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PubMed1995

Butorphanol: an opioid for day-care paediatric surgery.

The purpose of this study was to compare the side effects and efficacy of equianalgesic doses of morphine (M) and butorphanol (B) in children undergoing similar surgical procedures associated with moderate postoperative pain. We studied 156 healthy children aged 1.5-13 yr who underwent elective inguinal herniorrhaphy or orchidopexy. After induction of anaesthesia subjects were given 150 micrograms.kg-1 M or 30 micrograms.kg-1 B following a randomized, stratified, blocked and double-blind design. A standardized anaesthetic was administered, which included 1.5% halothane, vecuronium, droperidol and mechanical ventilation. The postsurgical four-hour follow-up included assessment of pain, vomiting and respiratory depression. Pain was assessed with mCHEOPS and analgesics were administered when indicated in the recovery room. Each opioid was administered to a group of 78 patients. Within each group, 25 subjects had an iv induction, 21 children had an orchidopexy and 57 had inguinal hernia repairs. The groups were similar with respect to age, weight, and length of surgery. The choice of opioid did not affect recovery times from anaesthesia. Analgesic requirements were similar among the groups. Ten minutes after arrival in the recovery room the B-subjects had a lower pain score than the M-patients. Postoperative vomiting was less among the B-subjects: 14% vs 28%, P = 0.03. Two M-patients required an unscheduled admission to hospital because of vomiting. It is concluded that butorphanol has few advantages over morphine in the population studied.

Adolescent↗

PubMed1985

Butorphanol and nalbuphine: a pharmacologic comparison.

The agonist/antagonist analgesics, butorphanol (Stadol) and nalbuphine (Nubain), are being increasingly employed as intravenous sedation agents; nalbuphine will be available in the future as an oral analgesic. The drugs possess numerous pharmacologic similarities and some dissimilarities. Both are equianalgesic (and nalbuphine is equipotent) with morphine parenterally and codeine orally. Their pharmacokinetics are similar; nalbuphine has a longer duration of action. Both may precipitate an abstinence syndrome in narcotic-dependent persons and will probably be associated with low-level drug abuse potential. They are both agonists of the kappa opioid receptor and partial agonists of the mu receptor. Butorphanol is a partial agonist of the sigma receptor responsible for psychotomimetic effects. The incidence of adverse effects is low, sedation being the most common. In cardiac-risk patients, nalbuphine does not increase cardiac work or oxygen requirements; nor do increasing doses of nalbuphine increase the duration of respiratory depression. Both drugs possess plateau respiratory depressant actions.

Anesthesia, Dental↗

PubMed1991

Analgesic activity and respiratory effects of butorphanol in sheep.

The analgesic drug butorphanol tartrate has proved useful clinically in horses and dogs but its analgesic profile had not yet been investigated in sheep. This study was initiated to determine the thermal and mechanical antinociceptive activity of butorphanol (at the dose rates 0.05, 0.1 and 0.2 mg kg-1) in sheep. The drug produced significant analgesia in the thermal test system, the duration of which was dose related but no significant elevation in mechanical pressure thresholds could be detected. In a further set of experiments the dose rate was increased to 0.4 mg kg-1 and mechanical testing was repeated. There was still no clinically significant elevation in pressure thresholds. At a dose rate of 0.2 mg kg-1 the drug had no detectable effect on respiratory blood gas tensions. Behavioural changes were severe if a dose rate of 0.2 mg kg-1 was exceeded.

Analgesia↗

PubMed1996

Quantitative determination of butorphanol and its metabolites in human plasma by gas chromatography-electron capture negative-ion chemical ionization mass spectrometry.

