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PubMed1999

Effect of elevated temperature and light on the stability of butorphanol tartrate.

The purpose of this investigation was to determine the short-term stability of butorphanol tartrate in presence of diluents. A 10-mg/mL solution of butorphanol tartrate was diluted to 5 mg/mL using normal saline, 5% dextrose in water (D5W), or sterile water for injection. The diluted solutions were divided into two groups. The effect of temperature was tested by placing one group of sealed amber vials at room temperature and at 37 degrees C. The effect of light was studied by placing a second group in amber and clear vials, then exposing them directly to light. At regular time intervals over a period of 5 weeks, the solutions were analyzed for butorphanol tartrate and degradation products using a high-performance liquid chromatography assay. The concentration of butorphanol tartrate remained practically unchanged, indicating that butorphanol tartrate is not affected by heat or light in the presence of any of the diluents over a period of 5 weeks.

Butorphanol↗

PubMed1992

Pharmacokinetics and milk residues of butorphanol in dairy cows after single intravenous administration.

The pharmacokinetics of butorphanol tartrate were investigated following intravenous administration of 0.25 mg/kg of body weight to six healthy non-lactating Jersey cows. Three lactating Holstein cows also received 0.045 mg of butorphanol/kg of body weight intravenously to determine the extent and duration of drug transfer into milk. A radioimmunoassay technique was used to measure butorphanol concentrations in plasma and milk. The disposition of butorphanol following intravenous administration was characterized by rapid and extensive distribution followed by a slower elimination phase. Apparent volume of distribution was 4.178 +/- 1.145 (mean +/- SD) 1/kg, mean elimination half-life was 82 min, and clearance was 34.6 +/- 7.7 ml/min/kg. Trace quantities of butorphanol were detected in the cow's milk for up to 36 h following administration. These pharmacokinetic data were compared with pharmacokinetic and pharmacodynamic data for butorphanol in other species and for three other potent opioids in related ruminant species.

Animals↗

PubMed2004

The cardiovascular dose-response effects of isoflurane alone and combined with butorphanol in the green iguana (Iguana iguana).

OBJECTIVE: To assess the cardiovascular effects (arterial blood pressure, heart rate, and metabolic acid-base status) of three doses (MAC multiples) of isoflurane alone and combined with butorphanol in the green iguana (Iguana iguana). STUDY DESIGN: Prospective randomized double-blind, two-period cross-over trial. ANIMALS: Six mature healthy green iguanas (Iguana iguana). METHODS: The iguanas received each of two treatments, saline 0.1 mL kg(-1) (SAL) and butorphanol 1.0 mg kg(-1) (BUT) during isoflurane anesthesia. Treatments were separated by at least 1 week. The iguanas were exposed to each of the three minimum alveolar concentration (MAC) multiples (1.0, 1.5, and 2.0) in random order. Anesthesia was induced with isoflurane and maintained using controlled ventilation. Instrumentation included use of an ECG, airway gas monitor, cloacal thermometer, esophageal pulse oximeter, and the placement of a femoral arterial catheter. Body temperature was stabilized and maintained at 32 degrees C. The treatment was administered, and the animals were equilibrated for 20 minutes at each MAC multiple. At each concentration, the heart rate, blood pressure (systolic, mean, diastolic), end-tidal CO2, and SpO2 were measured. At 1.0 and 2.0 MAC, simultaneous blood samples were drawn from the tail vein/artery complex and femoral catheter for blood gas analysis. Data were analyzed using a two-way analysis of variance for repeated measures looking for differences between treatments and among MAC multiples. RESULTS: There were no significant differences in any of the cardiovascular variables between the treatments. Significant differences among isoflurane MAC multiples were observed for HR, mean, diastolic, and systolic blood pressures. Blood pressure and heart rate decreased with an increasing dose of anesthetic. There were no significant differences between treatments or MAC multiples for any of the blood gas variables. The blood pH, PCO2, HCO3-, and hemoglobin saturation differed significantly between sites. Pulse oximetry values measured from the carotid complex did not correlate with and were significantly different from the calculated hemoglobin saturation values determined using the gas analyzer. CONCLUSION AND CLINICAL RELEVANCE: Cardiovascular depression associated with isoflurane anesthesia in the green iguana is dose dependent. The degree of cardiovascular depression was not significantly different when isoflurane was combined with butorphanol. This finding suggests that the pre-emptive or intraoperative use of butorphanol is unlikely to be detrimental to cardiovascular function. Butorphanol may be a useful anesthetic adjunct to isoflurane anesthesia in the green iguana.

