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PubMed2003

A comparison of the analgesic effects of butorphanol with those of meloxicam after elective ovariohysterectomy in dogs.

This study was designed to compare the analgesic effects of butorphanol with those of meloxicam following ovariohysterectomy. Fifteen dogs were premedicated with 0.05 mg/kg body weight (BW) of acepromazine by intramuscular (IM) injection, plus 0.2 mg/kg BW of meloxicam by subcutaneous (SC) injection. Fifteen dogs were premedicated with 0.05 mg/kg BW of Acepromazine, IM, plus 0.2 mg/kg BW of butorphanol, IM. Anesthesia was induced with thiopental, and dogs were maintained on halothane. All pain measurements were performed by 1 experienced individual, blinded to treatment. Pain scores and visual analogue scales (VAS) were performed at 2, 3, 4, 6, 8, 12, and 24 hours postpremedication. An analgesiometer was used to determine the pressure required to produce an active avoidance response to pressure applied at the incision line. Pain scores, VAS, and analgesiometer scores were analyzed by using a generalized estimating equations method. A significance level of P < 0.05 was considered significant. Animals that received meloxicam demonstrated significantly lower pain scores and VAS than did animals that received butorphanol in the first 12 hours after surgery. Results of this study suggest that meloxicam will produce better postoperative analgesia than will butorphanol. Mucosal bleeding times were performed on cooperative animals in the study group (11 butorphanol, 13 meloxicam). Bleeding times were performed prior to premedication, 6 hours following premedication, and 24 hours after premedication. The 6- and 24-hour readings were compared with baseline bleeding times by using a paired t-test with a Bonferroni correction (a significance level of P < 0.025). Bleeding times did not change significantly over time.

Analgesics, Non-Narcotic↗

PubMed1991

Effects of butorphanol on luteinizing hormone and follicle stimulating hormone levels in ovariectomized rats--comparative study with morphine sulphate.

Studies were conducted into the effects on pituitary gonadotrophic hormones in ovariectomized rats of butorphanol, a synthetic morphine derivative which was claimed to be a potent analgesic with few side-effects, in comparison to effects of the naturally occurring alkaloid morphine. For this purpose, 3 groups of ovariectomized rats were used. Rats of the 1st group were injected butorphanol at 2 dose levels (1 or 2 mg/kg body weight [b.w.]. Those of the 2nd group were injected morphine sulphate (10 or 20 mg/kg b.w.). The 3rd group was injected saline and served as control. Blood samples were collected by orbital sinus punctures, just before treatment and 1 hour post injection. Luteinizing hormone (LH) and follicle-stimulation hormone levels were determined in the sera of rats by radio-immuno-assay. The results revealed that morphine, at the 2 dose levels used, produced more than 90% decrease in serum LH concentration, whereas butorphanol produced more than 70% decrease in serum LH levels. Both morphine and butorphanol, at the 2 doses used, produced more than 76% decrease in serum follicle stimulating hormone concentration. It is concluded that butorphanol, the morphinic derivative, has a depressive effect on the synthesis and/or release of gonadotrophic hormones. This inhibitory effect, however, was nearly as potent as that produced by morphine sulphate.

Animals↗

PubMed1991

Butorphanol tartrate (stadol): a review.

Butorphanol tartrate (Stadol; Anaquest, Madison, WI/Bristol-Meyers Squibb, Evansville, IN) is an analgesic possessing mixed agonist-antagonist activity at opiate receptors. Receptor specificity has been used to limit respiratory depression, gastrointestinal side effects, and reduce the risk of dependency. Theoretically it offers an advantage over traditional opiates such as morphine and meperidine in the treatment of moderate pain. Butorphanol has been used as a preoperative sedative and analgesic, as a supplement to balanced anesthesia, and for suppression of postanesthesia shaking. Other recognized uses include obstetric analgesia during labor and relief of moderate postpartum pain. In addition, butorphanol has been used effectively for conscious sedation. Its lack of euphoric effects may be useful in emergency medicine for clinical populations prone to drug-seeking behavior. Butorphanol has been used more recently for epidural analgesia or for intravenous patient-controlled analgesia when allergies to opiates exist. Since butorphanol is not a controlled substance, its use can reduce administrative liability for abuse and can lower the number of distribution records associated with Schedule II narcotics.