Two separate analytical methods have been developed for the determination of butorphanol and its metabolites in human plasma. One method is specific for butorphanol (I) while the other determines the metabolites, hydroxybutorphanol (II) and norbutorphanol (III). Both procedures incorporate solid-phase extraction, chemical derivatization and separation, and detection using gas chromatography-electron-capture negative-ion chemical ionization mass spectrometry (GC-ECNCI-MS). Both methods use the cyclopropyl analog of I (BC-2605, IV) as the internal standard and the procedures for extraction of the analytes from plasma are identical. However, following extraction, either the pentafluorobenzoyl ester of I or the tris and bis-trifluoroacetyl esters of II and III, respectively, were prepared. The derivatives were analyzed by GC-ECNCI-MS with selected-ion monitoring of the molecular ions. The standard curves were linear over the concentration ranges of 20-2000, 20-1000 and 50-1000 pg/ml for I, II and III, respectively. All standard curves from the assay validation had r2 values of > or = 0.994, 0.991 and 0.985 for I, II and III, respectively. For all three compounds, the intra- and inter-assay precisions (C.V.) and inter-assay accuracy (deviation from nominal) were within 12% for plasma quality control samples. All derivatives were stable in the reconstitution solvent for at least 24 h. The assays are being used for the determination of plasma concentrations of I, II and III in humans following repeated administration of nasal spray.

Area Under Curve↗

PubMed2005

High-performance liquid chromatography of nalbuphine, butorphanol and morphine in blood and brain microdialysate samples: application to pharmacokinetic/pharmacodynamic studies in rats.

A rapid and sensitive assay for quantification of nalbuphine, butorphanol and morphine in blood (50 microL) and brain microdialysate ( approximately 40 microL) samples was developed. Blood samples were extracted with ethyl acetate. Analysis was performed with high-performance liquid chromatography (HPLC) coupled to an electrochemical detector. The mobile phase was a mixture of 0.1 M sodium phosphate buffer, methanol and octane-sulfonic acid with ratio and pH depending on compound and matrix. The limits of quantification in blood samples were 25, 50 and 25 ng/mL for nalbuphine, butorphanol and morphine, respectively and 0.5 ng/mL for morphine in microdialysate samples. Based on sample volume, sensitivity and reproducibility, these assays are particularly suitable for pharmacokinetic/pharmacodynamic studies in rodents.

Animals↗

PubMed2001

The kappa-opioid antagonist GNTI reduces U50,488-, DAMGO-, and deprivation-induced feeding, but not butorphanol- and neuropeptide Y-induced feeding in rats.

Antagonists selective for either kappa- [e.g. nor-binaltorphimine (nor-BNI)] and mu- (e.g. beta-funaltrexamine) opioid receptors have previously been shown to reduce both kappa- and mu-opioid-induced feeding. In the present studies, the anorectic effects of GNTI, a newly synthesized antagonist selective for kappa-opioid receptors, were studied in rats. GNTI (0.032-0.32 nmol; i.c.v.), administered 15 min prior to food access, reduced feeding induced by the kappa-opioid agonist U50,488 (producing a 70% maximal decrease), the mu-opioid agonist DAMGO (90% maximal decrease), and 24 h acute food deprivation (60% maximal decrease). GNTI did not reduce the orexigenic effects of butorphanol, an agonist that binds to both kappa- and mu-opioid receptors, and neuropeptide Y (NPY). Taken together, these results suggest that GNTI is a potent anorectic agent and opioid antagonist in rats. Like nor-BNI, GNTI reduced feeding induced by both kappa- and mu-opioid agonists. However, unlike nor-BNI, GNTI did not alter the orexigenic effects of butorphanol or NPY. Given the selectivity of GNTI and its effectiveness in several of the present experiments, its potency, and its short duration of action compared to nor-BNI, GNTI may serve to be a useful tool to study behavioral effects mediated by kappa-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMedDate not supplied

Butorphanol and nalbuphine in opioid-dependent humans under a naloxone discrimination procedure.