Analgesics, Opioid↗

PubMedDate not supplied

The cardiovascular response of sheep to tiletamine-zolazepam and butorphanol tartrate anesthesia.

Butorphanol tartrate (0.5 mg/kg intravenously [IV]) was administered to six ewes (group 1), 10 minutes before administration of tiletamine-zolazepam (12 mg/kg IV). In six ewes (group 2), butorphanol tartrate and tiletamine-zolazepam were administered simultaneously. Time of administration of butorphanol did not alter hemodynamics or duration of anesthesia significantly. Anesthesia was adequate for 25 to 45 minutes (mean, 31 min) in group 1. The sheep in group 2 were anesthetized effectively for 25 to 50 minutes (mean, 39 min). Neither dosing regimen caused significant changes in right atrial pressure, heart rate, pulmonary vascular resistance, or pulmonary capillary wedge pressure. Mean arterial blood pressure (MABP) decreased an average of 18% from baseline values of 113 mm Hg to a minimum of 84 mm Hg at minute 60 in group 1, and from 111 mm Hg to 92 mm Hg at minute 75 in group 2. The decrease was significant only for group 1. Cardiac output (CO) was significantly decreased 24% from 6.6 L/min at minute 45 in group 1, and 32% from 6.3 L/min at minute 15 in group 2. Systemic vascular resistance (SVR) was increased significantly at minute 15, 11% in group 1 and 37% in group 2. Mild respiratory acidosis was measured by significant decreases in arterial pO2 and pH and a significant increase in pCO2 without significant changes in HCO3-. Results of this study show that (1) tiletamine-zolazepam and butorphanol tartrate produce adequate anesthesia for 25 to 50 minutes; (2) the cardiovascular and anesthetic effects of the dosing schedules were similar; and (3) tiletamine-zolazepam and butorphanol result in decreased CO and MABP with a concomitant increase in SVR, and mild respiratory acidosis.

Anesthesia, Intravenous↗

PubMedDate not supplied

Butorphanol tartrate for partial reversal of oxymorphone-induced postoperative respiratory depression in the dog.

A randomized, blinded, crossover study was designed to evaluate the respiratory, cardiovascular, and behavioral effects of butorphanol given postoperatively to oxymorphone-premedicated and surgically stimulated dogs. Nine healthy adult dogs were premedicated intramuscularly with atropine (0.04 mg/kg), acepromazine (0.10 mg/kg), and oxymorphone (0.2 mg/kg). Anesthesia was induced with thiamylal (12 mg/kg) and maintained with halothane in oxygen. According to the protocol of a concurrent study, all dogs had percutaneous endoscopic gastrostomy (PEG) feeding tubes placed during the first anesthetic episode and removed during the second anesthetic episode. All dogs received postoperatively either butorphanol tartrate (0.2 mg/kg) or an isovolumetric dose of saline placebo, both given intravenously. Respiratory rate (RR), tidal volume (TV), minute ventilation (MV), end-tidal CO2 concentration (ETCO2), heart rate (HR), and indirect diastolic (DP), systolic (SP) and mean arterial (MAP) blood pressures were measured at times 0, 2, 5, 10, 20, 40, 80, and 120 minutes after injection. The time from injection of the test drug until extubation was recorded. RR, MV, HR, and DP were significantly (P < .05) increased, while ETCO2 was significantly decreased, for a minimum of 30 minutes in butorphanol-treated dogs compared with saline controls. TV, SP, and MAP were transiently (< or = 15 minutes) increased in butorphanol-treated dogs compared with saline controls. There was no significant difference between the times to extubation in the butorphanol-treated dogs versus the saline control dogs.

Anesthesia, Inhalation↗

PubMedDate not supplied

Butorphanol does not reduce the minimum alveolar concentration of halothane in dogs.