Butorphanol↗

PubMed1991

Dose effectiveness and safety of butorphanol in acute migraine headache.

This study was undertaken to compare the effectiveness and safety of three dosage levels of butorphanol in 52 patients with acute, severe migraine headache. After baseline evaluation, patients were given a dose of butorphanol 1.0, 2.0, or 3.0 mg intramuscularly on a double-blind basis. Assessments of pain intensity and pain relief using 100 mm linear analog scales (LAS), vital signs, and medication side effects were made at 15, 30, 45, and 60 minutes after the dose. All three treatment groups were similar in baseline characteristics. Each dose of butorphanol demonstrated a significant decrease in pain intensity LAS compared to baseline and increase in pain relief LAS over the observation period. The majority of analgesic response was observed at the first (i.e., 15-min) assessment. Doses of 2.0 and 3.0 mg produced significantly greater analgesia than did 1.0 mg at all posttreatment evaluations. No significant difference was apparent between the 2.0- and 3.0-mg doses. Adverse cardiovascular and respiratory depressant effects were not observed. An analgesic response to butorphanol 2.0 and 3.0 mg is clearly and rapidly evident and near maximum 30-45 minutes after administration. We conclude that in these doses butorphanol provides effective and safe analgesia for patients with acute migraine headache.

Acute Disease↗

PubMed1988

Butorphanol-precipitated withdrawal in opioid-dependent human volunteers.

The subjective, physiological and behavioral effects of hydromorphone, naloxone and butorphanol, an opioid agonist/antagonist analgesic, were studied in adult, male, methadone-dependent volunteers living on a clinical research ward. Drug conditions included saline placebo, 4 and 8 mg of hydromorphone HCl, 0.375, 0.75, 1.5, 3 and 6 mg of butorphanol tartrate and 0.1 and 0.2 mg of naloxone HCl. Drug conditions, given by i.m. injection, were tested in five subjects under double-blind conditions in 2.5-hr experimental sessions. Physiologic measures and subject- and observer-rated behavioral responses were measured before dosing and for 2 hr after drug administration. Hydromorphone decreased pupil diameter, and significantly increased ratings of "Good Effects" on the subjective measures. Naloxone precipitated opioid abstinence which was measurable on several subject- and observer-rated behavioral measures and physiological measures. Butorphanol produced effects which were generally similar to the effects of naloxone, indicating that butorphanol doses precipitate withdrawal signs and symptoms when administered to methadone-dependent humans. There were some differences in the withdrawal syndromes precipitated by naloxone vs. butorphanol, suggesting that multiple mechanisms may be involved in opioid withdrawal precipitation.

Adult↗

PubMedDate not supplied

Epidural morphine or butorphanol augments bupivacaine analgesia during labor.

To determine the efficacy and the safety of epidural morphine or butorphanol combined with bupivacaine, 40 healthy parturients were studied during labor and delivery. All patients received an epidural test dose of 2 ml of 0.5% bupivacaine. Patients were then randomly assigned to receive one of four epidural regimens in a double-blind fashion: 0.25% bupivacaine + 1 mg butorphanol (Group I), 0.25% bupivacaine + 2 mg butorphanol (Group II), 0.25% bupivacaine + 2 mg morphine (Group III), or 0.25% bupivacaine alone (Group IV). Each group consisted of ten patients. All subsequent epidural injections were with plain 0.25% bupivacaine. Duration of analgesia was significantly longer for groups I, II, and III when compared to group IV (p less than or equal to .01); 139 +/- 111, 141 +/- 14, 199 +/- 29, and 96 +/- 6 minutes, X +/- SEM respectively. Quality of analgesia was significantly better in groups I, II, and III when compared with group IV. There were no differences between groups in duration of first and second stages of labor, uterine activity, or method of delivery. Thirty percent of patients in the morphine group (group III) developed mild pruritus that did not require any treatment. All neonates were vigorous at 5 minutes and had good Apgar Scores, umbilical cord acid base status, and Neurological Adaptive Capacity Scores. The authors conclude that adding small doses of either morphine or butorphanol to epidural bupivacaine during labor is effective and safe. Butorphanol may be preferable since none of the patients experienced pruritus.