Opioid-maintained volunteers were trained to distinguish between a low dose of the opioid antagonist naloxone (0.15 mg/70 kg, i.m.; i.e., Drug A) and placebo (i.e., Drug B) under an instructed novel-response drug-discrimination procedure in which subjects identify the drug condition as "A," "B," or "N" (neither A nor B--'novel'). Once the discrimination was acquired, doses of naloxone (000.15 mg/70 kg, i.m.) and the mixed-action opioid agonist/antagonists butorphanol (0-1.5 mg/70 kg, i.m.) and nalbuphine (0-3.0 mg/70 kg, i.m.) were tested. Naloxone produced dose-related increases in naloxone-appropriate responding with little or no 'novel'-appropriate responding. Butorphanol produced a dose-related increase in naloxone- and 'novel'-appropriate responding, occasioning approximately 70% and 29%, respectively, at the highest dose tested. Nalbuphine produced 40-65% naloxone-appropriate responding at all doses tested and 33% 'novel'-appropriate responding at the highest doses. Self-reported effects produced by each agent differed only slightly. These results suggest that mixed-action opioid agonist/antagonists may be distinguished from the opioid antagonist naloxone based on their discriminative-stimulus effects under a novel-response naloxone discrimination procedure.

Adult↗

PubMed1997

Determination of butorphanol in horse race urine by immunoassay and gas chromatography-mass spectrometry.

An analytical procedure to screen butorphanol in horse race urine using ELISA kits and its confirmation by GC-MS is described. Urine samples (5 ml) were subjected to enzymatic hydrolysis and extracted by solid-phase extraction. The residues were then evaporated, derivatized and injected into the GC-MS system. The ELISA test (20 microl of sample) was able to detect butorphanol up to 104 h after the intramuscular administration of 8 mg of Torbugesic, and the GC-MS method detected the drug up to 24 h in FULL SCAN or 31 h in the SIM mode. Validation of the GC-MS method in the SIM mode using nalbuphine as internal standard included linearity studies (10-250 ng/ml), recovery (+/-100%), intra-assay (4.1-14.9%) and inter-assay (9.3-45.1%) precision, stability (10 days), limit of detection (10 ng/ml) and limit of quantitation (20 ng/ml).

Analgesics, Opioid↗

PubMed1998

Effects of amphetamine, butorphanol, and morphine pretreatment on the maintenance and reinstatement of cocaine-reinforced responding.

Three groups of rats (N = 23) self-administered intravenous cocaine (0.4 mg/kg/infusion) during the initial 2 hr of daily 7-hr sessions. During the remaining 5 hr of these sessions, responding produced saline infusions. On test days, each rat was pretreated with an assigned dose of either butorphanol, morphine, amphetamine, or saline before the self-administration session followed by a priming injection of cocaine (3.2 mg/kg i.v.) or saline at the beginning of the 4th hr. Results showed that both amphetamine (0.5, 1.0, and 2.0 mg/kg) and morphine (0.3, 1.0, and 2.0 mg/kg) pretreatment dose-dependently reduced cocaine self-administration whereas only amphetamine affected (increased) reinstatement responding. Butorphanol pretreatment (8 mg/kg) suppressed cocaine self-administration and blocked the effect of the cocaine priming injections on pretreatment testing days. These findings indicate that (a) pretreatment drugs with similar stimulus properties potentiate reinstatement of responding and (b) pretreatment drugs can differentially affect maintenance and reinstatement of responding.

Amphetamine↗

PubMed1998

The pharmacodynamics of thiopental, medetomidine, butorphanol and atropine in beagle dogs.