This study evaluated the effect of butorphanol tartrate, a synthetic opioid agonist-antagonist, on halothane minimum alveolar concentration (MAC) in dogs. Baseline halothane MAC was determined in each of six dogs. Butorphanol was administered and halothane MAC was redetermined. Each dog received butorphanol at 0.2, 0.4, and 0.8 mg/kg intravenously at 1 week intervals. Heart rate and arterial blood pressure decreased after butorphanol administration, but returned to baseline by 50 minutes. There was little effect on respiratory parameters. A halothane-sparing effect was not noted with any butorphanol dose.

Anesthesia, Inhalation↗

PubMed1989

Comparison of detomidine, butorphanol, flunixin meglumine and xylazine in clinical cases of equine colic.

Detomidine hydrochloride, butorphanol tartrate, flunixin meglumine and xylazine hydrochloride were evaluated in a blind multi-centre clinical trial in 152 horses with abdominal pain. The drugs were administered as follows: detomidine 20 or 40 micrograms/kg bodyweight (bwt); butorphanol 0.1 mg/kg bwt; flunixin meglumine 1.0 mg/kg bwt; xylazine hydrochloride 0.5 mg/kg bwt. Each centre compared responses to the two doses of detomidine with those to one of the other analgesics. The drugs were administered intravenously (i.v.) after clinical assessment of the degree of sweating, kicking, pawing, head and body movement, attitude, lip curling, stretching to urinate, pulse rate, respiratory rate and rectal temperature. Similar assessments were repeated at 15 min intervals for at least 1 h. The investigators ranked the response to treatment from 'not satisfactory' to 'highly satisfactory'. Significant differences in sweating, kicking, pawing, head and body movement, attitude, pulse rate and respiratory rate were noted between the horses receiving butorphanol and either dose of detomidine. The investigators' subjective evaluation of the analgesic and sedative effects of either dose of detomidine were significantly better than for butorphanol. Analgesia was rated as highly satisfactory or satisfactory in 93.3 per cent and 6.7 per cent of the horses receiving 40 micrograms/kg bwt of detomidine, 73.3 per cent and 26.7 per cent of the horses receiving 20 micrograms/kg bwt of detomidine, and none of the horses receiving butorphanol. There were no differences in the incidence of side effects with the two compounds. Significant differences were noted in kicking, pawing, head and body movement and attitude between the horses receiving flunixin meglumine and either dose of detomidine. Flunixin meglumine provided significantly less analgesia than either dose of detomidine. Analgesia was rated as highly satisfactory or satisfactory in 73.7 per cent and 21.0 per cent of the horses receiving 40 micrograms/kg bwt of detomidine, 42.9 per cent and 21.4 per cent of the horses receiving 20 micrograms/kg bwt of detomidine, and 6.3 per cent and 37.5 per cent of the horses receiving xylazine. Sedation was considered to be at least satisfactory in 84.2 per cent of the horses receiving 40 micrograms/kg of detomidine, 71.5 per cent of the horses receiving 20 micrograms/kg of detomidine and 53.3 per cent of the horses receiving xylazine.

Adrenergic alpha-Agonists↗

PubMed1997

Effect of acepromazine and butorphanol on halothane minimum alveolar concentration in ponies.

The effect of i.v. acepromazine (0.05 mg/kg bwt), butorphanol (0.05 mg/kg bwt) and a combination of acepromazine and butorphanol on halothane minimum alveolar concentration (MAC) was determined in 7 mixed-breed ponies. Ventilation was controlled, and blood pressure and temperature were maintained within normal limits. Following the determination of baseline MAC, treatments were administered to each pony in a random manner. The control treatment was normal saline. The baseline halothane dMAC for the control group was 0.91 +/- 0.04%, and no significant change occurred after saline administration. Acepromazine decreased (P = 0.0001) the halothane MAC from mean +/- s.e. 0.92 +/- 0.02% to 0.58 +/- 0.04%, and the combination of acepromazine and butorphanol, decreased (P = 0.003) halothane MAC, from mean +/- s.e. 0.95 +/- 0.04% to 0.59 +/- 0.06%. This represents a decrease of 36.9 and 37.8%, respectively. However, the difference between these 2 treatments was not significant. Butorphanol did not significantly change the mean group value for MAC; nevertheless, 3 ponies had an increase, one a decrease, while the MAC did not change in the remaining 3 ponies following butorphanol treatment.

