Combination Of Butorphanol Research Articles

BUTORPHANOL-AZAPERONE-MEDETOMIDINE FOR IMMOBILIZATION OF CAPTIVE WHITE-TAILED DEER

Drug combinations are commonly used to immobilize white-tailed deer (Odocoileus virginianus) for capture or handling. Although efficacy of various compatible and complementary drugs has been tested in clinical trials with deer, extensive negative side effects, impractical drug volume, and slow recovery from immobilization sometimes make these combinations less than ideal for routine field use. We hypothesized that a combination of butorphanol, azaperone, and medetomidine (BAM) would provide safe and effective immobilization of captive white-tailed deer while minimizing these complicating factors. We tested two dosages of this drug combination (BAM-1 and BAM-2) and two dosages of a naltrexone, tolazoline, and atipamezole antagonist combination (NTA-1 and NTA-2) with captive white-tailed deer. We characterized efficacy of drug for immobilization, quality of drug induction, and recovery after drug reversal, and we compared our findings with those of previous drug trials. Complete immobilization and excellent induction quality was achieved with a low volume dosage of BAM-2. Time to drug induction and deer recumbency for BAM-2 compared favorably with results from previous trials involving xylaxine/ ketamine and medetomidine/ketamine but without risk of hyperthermia. We found no differences in time to deer recovery for NTA-1 and NTA-2, with deer treated with either combination standing by 30 min postinjection. Regardless of immobilizing drugs used, we suggest practitioners monitor for signs of circulatory deficiency in deer and provide supplemental oxygen when needed.

BUTORPHANOL, AZAPERONE, AND MEDETOMIDINE ANESTHESIA IN FREE-RANGING WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) USING RADIOTRANSMITTER DARTS

Fourteen free-ranging white-tailed deer (Odocoileus virginianus) were successfully anesthetized for a total of 15 anesthetic events using a combination of butorphanol (mean+/-SD, 0.58+/-0.1 mg/kg), azaperone (0.37+/-0.06 mg/kg), and medetomidine (0.19+/-0.03 mg/kg) (BAM) administered by radiotelemetry darts from hunting blinds between November 2006 and May 2007. Mean time to locate deer (mean+/-SD, 17. 3+/-7 min), to recumbency (21.4+/-5 min), to initiation of data acquisition (27.5+/-8 min), total down time (37+/-6 min), and average distance run (161+/-82 m) were recorded. Physiologic monitoring was done every 5 min for a total of 20 min. Arterial blood gases were collected every 10 min. Mild to moderate hypoxemia and mildly depressed ventilation occurred in some animals. Muscle relaxation and plane of anesthesia were adequate for completion of all procedures; two deer were administered intravenous butorphanol supplementation to achieve light anesthesia (mean+/-SD, 0.19 mg/kg; 0.12 mg/kg). Recovery following intramuscular administration of naltrexone (1.34+/-0.42 mg/kg; 2x butorphanol dose) and atipamezole (0.93+/-0.14 mg/kg; 5x medetomidine dose) was rapid, smooth, and complete. Mean+/-SD recovery time was 4.5+/-1.5 min. Overall efficacy of the Pneu-Dart radiotelemetry system was 65%. Negative attributes of this protocol included long induction time and dart failure. No known mortalities occurred as a result of the study. This drug combination provided safe, reliable, short-term anesthesia of free-ranging white-tailed deer. Further evaluation for use in field procedures in other cervids is warranted.

Sedation and Pain Management with Intravenous Romifidine−Butorphanol in Standing Horses