Adult↗

PubMed1989

Effects of butorphanol tartrate on arterial pressure, jejunal blood flow, vascular resistance, O2 extraction, and O2 uptake in halothane-anesthetized ponies.

The effects of butorphanol tartrate on arterial pressure, jejunal blood flow, vascular resistance, oxygen extraction, and oxygen uptake were determined in 10 anesthetized ponies ventilated with a mixture of halothane and 100% oxygen, using isolated autoperfused jejunal segments. Physiologic saline solution or butorphanol tartrate (0.2 mg/kg of body weight) was administered as a single bolus into the left jugular vein. By 2 minutes, butorphanol decreased arterial blood pressure and intestinal blood flow, and increased intestinal oxygen extraction. However, intestinal vascular resistance and oxygen uptake were unaffected. Results of this study indicate that butorphanol tartrate induces a hypotension that secondarily decreases intestinal blood flow, but intestinal vascular resistance and metabolism are not adversely affected. We conclude that butorphanol tartrate does not compromise intestinal viability in halothane-anesthetized ponies and, therefore, may be a good analgesic choice for the equid destined for abdominal surgery.

Anesthesia, General↗

PubMed1989

[The sedative effects of a low dose of butorphanol combined with diazepam during spinal-epidural anesthesia (H-type anesthesia)].

The sedative effects of the low dose of butorphanol combined with diazepam during spinal-epidural (H-type) anesthesia were studied in 20 urological or gynecological patients of ASA class I or II. Patients were premedicated with 0.5mg of atropine sulfate and 50mg of hydroxyzine hydrochloride 1 hour before the operation. Spinal anesthesia was performed with 2.4 ml of 0.3% dibucaine or 2.5 ml of 3% lidocaine and if necessary 1-2% mepivacaine was administered via the catheter for maintenance of the epidural anesthesia. Butorphanol 0.5 mg and diazepam 5 mg were administered intravenously after the establishment of spinal anesthesia. We observed the condition of sedative effects, the changes in blood pressure, heart rate and respiratory rate, before the administration of butorphanol, 2 and 5 minutes after the administration of the drug and then every 5 minutes until the recovery was noticed. We found that the sedative effects of butorphanol combined with diazepam were clinically sufficient. Patients were sleeping for 40 minutes and then drowsy for 30 minutes with sufficient sedation. There was no complication except slight respiratory suppression. Our results suggest that the butorphanol combined with diazepam is a useful method for the sedation during spinal-epidural anesthesia.

Adult↗

PubMed1989

Epidural butorphanol-bupivacaine for analgesia during labor and delivery.

A double-blind, randomized, dose-response study of a combination of 0.25% bupivacaine combined with 0, 1, 2, or 3 mg of butorphanol was studied in 40 laboring parturients. The optimal dose of butorphanol combined with 8.5 to 10 ml 0.25% bupivacaine was 2 mg; with 2 mg, the duration of analgesia was significantly greater and the time to onset of analgesia significantly shorter than when no butorphanol was added, and the amount of bupivacaine could be reduced 50%. Adverse fetal effects were not observed except that of a low amplitude sinusoidal fetal heart rate pattern with doses of 3 mg butorphanol. All neonatal observations were normal. It is concluded that epidural butorphanol can be a useful and safe adjunct to bupivacaine used for epidural analgesia during labor.

Analgesia, Epidural↗

PubMed1988

Respiratory effects of high-dose butorphanol.