Acepromazine↗

PubMed2004

Pain during injection of propofol: the effect of prior administration of butorphanol.

Propofol causes pain or discomfort on injection in 28%-90% of patients. A number of techniques have been tried for minimizing propofol-induced pain with variable results. We compared the efficacy of butorphanol and lidocaine for prevention of propofol-induced pain. One-hundred-fifty ASA I-II adults, undergoing elective surgery were randomly assigned into 3 groups of 50 each. Group I (NS) received normal saline, Group II (L) received lidocaine 2% (40 mg), and Group III (B) received butorphanol 2 mg. All patients received pretreatment solutions made in 2 mL with normal saline administered over 5 s. One min after pretreatment patients received one-fourth of the total calculated dose of propofol (2.5 mg/kg) over 5 s. Assessment of pain with IV propofol was done by using a four-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain and 3 = severe pain at the time of propofol injection. In the control Group 39 (78%) patients had pain during propofol injection as compared to 21 (42%) and 10 (20%) in the lidocaine and butorphanol groups, respectively (P < 0.05). Butorphanol was the most effective. We therefore suggest the IV pretreatment with butorphanol 2 mg for attenuation of pain associated with propofol injection.

Adult↗

PubMed2001

Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery.

OBJECTIVE: To compare the safety and efficacy of preoperative administration of meloxicam with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery. ANIMALS: 36 dogs undergoing laparotomy, splenectomy, or cystotomy. PROCEDURE: Dogs were randomly assigned to 1 of 3 groups. In the first part of the study, dogs were given a single dose of meloxicam, ketoprofen, or a placebo, and buccal mucosal bleeding times were measured. In the second part of the study, dogs were given meloxicam, ketoprofen, or butorphanol prior to surgery. Dogs in the butorphanol group received a second dose immediately after surgery. Pain scores (1 to 10) were assigned hourly for 20 hours after surgery and used to determine an overall efficacy score for each dog. Dogs with a pain score > or =3 were given oxymorphone for pain. Dogs were euthanatized 8 days after surgery, and gross and histologic examinations of the liver, kidneys, and gastrointestinal tract were conducted. RESULTS: Overall efficacy was rated as good or excellent in 9 of the 12 dogs that received meloxicam, compared with 9 of the 12 dogs that received ketoprofen and only 1 of the 12 dogs that received butorphanol. No clinically important hematologic, biochemical, or pathologic abnormalities were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that preoperative administration of meloxicam is a safe and effective method of controlling postoperative pain for 20 hours in dogs undergoing abdominal surgery; the analgesic effects of meloxicam were comparable to those of ketoprofen and superior to those of butorphanol.

Analgesics, Non-Narcotic↗

PubMed2004

Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol in dogs.

OBJECTIVE: To compare sedative, analgesic, and cardiopulmonary effects after IV administration of medetomidine (20 microg/kg), medetomidine-hydromorphone (20 microg of medetomidine/kg and 0.1 mg of hydromorphone/kg), and medetomidine-butorphanol (20 microg of medetomidine/kg and 0.2 mg of butorphanol tartrate/kg) in dogs. ANIMALS: 6 dogs healthy mixed-breed dogs. PROCEDURE: Instruments were surgically inserted, and heart rate (HR), respiratory rate (RR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), core body temperature, and cardiac output (CO) were measured 0, 5, 10, 15, 30, 45, and 60 minutes after injection. Cardiac index (CI), stroke volume (SV), stroke index (SI), systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated. Arterial samples for blood gas analysis were collected 0, 15, and 45 minutes after injection. Intensity of analgesia, degree of sedation, and degree of muscle relaxation were evaluated at aforementioned time points and 75, 90, 120, 150, 180, and 210 minutes after injection. RESULTS: Administration of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol was associated with increases in SAP, MAP, DAP, MPAP, PCWP, CVP, SVR, PVR, core body temperature, and PaCO2 and decreases in HR, CO, CI, SV, SI, RR, pH, and PaO2. Clinically important differences were not detected among treatments. Medetomidine-hydromorphone and medetomidine-butorphanol provided a longer duration of sedation and better quality of analgesia, compared with medetomidine alone. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine-hydromorphone or medetomidine-butorphanol is associated with improved analgesia and sedation but has cardiopulmonary effects comparable to those for medetomidine alone.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2000

Sedative and cardiorespiratory effects of medetomidine, medetomidine-butorphanol, and medetomidine-ketamine in dogs.

