 7 days apart in random order. Electrical nociceptive threshold (ENT) measured on the neck region, physiologic variables, locomotor activity, degree...
Linardi RL, Stokes AM, Andrews FM.Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. However, its absorption seems to be impaired by the presence of a transmembrane protein, P-glycoprotein, present in different tissues including the small intestine in other species. This study aims to determine the effect of the P-glycoprotein on methadone flux in the equine intestinal mucosa, as an indicator of in vivo drug absorption. Jejunum tissues from five horses were placed into the Ussing chambers and exposed to methadone solution in the presence or absence of Rhodamine 123 or verapami...
Kamerling SG, Dequick DJ, Weckman TJ, Tobin T.Sensitive methods for measuring the analgesic, physiological and behavioural effects of opioids in the horse have recently been developed. Fentanyl, a prototypic mu-opiate receptor agonist, has been previously shown to produce a syndrome characterized by marked analgesia and locomotor stimulation as well as tachycardia, tachypnoea and behavioural arousal. To determine whether other opiate receptors mediate some of the actions of the narcotic analgesics in the horse, an agent with activity at kappa- and to lesser extent mu-receptors was studied using a vigorous experimental protocol. Like fenta...
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...
Skiöldebrand E, Ley C, Björklund U, Lindahl A, Hansson E.Osteoarthritis is a pain-associated progressive disease and pain mediators, such as opioid receptors, expressed in articular cartilage could represent novel therapeutic targets. Acute and chronic stages of OA indicate different metabolic abilities of the chondrocytes depending on inflammatory state. This study aimed to investigate the response of healthy and osteoarthritic chondrocytes and their expression and release of pain mediators in response to acute inflammation. Interleukin-1 beta (IL-1β) and lipopolysaccharide (LPS) were used to induce an acute inflammatory response in cultured equin...
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...
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...
Costa GL, Tabbì M, Bruschetta G, Spadola F, Leonardi F, Bruno F, Iannelli NM, Licata P, Macrì F, Passino ES, Macrì D, Interlandi C.The study aimed to evaluate the analgesic efficacy of tapentadol in horses, by determining plasma serotonin concentration and adrenocortical response, as biomarkers of pain stress in chronic joint disorders. Thirty-six horses (20 females and 16 males) were divided into three groups of 12 subjects each: group A, osteoarthritis (OA), grade 3-4 lameness; group B, OA, grade 5 lameness; and group C, no OA, no lameness, were enrolled. The orthopedic examination included flexion tests, and radiological and ultrasound examinations. The degree of lameness has been estimated from 0 to 5 according to the...