This study evaluated the quality of anaesthesia and some of the haemodynamic effects induced by a combination of thiopental, medetomidine, butorphanol and atropine in healthy beagle dogs (n = 12). Following premedication with atropine (ATR, 0.022 mg/kg intravenously (i.v.)) and butorphanol (BUT, 0.22 mg/kg i.v.), medetomidine (MED, 22 micrograms/kg intramuscularly (i.m.)) was administered followed in 5 min by thiopental (THIO, 2.2 mg/kg i.v.). Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) were monitored continuously with an ECG and direct arterial blood pressure monitor. Atipamezole (ATI, 110 micrograms/kg i.v.) was administered to half of the dogs (n = 6) following surgery to evaluate the speed and quality of arousal from anaesthesia. Anaesthesia was characterized by excellent muscle relaxation, analgesia and absence of purposeful movement in response to surgical castration. Arousal following antagonism of medetomidine was significantly faster (P < 0.05) than in unantagonized dogs. Recoveries were smooth but recovery times following atipamezole administration were highly variable among dogs (sternal time range 6-38 min, standing time range 9-56 min). Medetomidine caused a significant (P < 0.05) increase in SBP, DBP and MBP. Atropine prevented the medetomidine induced bradycardia. In conclusion, this combination provided adequate surgical anaesthesia in healthy beagle dogs. At the dosages used in this study, it seems prudent that this combination should be reserved for dogs free of myocardial disease.

Adjuvants, Anesthesia↗

PubMed2001

Comparison of sevoflurane with isoflurane for rapid mask induction in midazolam and butorphanol-sedated dogs.

Rapid mask induction can be a useful induction technique for veterinary patients, although it is often accompanied by exaggerated excitement responses in unpremedicated animals (Mutoh et al.: Jpn. J. Vet. Anesth. Surg. 26, 109-116; J. Vet. Med. Sci. 57, 1007-1013; J. Vet. Med. Sci. 57, 1121-1124; 1995). The aim of this study was to compare sevoflurane with isoflurane for rapid mask induction in six dogs sedated by a combination of midazolam (0.1 mg/kg) and butorphanol (0.2 mg/kg). Induction with sevoflurane (5%, 2.4 minimum alveolar concentration [MAC]) in O2 resulted in shorter time to loss of the palpebral reflex, negative tail clamp response, and successful intubation than with isoflurane (3%, 2.4 MAC) in O2. There were no changes in heart rate or mean arterial blood pressure during induction with sevoflurane, whereas an increase in heart rate was observed in dogs induced with isoflurane. A decrease in respiratory rate compared with the pre-induction rate was observed during induction, and associated mild respiratory acidosis, characterized by an increase in arterial PCO2, was measured at the end of the induction period in both induction groups. None of the animals had episodes of induction-related complications. These results suggest that both sevoflurane and isoflurane produce a smooth onset of induction in midazolam and butorphanol-sedated dogs. Sevoflurane is a more suitable for rapid mask induction than isoflurane since it provides faster induction associated with a lower blood/gas partition coefficient.

Anesthesia, Inhalation↗

PubMed2002

Effect of medetomidine-butorphanol-ketamine anaesthesia and atipamezole on heart and respiratory rate and cloacal temperature of domestic pigeons.

The purpose of this study was to evaluate the sedative-anaesthetic effects of a combination of medetomidine (M, 50 microg per pigeon), butorphanol (B, 50 microg per pigeon) and ketamine (K, 25 mg per pigeon) in domestic pigeons. Eight domestic pigeons (four male and four female, 8-15 months old) were used. The combination of Medetomidine and butorphanol injectable solutions were used to produce sedation. Ten minutes after M + B administration, K was injected. The anaesthetic effects of the drugs were reversed by administration of Atipamazole (AT) at 60 min after K administration. All drugs were injected into the pectoral muscles. The sedative-anaesthetic effects of the M + B-K combination and, alterations in respiratory rate (RR), heart rate (HR), electrocardiographic (ECG) findings and cloacal temperature (CT) were investigated before and 10 min after pre-medication with M + B, at 5, 15, 30, 45 and 60 min during the onset of K anaesthesia and at 1, 5, 10, 20, 30 and 60 min following the administration of AT. The HR and RR of pigeons decreased within 10 min following M + B administration and remained lower until 1st and 5 min of AT injection, respectively. In ECG, no significant alterations in P, Q, R and S-values were observed, however, arhythmia was recorded for three pigeons, which returned to normal values following AT administration throughout the measurement. Cloacal temperature decreased gradually during the anaesthesia from 41.0 to 32.7 degrees C. The drug combination used in this study produced a satisfactory general anaesthesia for seven of the eight pigeons. All pigeons were unconscious within 5 min after K administration as indicated by disappearance of the palpebral and corneal reflexes and lack of reaction to the pain stimuli during the study. The effect of AT administration was observed within 10 min as all pigeons responded partly against stimuli and all reflexes. It is concluded that M + B-K anaesthesia in pigeons is a safe and reliable anaesthetic protocol for surgery.