OBJECTIVE: To determine sedative and cardiorespiratory effects of i.m. administration of medetomidine alone and in combination with butorphanol or ketamine in dogs. DESIGN: Randomized, crossover study. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs were given medetomidine alone (30 micrograms/kg [13.6 micrograms/lb] of body weight, i.m.), a combination of medetomidine (30 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg [0.09 mg/lb], i.m.), or a combination of medetomidine (30 micrograms/kg, i.m.) and ketamine (3 mg/kg [1.36 mg/lb], i.m.). Treatments were administered in random order with a minimum of 1 week between treatments. Glycopyrrolate was given at the same time. Atipamezole (150 micrograms/kg [68 micrograms/lb], i.m.) was given 40 minutes after administration of medetomidine. RESULTS: All but 1 dog (given medetomidine alone) assumed lateral recumbency within 6 minutes after drug administration. Endotracheal intubation was significantly more difficult when dogs were given medetomidine alone than when given medetomidine and butorphanol. At all evaluation times, percentages of dogs with positive responses to tail clamping or to needle pricks in the cervical region, shoulder region, abdominal region, or hindquarters were not significantly different among drug treatments. The Paco2 was significantly higher and the arterial pH and Pao2 were significantly lower when dogs were given medetomidine and butorphanol or medetomidine and ketamine than when they were given medetomidine alone. Recovery quality following atipamezole administration was unsatisfactory in 1 dog when given medetomidine and ketamine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a combination of medetomidine with butorphanol or ketamine resulted in more reliable and uniform sedation in dogs than did medetomidine alone.

Adjuvants, Anesthesia↗

PubMed2002

Comparison of transdermal administration of fentanyl versus intramuscular administration of butorphanol for analgesia after onychectomy in cats.

OBJECTIVE: To compare postoperative discomfort assessed by subjective pain score and plasma cortisol concentrations in cats undergoing onychectomy that received analgesia by use of transdermal fentanyl (TDF) patches or an i.m. injection of butorphanol. DESIGN: Randomized prospective clinical trial. ANIMALS: 22 client-owned cats weighing 2.2 to 5 kg (4.84 to 11 lb) undergoing onychectomy. PROCEDURE: Researchers were blinded to which cats received a TDF patch (25 microg/h) 18 to 24 hours prior to surgery or an i.m. injection of butorphanol (0.2 mg/kg (0.09 mg/lb]) at the time of sedation, immediately following extubation, and at 4-hour intervals thereafter for 12 hours. Clinical variables, plasma cortisol concentration, and pain scores were evaluated and recorded 24 hours prior to surgery, at extubation, and 2, 4, 8, 12, 24, 36, and 48 hours after surgery. RESULTS: The TDF group had a lower pain score than the butorphanol group only at 8 hours after surgery. Both groups had significantly lower mean plasma cortisol concentrations 0, 24, 36, and 48 hours after surgery, compared with mean plasma cortisol concentrations prior to surgery. No significant differences in appetite or response to handling the feet were observed between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Our data did not reveal a difference in pain relief between administration of TDF and butorphanol. Plasma cortisol concentrations were not different between groups. Fentanyl appeared to provide equivalent analgesia to butorphanol in cats undergoing onychectomy. The primary advantage of using a TDF patch is that repeated injections are not required.

Administration, Cutaneous↗

PubMed2003

Evaluation of the sedative and cardiorespiratory effects of dexmedetomidine, dexmedetomidine-butorphanol, and dexmedetomidine-ketamine in cats.