The objective of this study was to determine the sedation, analgesia, and clinical reactions induced by an intravenous combination of romifidine and butorphanol in horses. The study was conducted on six saddle horses weighing 382 to 513 kg (mean ± SD; 449 ± 54 kg) and aged 6 to 14 years. The horses each underwent three treatments: intravenous romifidine 0.1 mg/kg body weight (RM; mean dose, 4.5 mL); intravenous butorphanol 0.05 mg/kg body weight (BT; mean dose, 2.4 mL); and intravenous romifidine 0.1 mg/kg body weight plus butorphanol 0.05 mg/kg body weight (RMBT; mean dose, 7.0 mL). The order of treatments was randomized. Heart rate, arterial pressure, respiratory rate, rectal temperature, sedation, and analgesia were measured at two times before treatments, 15 minutes apart (times –15 and 0) and at 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, and 180 minutes after drug administration. The onset of sedation was approximately 5 minutes after intravenous injection of RM and RMBT, whereas BT did not present this effect. The duration of complete sedation was approximately 60 minutes for RMBT and approximately 35 minutes for RM. The RMBT treatment provided 30 minutes and the RM treatment 20 minutes of complete analgesia. Heart rate decreased significantly ( P < .05) from basal values in the RM and RMBT treatments. Only RM caused significant decreases ( P < .05) in the respiratory rate. Arterial pressure did not change significantly ( P > .05) in any treatment. Intravenous administration of a romifidine−butorphanol combination to horses resulted in longer duration of sedation and analgesia than administration of romifidine or butorphanol alone. These effects probably resulted from a synergistic effect of the two drugs.

Pharmacokinetic - Pharmacodynamic Modeling of Analgesic Drugs in Beef Cattle

Bovine castration is performed on approximately 15 million cattle in the United States annually. Surgical castration with a scalpel followed by testicular removal using manual twisting (cattle&lt; 90 kg) or an emasculator (cattle &gt;90 kg) are the most common methods of castration performed in the USA. A survey of US veterinarians found that one in five practitioners report using analgesics or a local anesthetic at the time of castration. However, these drugs have not been formally approved by the FDA for pain relief. Validated methods of pain assessment are required in order to determine if analgesic drugs are efficacious. Potential pain assessment methods include plasma cortisol determination, plasma Substance P determination, accelerometers, thermography, chute exit speed, heart rate determination and electrodermal activity measurements. Studies have shown that a combination of butorphanol (0.01 - 0.025 mg/kg); xylazine (0.02 - 0.05 mg/kg) and ketamine (0.04 - 0.1 mg/kg) can mitigate these responses. Research is underway to further characterize the activity of analgesic drugs administered prior to castration.

Evaluation of Intramuscular Butorphanol, Azaperone, and Medetomidine and Nasal Oxygen Insufflation for the Chemical Immobilization of White-tailed Deer, Odocoileus virginianus

Chemical immobilization of wildlife often includes opioids or cyclohexamines. These substances are problematic as a result of their required storage, handling, and record-keeping protocols. A potentially useful alternative sedation protocol includes a combination of butorphanol, azaperone, and medetomidine (BAM: 0.43 mg/kg butorphanol, 0.36 mg/kg azaperone, 0.14 mg/kg medetomidine). One risk of wildlife immobilization with any drug combination is hypoxemia. This may be of particular importance when using an alpha 2 agonist such as medetomidine because of its powerful vasoconstrictive effect. In this prospective study, the BAM combination was evaluated for chemical immobilization of white-tailed deer. Additionally, selected physiologic parameters associated with BAM immobilization, including oxygen saturation via pulse oximetry and arterial blood gas measurement, with and without nasal insufflation of oxygen at a relatively low flow of 3 L/min, were evaluated. The BAM combination resulted in a predictable onset of sedation, with a mean induction time to lateral recumbency of 9.8 +/- 3.6 min. All deer recovered smoothly within a range of 5-20 min after reversal with intramuscular administration of naltrexone, atipamazole, and tolazoline (NAT). Clinically relevant decreases in arterial partial pressure of oxygen (PaO2) and oxygen saturation (SpO2) were observed in animals not receiving supplemental oxygen, while both parameters significantly improved for oxygen-supplemented deer. Pulse oximetry with this protocol was an unreliable indicator of oxygen saturation. In this study, altitude, recumbency, hypoventilation, butorphanol- and medetomidine-specific effects, as well as the potential for alpha 2 agonist-induced pulmonary changes all may have contributed to the development of hypoxemia. Overall, capture of white-tailed deer with the BAM/NAT protocol resulted in excellent chemical immobilization and reversal. Because the BAM combination caused significant hypoxemia that is unreliably detected by pulse oximetry but that may be resolved with nasal oxygen insufflation, routine use of oxygen supplementation is recommended.