The effect of butorphanol on respiratory drive was assessed using a carbon dioxide response test (CRT). Eight male volunteers received 3 mg/70 kg of intravenous butorphanol every 30 min to a cumulative dose of 15 mg/70 kg (5 doses). Thirty minutes before the first butorphanol dose, each subject received normal saline to establish a baseline CRT. After each butorphanol dose, a CRT was repeated at 15 min to assess respiratory depression. Minute ventilation was plotted against PaCO2 to generate a regression line for saline and each dose. Slopes and intercepts for each line were calculated by least squares linear regression, and CRT displacement from saline was determined at each dose. The mean slope for each dose was not significantly different from the saline slope (p = 0.23-0.91). The mean displacement (+/- SEM) of the CRT from saline was greatest after the second dose (7.29 +/- 1.94 mm Hg) but not significantly different from the first or subsequent doses (p greater than 0.05). Butorphanol in doses of up to 15 mg/70 kg may have a 'ceiling effect' in respiratory depression.

Adult↗

PubMed1979

Comparative gastrointestinal and biliary tract effects of morphine and butorphanol (Stadol).

Butorphanol, levo-N-cyclobutylmethyl-3,14 beta-dihydroxy-morphinan, is a new agonist-antagonist type analgetic agent which is 4 to 8 times more potent than morphine in experimental animals and man. Butorphanol and morphine were evaluated in mice and dogs for their gastrointestinal and biliary tract smooth muscle effects. Morphine decreased the propulsion of a charcoal meal through the gastrointestinal tract of the mouse in a dose related manner with the maximal inhibition obtainable being 90%. Butorphanol produced a maximal inhibition of motility of only 40% with very high doses producing less of an inhibitory effect than lower doses. In dogs, morphine caused a dose-dependent increase in duodenal smooth muscle activity and a dose-dependent decrease in bile duct flow. A clinically effective i.v. dose of morphine (0.1 mg/kg) produced a statistically significant spasmogenic effect on dog biliary tract and gastrointestinal smooth muscle, while a clinically effective equianalgetic i.v. dose of butorphanol (0.025 mg/kg i.v.) had little or not effect on the biliary or gastrointestinal systems. These findings indicate that at equianalgetic doses, butorphanol should produce less constipation and less biliary tract and gastrointestinal smooth muscle spasm than morphine.

Analgesics↗

PubMed1996

Anesthesia induced in pigs by use of a combination of medetomidine, butorphanol, and ketamine and its reversal by administration of atipamezole.

OBJECTIVE: To develop an IM administrable anesthetic combination for pigs. DESIGN: Use of a combination of atropine, medetomidine, butorphanol, and ketamine (MB-K) was evaluated as an anesthetic regimen and compared with that of a combination of atropine, xylazine, butorphanol, and ketamine (XB-K). Cardiorespiratory effects of MB-K combination and use of atipamezole as a means of reversing anesthesia induced by MB-K were examined. ANIMALS: 18 castrated, mixed-breed, specific-pathogenfree pigs, aged 8 to 15 (mean, 12.1) weeks and weighing 14.5 to 26.0 (mean, 19.6) kg. were studied. PROCEDURE: Dosages of drugs used in this study were atropine, 25 micrograms/kg of body weight; medetomidine, 80 micrograms/kg; xylazine, 2 mg/kg; butorphanol, 200 micrograms/kg; ketamine, 10 mg/kg; and atipamezole, 240 micrograms/kg. RESULTS: MB-K combination proved to be more effective than XB-K combination as an anesthetic combination. After quick and smooth induction by IM administration, MB-K-induced anesthesia was sustained for 98.8 +/- 22.5 minutes (mean +/- SD, 47.4 +/- 16.5 minutes by XB-K) with accompanying muscular relaxation (91 +/- 18 minutes) and loss of pedal (82 +/- 24 minutes) and laryngeal (75 +/- 19 minutes) reflexes. Loss of these reflexes was of significantly longer duration than the loss induced by XB-K, enabled tracheal intubation, and, thus, supported major surgery for at least 30 minutes after induction. Recovery from MB-K-induced anesthesia was smooth. MB-K combination had a slight stimulative effect on cardiovascular status, and a significant depressant effect on blood gas and acid-base status, but these effects were within biologically acceptable limits. Oxygen consumption of pigs under MB-K-induced anesthesia decreased significantly. MB-K-induced anesthesia could be effectively and quickly reversed by IM or IV administration of atipamezole. CONCLUSIONS: The combination of medetomidine, butorphanol, and ketamine induces excellent surgical anesthesia in pigs, and results in moderate cardiorespiratory effects. A great advantage of the anesthetic regimen is that it can be effectively and quickly reversed by atipamezole. CLINICAL RELEVANCE: Medetomidine, butorphanol, and ketamine-induced anesthesia is available for short-term major surgery in pigs.