OBJECTIVE: To determine sedative and cardiorespiratory effects of dexmedetomidine alone and in combination with butorphanol or ketamine in cats. DESIGN: Randomized crossover study. ANIMALS: 6 healthy adult cats. PROCEDURES: Cats were given dexmedetomidine alone (10 microg/kg [4.5 mg/lb], IM), a combination of dexmedetomidine (10 microg/kg, IM) and butorphanol (0.2 mg/kg [0.09 mg/lb], IM), or a combination of dexmedetomidine (10 microg/kg, IM) and ketamine (5 mg/kg [2.3 mg/lb], IM). Treatments were administered in random order, with > or = 1 week between treatments. Physiologic variables were assessed before and after drug administration. Time to lateral recumbency, duration of lateral recumbency, time to sternal recumbency, time to recovery from sedation, and subjective evaluation of sedation, muscle relaxation, and auditory response were assessed. RESULTS: Each treatment resulted in adequate sedation; time to lateral recumbency, duration of lateral recumbency, and time to recovery from sedation were similar among treatments. Time to sternal recumbency was significantly greater after administration of dexmedetomidine-ketamine. Heart rate decreased significantly after each treatment; however, the decrease was more pronounced after administration of dexmedetomidine-butorphanol, compared with that following the other treatments. Systolic and diastolic blood pressure measurements decreased significantly from baseline with all treatments; 50 minutes after drug administration, mean blood pressure differed significantly from baseline only when cats received dexmedetomidine and butorphanol. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in cats, administration of dexmedetomidine combined with butorphanol or ketamine resulted in more adequate sedation, without clinically important cardiovascular effects, than was achieved with dexmedetomidine alone.

Anesthetics, Dissociative↗

PubMed2005

Analgesic efficacy of preoperative administration of meloxicam or butorphanol in onychectomized cats.

OBJECTIVE: To determine analgesic efficacy and adverse effects of preemptive administration of meloxicam or butorphanol in cats undergoing onychectomy or onychectomy and neutering. DESIGN: Randomized controlled study. ANIMALS: 64 female and 74 male cats that were 4 to 192 months old and weighed 1.09 to 705 kg (2.4 to 15.5 lb). PROCEDURE: Cats received meloxicam (0.3 mg/kg [0.14 mg/lb], s.c.) or butorphanol (0.4 mg/kg [0.18 mg/lb], s.c.) 15 minutes after premedication and prior to anesthesia. A single blinded observer measured physiologic variables, assigned analgesia and lameness scores, and withdrew blood samples for each cat at baseline and throughout the 24 hours after surgery. Rescue analgesia (butorphanol, 0.4 mg/kg, i.v. or s.c.) or administration of acepromazine (0.025 to 0.05 mg/kg [0.011 to 0.023 mg/lb], i.v.) was allowed. RESULTS: Meloxicam-treated cats were less lame and had lower pain scores. Cortisol concentration was higher at extubation and lower at 1, 5, and 12 hours in the meloxicam-treated cats. Fewer meloxicam-treated cats required rescue analgesia at 3, 5, 12, and 24 hours after extubation. General impression scores were excellent or good in 75% of meloxicam-treated cats and 44% of butorphanol-treated cats. There was no treatment effect on buccal bleeding time; PCV and BUN concentration decreased in both groups, and glucose concentration decreased in meloxicam-treated cats. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative administration of meloxicam improved analgesia for 24 hours without clinically relevant adverse effects in cats that underwent onychectomy or onychectomy and neutering and provided safe, extended analgesia, compared with butorphanol.

Analgesics, Non-Narcotic↗

PubMed1999

kappa-Opioid receptor effects of butorphanol in rhesus monkeys.

Butorphanol and nalbuphine have substantial affinity for mu and kappa-opioid receptor sites, yet their behavioral effects in monkeys are largely consistent with a mu receptor mechanism of action. Using ethylketocyclazocine (EKC) discrimination and diuresis assays in rhesus monkeys (Macaca mulatta), the purpose of the current investigation was to characterize the in vivo kappa-opioid activity of these compounds through the use of an insurmountable mu-opioid receptor antagonist, clocinnamox. Alone, butorphanol (0.001-0.032 mg/kg i.m.) failed to generalize to EKC, and pretreatment with the competitive opioid receptor antagonist quadazocine (0.1 or 0.32 mg/kg i.m.) did not alter this generalization. At 24 h after clocinnamox (0.1 mg/kg i.m.) administration, butorphanol fully generalized to EKC, and this generalization was maintained in two of three monkeys at 72 h. Parallel results were observed in diuresis: butorphanol alone and in the presence of quadazocine (1 mg/kg i.m.) did not alter urine output, and a marked diuretic effect was demonstrated 24 h to 2 weeks after clocinnamox administration. Clocinnamox did not alter the discriminative stimulus or diuretic effects of nalbuphine or of the kappa-opioid receptor agonists EKC or U69593. These results are consistent with an in vivo agonist activity of butorphanol at kappa-opioid receptors that can only be demonstrated when an insurmountable antagonist has substantially eliminated the dominant receptor population through which it exerts its action.