Immobilization of Black Bears (Ursus americanus) with a Combination of Butorphanol, Azaperone, and Medetomidine

Sixteen captive and five free-ranging black bears (Ursus americanus) were immobilized with a combination of butorphanol, azaperone, and medetomidine (BAM). The BAM drug combination was premixed using 0.5 ml butorphanol (30 mg/ml), 0.25 ml azaperone (50 mg/ml), and 0.25 ml medetomidine (20 mg/ml) per milliliter to yield a final mix of (15 mg butorphanol+12.5 mg azaperone+5 mg medetomidine)/ml. This combination, dosed at 0.4 ml BAM/approximately 23 kg estimated body weight, provided a mean induction time of 10 min (95% confidence interval [CI]=2 min), consistent anesthesia without apparent adverse effects, and smooth recovery (mean=15 min, 95% CI=4 min) after antagonism with atipamezole (5 mg/mg medetomidine) alone or in combination with naltrexone (5 mg/mg butorphanol). Based on our initial observations, BAM appears to be a reversible and accessible drug combination for immobilizing black bears that merits further evaluation for field use.

Influence of the combination of butorphanol and detomidine within premedication on the preoperative sedations score, the intraoperative cardiovascular situation and the early recovery period in horses

Influence of the combination of butorphanol and detomidine within premedication on the preoperative sedations score, the intraoperative cardiovascular situation and the early recovery period in horses

EFFECTS OF SEDATION WITH MIDAZOLAM AND BUTORPHANOL ON RESISTIVE AND PULSATILITY INDICES IN HEALTHY DOGS

Resistive index (RI) and pulsatility index (PI) are indirect measurements of blood flow resistance that may be measured by pulsed wave Doppler ultrasonography. Chemical restrain may potentially alter the indices although it is required to perform ultrasonography in some patients. The purpose of this study was to describe values for both intrarenal and ocular RI and PI within the same subject in clinically normal dogs sedated with a midazolam and butorphanol combination and evaluate if there are any significant changes between sedated and nonsedated dogs. Fifteen healthy Beagle dogs were studied by Duplex Doppler interrogation in interlobar or arcuate arteries of the kidney and long posterior ciliary artery. Pulse rate and systolic blood pressure were also determined. All measurements were recorded before and after the administration of a sedative combination of midazolam (0.2 mg/kg) and butorphanol (0.2 mg/kg). Mean comparison tests (paired t-tests or Wilcoxon's rank-sum test) were used to determine if any significant differences existed between right and left renal values or right and left ocular values. A correlation study (Pearson or Spearman) was applied between RI, PI, and systolic pressure, and pulse rate. RI and PI were significantly higher in sedated Beagles than in unsedated Beagles. There was neither correlation between index and systolic blood pressure nor pulse rate. In conclusion, provided that normal RI and PI increase in sedated animals, then reference ranges should be higher when sedated--healthy or ill--animals are evaluated.

Clinical efficacy and safety of dexmedetomidine and buprenorphine, butorphanol or diazepam for canine hip radiography

To investigate the usefulness of dexmedetomidine for restraint and sedation during hip radiographic examination of hip-extended or stress-radiography views when combined with either buprenorphine, butorphanol or diazepam. One hundred and twenty-seven client-owned clinically healthy golden retrievers or rottweilers were enrolled in a clinical trial that compared hip-extended and PennHIP methods for diagnosing hip dysplasia and were randomly allocated to receive dexmedetomidine or medetomidine in combination with buprenorphine, butorphanol or diazepam. Subjective assessments were made for response to pain, response to noise, palpebral reflex, muscle tone and overall quality of sedation; non-invasive physiological variables were also recorded. Overall quality of sedation was graded as good or excellent for dogs administered with a combination of butorphanol or diazepam. However, more dogs that received a combination involving buprenorphine had overall a relatively poorer quality of sedation and required additional administration of buprenorphine before the radiographic procedure could commence. Once sedated, clinically sufficient muscle relaxation accompanied by a very low proportion of dogs responding to pain or noise stimuli were observed in all treatment groups. Heart and respiratory rate, and procedure and recovery times were similar for all treatment groups, and no adverse events were observed during the study. Dexmedetomidine sedative protocols, particularly in combination with butorphanol and diazepam, can be used effectively and safely in dogs for radiographic procedures.