Adrenergic alpha-Antagonists↗

PubMed1996

Effects of a combination of detomidine and butorphanol on respiratory function in horses with or without chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the effects of detomidine and butorphanol in combination on respiratory function in horses and to determine whether these effects are more severe in horses with pre-existing respiratory dysfunction, DESIGN: Pulmonary function testing and arterial blood gas analyses were performed before and after administration of a combination of detomidine (10 micrograms/kg of body weight, i.v.) and butorphanol (20 micrograms/kg, i.v.). ANIMALS: 5 horses with chronic obstructive pulmonary disease and 5 horses free of respiratory disease (controls). PROCEDURES: Flow rates were obtained from a pneumotachograph attached to a face mask, and esophageal pressure was measured with a catheter placed in the distal third of the esophagus. Respiratory rate, tidal volume (VT), minute ventilation (VE), maximal change in transpulmonary pressure, pulmonary resistance, and dynamic compliance were calculated by use of a pulmonary function computer. Arterial blood was collected from the transverse facial artery, and blood gas partial pressures were measured with an automated blood gas analyzer. RESULTS: The combination of detomidine and butorphanol caused significant changes with time in respiratory rate, VT, VE, PaO2, and PaCO2. Changes with time in VT, VE, and maximal change in transpulmonary pressure were significantly different between groups. CONCLUSION: The combination of detomidine and butorphanol affects respiratory function in horses, and the observed changes are affected by the presence of pre-existing respiratory dysfunction. CLINICAL RELEVANCE: Changes in respiratory function after administration of a combination of detomidine and butorphanol are not necessarily more severe in horses with pre-existing respiratory dysfunction.

Airway Resistance↗

PubMed1993

The effects of butorphanol on baroreflex control of heart rate in man.

The effects of butorphanol injection on baroreflex control of heart rate were investigated using both pressor and depressor tests in eighteen adult patients. Baroreflex sensitivity was attenuated after butorphanol injection in the pressor test using phenylephrine, whereas it was unchanged in the depressor test using nitroglycerine. No resetting of the baroreflex occurred after butorphanol injection. After the administration of butorphanol, plasma epinephrine and norepinephrine levels increased. These results suggest that it is safe to use butorphanol clinically even when a reduction in blood pressure due to hypovolemia or unclamping of the major artery is expected and that it is disadvantageous to administer the drug when an increase in blood pressure due to cross-clamping of the major artery is predicted.

Journal Article↗

PubMed1978

Double-blind oral analgesic study of butorphanol in musculoskeletal pain: a comparison with codeine and placebo.

Butorphanol tartrate (4 mg and 8 mg) was compared to codeine phosphate (60 mg) and placebo for oral analgesic activity and side-effects employing a double-blind design in ninety-three out-patients suffering from moderate to very severe musculoskeletal pain. The study duration was 72 hours with medication administered every 4 to 6 hours (four times daily) for a total of twelve doses per patient. The results demonstrate that both the 4 mg and 8 mg doses of butorphanol were significantly better (p less than 0.u5) than placebo. While codeine 60 mg also proved active, it appears to be less efficacious than the high dose of butorphanol. The peak effect appeared to be evident in 1 to 2 hours. Butorphanol may be at least seven times more potent than codeine on a milligram basis. Although no serious side-effects were observed, butorphanol appeared to present a greater incidence of side-effects than codeine and placebo in this study.