Analgesics, Opioid↗

PubMed1999

Cardiorespiratory effects of a combination of medetomidine, midazolam, and butorphanol in dogs.

OBJECTIVE: To characterize cardiorespiratory effects for a combination of medetomidine, butorphanol, and midazolam and to compare magnitude of cardiorespiratory depression with that induced by a commonly used inhalation anesthetic regimen (acepromazine-butorphanol-thiopental-halothane). ANIMALS: 10 clinically normal dogs (2 groups of 5). PROCEDURE: In treated dogs, medetomidine was administered (time, 0 minutes); midazolam and butorphanol were administered when effects of medetomidine were maximal (time, 20), and atipamezole was administered subsequently (time 60). In control dogs, drugs were administered after allowing effects of each agent to be achieved: acepromazine was given at time 0, butorphanol and thiopental were administered at time 35, and halothane was administered from time 45 until 110. Various cardiorespiratory and hematologic variables were measured or calculated. RESULTS: Respiratory rate, arterial and venous pH, venous oxygen content, oxygen consumption, and oxygen delivery decreased significantly below baseline values for treated dogs; end-tidal CO2, arterial and venous P(CO)2, and O2 extraction increased significantly above baseline values. Compared with data obtained after anesthesia, arterial HCO3- concentration, venous P(O2) and S(O2), cardiac output, oxygen extraction, and oxygen delivery appeared more modified in treated dogs. Oxygen consumption and physiologic shunt fraction were less modified in treated dogs than control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine-butorphanol-midazolam combination induced respiratory depression, comparable in magnitude to that induced by a widely used inhalation anesthetic regimen. Respiratory variables remained within acceptable limits during anesthesia; however, those associated with cardiovascular function were more severely affected.

Acepromazine↗

PubMed1999

Effects of intramuscular administration of low doses of medetomidine and medetomidine-butorphanol in middle-aged and old dogs.

OBJECTIVE: To determine effects of low doses of medetomidine administered with and without butorphanol and glycopyrrolate to middle-aged and old dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 88 healthy dogs > or = 5 years old. PROCEDURE: Dogs were assigned randomly to receive medetomidine (2, 5, or 10 micrograms/kg [0.9, 2.3, or 4.6 micrograms/lb] of body weight, i.m.) alone or with glycopyrrolate (0.01 mg/kg [0.005 mg/lb], s.c.), medetomidine (10 micrograms/kg) and butorphanol (0.2 mg/kg [0.1 mg/lb], i.m.), or medetomidine (10 micrograms/kg), butorphanol (0.2 mg/kg), and glycopyrrolate (0.01 mg/kg). Anesthesia was induced with thiopental sodium and maintained with isoflurane. Degree of sedation and analgesia were determined before and after medetomidine administration. Respiratory rate, heart rate, and mean arterial blood pressure were determined 10 and 30 minutes after medetomidine administration. Adverse effects and amounts of thiopental and isoflurane used were recorded. RESULTS: Sedation increased after medetomidine administration in 79 of 88 dogs, but decreased in 7 dogs that received 2 or 5 micrograms of medetomidine/kg. Mean postsedation analgesia score and amounts of thiopental and isoflurane used were less in dogs that received medetomidine and butorphanol, compared with other groups. Respiratory rate, heart rate, and blood pressure were not different among groups. Significantly more adverse effects developed in dogs that did not receive glycopyrrolate. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of medetomidine (10 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.) induced sedation and analgesia and reduced amounts of thiopental and isoflurane required for anesthesia in middle-aged and old dogs. Glycopyrrolate decreased frequency of medetomidine-associated adverse effects.

Adjuvants, Anesthesia↗