Comparison of butorphanol and thiopentone vs fentanyl and thiopentone for laryngeal mask airway insertion

Study Objective To compare laryngeal mask airway (LMA) insertion conditions using a combination of butorphanol and thiopentone vs fentanyl and thiopentone. Design Prospective, randomized, and double-blind study. Setting Operating theater. Patients One hundred four females, with American Society of Anesthesiologists grades I and II, diagnosed with carcinoma cervix scheduled for intracavitary implant placement, were recruited into the study. The patients were randomly divided into 2 groups of 52 each. Intervention Anesthesia was induced with butorphanol (30 μg kg −1) and thiopentone in group B and fentanyl (1.5 μg kg −1) and thiopentone in group F, followed by LMA insertion. Anesthesia was maintained with O 2, N 2O, and isoflurane with spontaneous ventilation. Measurements Six variables were noted on a 3-point scale: jaw relaxation (nil/slight/gross), ease of insertion (easy/difficult/impossible), swallowing (nil/slight/gross), coughing/gagging (nil/slight/gross), limb/head movement (nil/slight/gross), and laryngospasm (nil/slight/gross). Postoperatively, sedation score was assessed on a 4-point scale at 1/2 hour, 1 hour, and 2 hours. Main Results The 2 groups were demographically similar. Incidence of full jaw relaxation at first attempt was significantly higher in group B vs F (48 vs 35 patients, P = 0.003). Insertion was easy in 48 vs 37 patients in group B and F, respectively ( P = 0.017). The incidence of swallowing, patient movements, and laryngospasm was comparable among the groups. Coughing/gagging was significantly lower in group B ( P = 0.008). Significantly more patients were sedated in group B at 1/2 hour ( P = 0.010) and 1 hour ( P = 0.000). None of the patients were deeply sedated at 1 hour. At 2 hours, all patients were awake. Conclusion The use of butorphanol and thiopentone as induction agents produced excellent LMA insertion conditions compared to fentanyl and thiopentone (98% vs 86% success rate with 92% vs 71% easy insertion).

This Month in Anesthesiology

This Month in Anesthesiology

Comparison of morphine and butorphanol as pre-anaesthetic agents in combination with romifidine for field castration in ponies

Objective The aim of this study was to compare two different α2 agonist–opioid combinations in ponies undergoing field castration.Study design Prospective double-blind randomized clinical trial.Animal population Fifty-four ponies undergoing field castration.Materials and methods The ponies were randomly allocated to receive one of three different pre-anaesthetic medications [intravenous (IV) romifidine 100 μg kg−1 and butorphanol 50 μg kg−1; romifidine 100 μg kg−1 and morphine 0.1 mg kg−1 IV, or romifidine 100 μg kg−1 and saline IV] before induction of anaesthesia with ketamine 2.2 mg kg−1 IV. Further doses of romifidine (25 μg kg−1) and ketamine (0.5 mg kg−1) were given when required to maintain anaesthesia. Quality of sedation, induction of anaesthesia, maintenance of anaesthesia, recovery, and surgical condition were assessed using a visual analogue scale scoring system and compared. The effects of the different drug combinations on heart and respiratory rate were evaluated and the recovery time was recorded.Results Anaesthesia was considered adequate for surgery in all ponies. No anaesthetic complications were observed. Quality of sedation was significantly better in the butorphanol group compared with the control group (p = 0.0428). Overall quality of anaesthesia was better in the butorphanol group compared with morphine (p = 0.0157) and control (p < 0.05) groups. Quality of induction of anaesthesia and recovery were not significantly different between groups, nor were the surgical conditions, recovery time and the number of repeated anaesthetic doses required during the procedure. Muscle twitches were observed in both the control and morphine groups. Maintenance of anaesthesia was judged to be smoother in the butorphanol group compared with the morphine and control groups (p = 0.006). Heart rate decreased significantly (p < 0.01) in all groups after administration of sedatives but did not differ significantly between groups at any time point.Conclusion The combination of butorphanol and romifidine was found to provide better sedation compared with the other drug combinations.Clinical relevance The combination of butorphanol and romifidine provided better sedation, but morphine was found to be a suitable alternative to butorphanol. Use of morphine and butorphanol in combination with α2 agonists should be further investigated to assess their analgesic effects.