Adolescent↗

PubMed1978

Effect of butorphanol and morphine on pulmonary mechanics, arterial blood pressure and venous plasma histamine in the anesthetized dog.

Butorphanol, levo-N-cyclobutylmethyl-3, 14beta-dihydroxy-morphinan, is a new agonist-antagonist type analgetic agent which is 4 times more potent than morphine in experimental animals. Equianalgetic doses of butorphanol and morphine were compared, following rapid intravenous injection to anesthetized dogs, for their effects on pulmonary resistance, dynamic compliance, arterial blood pressure and venous plasma histamine levels. Butorphanol, 0.75 mg/kg, had no effect on pulmonary resistance, dynamic compliance or venous plasma histamine levels. Morphine, 3 mg/kg, increased pulmonary resistance, decreased dynamic compliance and elevated venous plasma histamine levels. Both drugs decreased arterial blood pressure but the hypotensive effect of butorphanol was significantly less in magnitude than that of morphine. Pretreatment with chlorpheniramine antagonized the effects of morphine on pulmonary resistance, dynamic compliance and arterial blood pressure. These results suggest that in man butorphanol may have less potential than morphine for causing airway constriction, hypotension and histamine release.

Airway Resistance↗

PubMed1976

Antitussive properties of butorphanol.

Butorphanol (levo-N-cyclobutylmethyl-3, 14-dihydroxy morphinan), a potent analgetic agent of the narcotic antagonist type with a low abuse potential in laboratory animals, was evaluated for antitussive activity in unanesthetized guinea-pigs and dogs. Subcutaneously, it was over 100 times more active than codeine, dextromethorphan and dl-pentazocine and about 20 times more active than morphine in the guinea-pig, while in the dog it was 100, 10 and 4 times more active than codeine, dl-pentazocine and morphine, respectively. Orally, butorphanol was 15-20 times more active than either codeine or dextromethrophan in both species. Naloxone reversed the antitussive effects of butorphanol, codeine, morphine and dl-pentazocine while those of dextromethorphan were not antagonized. The antitussive effect of butorphanol and morphine lasted about 4 hr and both compounds were longer acting than codeine. Butorphanol was also shown to be as effective against cough of pathological origin as against experimentally induced cough in the dog.

Animals↗

PubMed1997

Premedication with the opioid analgesic butorphanol raises the threshold for ischemic preconditioning in dogs.

Elucidation of the subcellular mechanism of myocardial ischemic preconditioning should be facilitated by precise knowledge of the biology of the cardioprotective response. Any proposed molecular mechanism for preconditioning must be initiated during the required ischemic stress period. The studies reported in this paper were undertaken to determine whether the infarct-limiting effect of four 5-min episodes of ischemia interspersed by reperfusion can be achieved by a single 5-min episode. Adult open-chest mongrel dogs, premedicated with the analgesic butorphanol, and anesthetized with sodium pentobarbital, underwent occlusion of the circumflex coronary artery for 60 min, followed by reperfusion of 3 h. Treated dogs were preconditioned with one, two or four cycles of 5-min occlusion followed by reperfusion. Additional dogs, not premedicated with butorphanol, were either untreated (not preconditioned) or preconditioned with one cycle of ischemia. Infarcts were identified using triphenyl-tetrazolium chloride (TTC) macrochemistry and infarct size (as % of area-at-risk, AAR) was measured and analyzed (using analysis of covariance [ANCOVA]) with respect to coronary collateral blood flow (measured using radioactive microspheres). Four 5-min cycles of preconditioning ischemia markedly limited infarct size. Two cycles were as effective as four. In contrast, infarct size was not different from control infarct size after a single episode of preconditioning ischemia. However, when pentobarbital anesthesia was used without premedication with butorphanol, a single 5-min ischemic stress did induce cardioprotection. Thus, the ischemic stress required for myocardial preconditioning in dogs is dependent on the anesthetic and premedication protocol employed. A single 5-min stimulus is effective in dogs anesthetized with pentobarbital. Premedication with the opioid analgesic, butorphanol, increases the threshold for induction of cardioprotection.

Analgesics, Opioid↗