Adrenergic alpha-Antagonists↗

PubMed2000

Continuous epidural butorphanol relieves pruritus associated with epidural morphine infusions in children.

We examined the efficacy of epidural butorphanol to either prevent or relieve pruritus associated with epidural morphine infusion in children. Forty-six children were randomized to receive either epidural morphine (M) or epidural M with butorphanol (B) for postoperative analgesia. They received bupivacaine and either M 50 microg.kg-1 or the same dose of M plus B 10 microg.kg-1. Following surgery, a continuous infusion of 0.1% bupivacaine with either M 20 microg.ml-1 or M 20 microg.ml-1 + B 4 microg.ml-1 was given at a rate of 0.3 ml.kg-1.h-1. Pain scores and pruritus scores were recorded every 4 h during epidural infusion. Subjects with a pruritus score=2 received diphenhydramine 0.5 mg.kg-1 i.v. and were switched to an alternate epidural infusion; subjects receiving M (group M) were switched to M+B while subjects receiving M+B (group B) were switched to hydromorphone (H) 4 microg.ml-1. There was no difference in the initial incidence of pruritus (group M 11/18; group B 13/28). No subject in group M required a second change of epidural infusion because of continued pruritus after being switched to M+B; five of 13 subjects in group B continued to experience pruritus after being switched to H and required a second change of epidural infusion or an alternate analgesic modality (P=0.038). The median pruritus score in the first 24 h after changing epidural infusions was 0 in subjects in group MDelta (changed from M to M+B) and 1 in subjects in group BDelta (changed from M+B to H; P=0.012). While the median sedation score in the first 24 h was 1 in both groups, there was a greater incidence of sedation scores of 2 in group B than group M (28% vs 12.3%; P=0.021). B 10 microg.kg-1 was not effective in preventing pruritus associated with bolus epidural administration of M 50 microg.kg-1 in children. B 1.2 microg.kg-1. h-1 was effective in relieving pruritus associated with continuous epidural infusion of M 6 microg.kg-1.h-1.

Adolescent↗

PubMed1999

Use of midlatency auditory-evoked potentials as indicator of unconsciousness in the dog: characterisation of the effects of acepromazine-thiopentone, medetomidine-thiopentone and medetomidine-butorphanol-midazolam combinations.

Middle latency auditory-evoked potentials were measured in sedated and anaestetised dogs to determine their possible usefulness in monitoring of unconsciousness during anaesthesia and to compare the effects of anaesthetic protocols. There were three groups of five dogs: group I received acepromazine; groups 2 and 3 received medetomidine; 30 minutes later, groups 1 and 2 received thiopentone and group 3 received midazolam and butorphanol. Groups 2 and 3 received atipamezole 60 minutes after medetomidine was administered. Auditory-evoked potentials were recorded at time 15, 40 and 75 minutes. Thiopentone administration resulted in a profound modification of the pattern of response, and several peaks were no longer identified. In group 3, the administration of midazolam-butorphanol tended to increase the latency of the different peaks, but lesser than thiopentone did. Middle latency-evoked potentials appeared to be potentially useful in the monitoring of unconsciousness in the dog.

Acepromazine↗

PubMed2000

The effects of ovariohysterectomy plus different combinations of halothane anaesthesia and butorphanol analgesia on behaviour in the bitch.

One hundred and sixty-six behaviours were identified as possible indices of post-operative pain-induced distress in the bitch. These were assessed in bitches after treatment with different combinations of halothane and butorphanol in the absence of surgery and following ovariohysterectomy under halothane anaesthesia with or without butorphanol analgesia given at different stages during the operation. Behaviour was monitored while the bitches were alone (non-interactive) and when routinely examined and handled prior to blood sampling (interactive). Seventy-six of the 166 behaviours occurred so infrequently (less than two occurrences per hour) as to be of no value as indices. Non-interactive behaviours associated with surgery were a decrease in normal speed cage circling and an increase in drawing the rear limbs up in the pike position. The infrequent non-interactive behaviours of incision licking, vomiting and flank gazing were considered to be expressions of pain caused by ovariohysterectomy. During the post-surgical period, bitches given analgesic moved less frequently than those not receiving analgesic. Vocalisation was associated with dysphoria of analgesia rather than pain-induced distress. The behaviour of bitches after ovariohysterectomy suggests that this is a painful procedure which warrants analgesia.

Analgesics, Opioid↗

PubMed1983

Polarographic determination of butorphanol tartrate.

A new indirect polarographic method is proposed for the determination of butorphanol tartrate in the injectable solution form (Stadol). Direct-current polarography and differential pulse polarography (DPP) were applied for the study of authentic butorphanol and its injectable solution form in alkaline medium after nitration with 1 M potassium nitrite in presence of 1 M hydrochloric acid. The standard addition method was employed for the evaluation of the results and the mean percentage found for the injectable solution form was 99.2 +/- 1.0.

Butorphanol↗

PubMed1997

A comparative study of medetomidine-butorphanol-ketamine and medetomidine-ketamine anaesthesia in dogs.

The anaesthetic and cardiopulmonary effects of medetomidine (20 micrograms/kg)-butorphanol (0.1 mg/kg)-ketamine (MBK) (2.5, 5.0, 7.5 mg/kg) and medetomidine (40 micrograms/kg)-ketamine (5.0 mg/kg) (MK) were compared in dogs. The induction time (time from the initial injection of the sedative to lateral recumbency) by medetomidine-butorphanol (6.0 +/- 2.3 min) was significantly shorter than that by medetomidine alone (10.4 +/- 2.9 min). The duration of anaesthesia induced by MK was shorter than that by MBK2.5. The analgesic effects of MBK were more potent than those of MK. Mean arterial blood pressure increased significantly after administration of the sedatives, and then decreased to base-line value after the ketamine injection and remained stable throughout the experimental period. Respiratory rate decreased gradually after the administration of each sedative and was depressed until 60 min after the ketamine injection. MBK anaesthesia is effective and widely available for therapeutic procedures depending upon the selection of the ketamine dose.

Analgesics, Opioid↗

PubMedDate not supplied

A clinical comparison of oxymorphone-acepromazine and butorphanol-acepromazine sedation in dogs.

Oxymorphone (0.2 mg/kg, maximum 4.5 mg) or butorphanol (0.2 mg/kg, maximum 4.5 mg), with acepromazine (0.05 mg/kg) and atropine (0.02 mg/kg), was administered intravenously to 106 healthy dogs undergoing radiographic examination of the pelvis. The dogs were returned to their owners after the examination and opioid reversal with naloxone (0.02 mg/kg intravenously, maximum 0.4 mg). Questionnaires were completed by the radiology staff and owners of the dogs, and results were coded by one person, all of whom were unaware of the treatment used. There was a lower incidence of temporary excitement upon injection and less panting in dogs sedated with butorphanol than with oxymorphone. There were no significant differences in degree of sedation, response to noise or manipulation, vocalization, defecation, heart rate, reversibility, sedation after reversal, or personality. Both forms of chemical restraint were satisfactory for radiographic examination of the pelvis, with no significant side effects in healthy dogs.

Acepromazine↗