Antinociceptive Effects of Hydromorphone, Butorphanol, or the Combination in Cats

The goal of this study was to assess the antinociceptive activity of a single dose of hydromorphone or butorphanol and to examine the effect of their coadministration on thermal thresholds in cats. Thermal thresholds were measured after IM administration of hydromorphone (0.1 mg/kg), butorphanol (0.4 mg/kg), a combination of butorphanol and hydromorphone (0.4 and 0.1 mg/kg), or saline to each of 6 cats in a randomized, blinded, crossover study design. There were at least 12 days between treatments. Thermal thresholds were measured by a thorax‐mounted thermal threshold‐testing device specifically developed for cats. Thermal thresholds were measured before treatment, at varying intervals to 12 hours, and at 24 hours after treatments. Data were analyzed by an analysis of variance with a repeat factor of time. Dysphoria was associated with butorphanol administration but not with hydromorphone or hydromorphone‐butorphanol combined administration. Vomiting was seen with hydromorphone but not with butorphanol or hydromorphone‐butorphanol combined. The control treatment group was stable over time(P=.22; mean threshold, 40.1oC). Thresholds were significantly(P&lt;05) higher than the control treatment between 15 and 165 minutes for butorphanol, between 15 and 345 minutes for hydromorphone, and between 15 and 540 minutes for hydromorphone‐butorphanol combined. The addition of butorphanol to hydromorphone decreased the intensity of antinociception during the 1st 2 hours but extended the duration of observable antinociception from 5.75 to 9 hours. The present study suggests that the combination of butorphanol and a pure OP3 (mu) receptor agonist clinically does not produce increased analgesia and indeed may result in decreased analgesia.

Antinociceptive effects of hydromorphone, butorphanol, or the combination in cats.

The goal of this study was to assess the antinociceptive activity of a single dose of hydromorphone or butorphanol and to examine the effect of their coadministration on thermal thresholds in cats. Thermal thresholds were measured after IM administration of hydromorphone (0.1 mg/kg), butorphanol (0.4 mg/kg), a combination of butorphanol and hydromorphone (0.4 and 0.1 mg/kg), or saline to each of 6 cats in a randomized, blinded, crossover study design. There were at least 12 days between treatments. Thermal thresholds were measured by a thorax-mounted thermal threshold-testing device specifically developed for cats. Thermal thresholds were measured before treatment, at varying intervals to 12 hours, and at 24 hours after treatments. Data were analyzed by an analysis of variance with a repeat factor of time. Dysphoria was associated with butorphanol administration but not with hydromorphone or hydromorphone-butorphanol combined administration. Vomiting was seen with hydromorphone but not with butorphanol or hydromorphone-butorphanol combined. The control treatment group was stable over time (P = .22; mean threshold, 40.1 degrees C). Thresholds were significantly (P < .05) higher than the control treatment between 15 and 165 minutes for butorphanol, between 15 and 345 minutes for hydromorphone, and between 15 and 540 minutes for hydromorphone-butorphanol combined. The addition of butorphanol to hydromorphone decreased the intensity of antinociception during the 1st 2 hours but extended the duration of observable antinociception from 5.75 to 9 hours. The present study suggests that the combination of butorphanol and a pure OP3 (mu) receptor agonist clinically does not produce increased analgesia and indeed may result in decreased analgesia.

Analgesic effect of pre-operative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy

The analgesic, bleeding, and renal effects of dogs pre-medicated with etodolac with and without butorphanol were evaluated. Twenty-four 1-year-old healthy dogs, weighing 19 ± 3 kg (mean ± SD) were randomly assigned to four treatment groups (n = 6): control (C), etodolac (E), butorphanol (B), and etodolac with butorphanol (EB). Etodolac (12–14 mg kg−1 PO) was given 1 hour before propofol induction and isoflurane maintenance anesthesia. Butorphanol (0.4 mg kg−1 IV) was given immediately following endotracheal intubation. Control dogs received only propofol (8 mg kg−1 to effect) and isoflurane anesthesia. All dogs were mechanically ventilated to maintain Pe′CO2 between 35 and 45 mm Hg (4.7–6.0 kPa). Lactated Ringer's solution was given at 10 mL kg−1 hour−1 during anesthesia. Plasma cortisol concentrations were assessed 1 day prior to surgery (baseline), immediately prior to anesthesia induction, and every 30 minutes until 5 hours following extubation, and 1 day after surgery. Total duration of anesthesia was 50 minutes and total surgery duration was 30 minutes. Isoflurane concentration area under the curve (AUC) over time during the anesthesia was compared among treatment groups. Buccal mucosal bleeding time (BMBT) was assessed 1 day before E administration and during surgery. Urine GGT to urine creatinine ratio, BUN, and plasma creatinine were taken daily from 1 day before to 3 days after surgery. Behavioral pain scores (numerical rating scale) were assessed by two observers blinded to the treatment during the 5-hour recovery period at 30 minute intervals until 3 hours, and again at 5 hours after extubation. All data were analyzed using anova. Multiple comparisons were performed if the anova was significant. Alpha value was set at 0.05. Plasma cortisol concentrations significantly increased from time of extubation in all the treatment groups. They did not return to the baseline until 5, 2.5, 1.5, and 1.5 hours after extubation in the C, B, E, and EB groups, respectively. Isoflurane AUC was not significantly different among treatment groups. Dogs treated with EB had significantly less behavioral pain than all other groups throughout the 5-hour recovery period. No significant difference was found between treatment groups or within treatment groups over time in BMBT, or any renal variables. This study demonstrated that (i) pre-operative administration of E provides profound analgesia during the post-operative period without renal or bleeding side-effects in dogs undergoing OHE; and (ii) a combination of butorphanol–etodolac provides the best analgesic effect during the post-operative period based on the behavioral pain score.

犬の全身吸入麻酔時における前投薬としてのドロペリドールーブトルファノールの効果

The effects of droperidol 0.25mg/kg IV without butorphanol (Group A, n=41) or combined with butorphanol 0.0125mg/kg (Group B, n=41), 0.025mg/kg (Group C, n=40), 0.05mg/kg (Group D, n=41), 0.1mg/kg (Group E, n=43), or 0.2mg/kg (Group F, n=41) N were evaluated as premedication before inhalation anesthesia in 247 dogs. Surgical anesthesia was induced by ketamine5mg/kg IV and maintained with 50% nitrous oxide-50% oxygen-sevoflurane. All dogs calmed down and relaxed and demonstrated moderate sedation after premedication. Butorphanol produced dose-dependent enhancement sedation. The end-tidal concentration of sevoflurane during surgery varied between 2.0 and 2.3% with no significant differences among groups. Body temperature during surgery was approximately 37.7°C in group A and 36.5 37.3°C in groups B, C, D, E, and F. Throughout surgery heart rate and partial pressure of end-tidal CO2 were maintained within normal limits for dogs (approximately 110-130 bpm and 30-40mmHg). Shallow breathing occurred during surgery in 5 dogs in Group A, 6 dogs in GroupB, 7 dogs in Group C, 9 dogs in Group D, 16 dogs in Group E, and 13 dogs in Group F. Hypotension occurred in 8 dogs in Group F. Recovery from anesthesia was rapid, and most dogs were extubated by 10 minutes after cessation of anesthesia. The combination of butorphanol enhances sedation. It did not, however, enhance analgesia sufficiently to reduce the sevoflurane concentration necessary to anesthesia maintenance. Combination with 0.1 0.2mg/kg of butorphanol may induce respiratory and circulatory depression during inhalation anesthesia. We therefore recommend combining 0.25mg/kg of droperidol with 0.0125-0.05mg/kg N as premedication for inhalation anesthesia in dogs.

Drug discrimination history: Pigeons trained to discriminate opioids with activity at different receptor types.

In pigeons (Columba livia; N = 5) trained to discriminate the mu (mu) opioid butorphanol from saline, various mu (morphine, fentanyl) but not kappa (kappa; bremazocine, U50,488, U69,593) opioids produced at least 80% drug-appropriate responding. Subsequently, pigeons were retrained to discriminate the kappa opioid bremazocine from saline; in this condition, both mu and kappa opioids produced at least 80% drug-appropriate responding, naloxone was more potent as an antagonist of the butorphanol stimulus, and chronic bremazocine treatment selectively produced tolerance to the bremazocine stimulus. Although butorphanol can function as a kappa antagonist, the effects produced by combinations of butorphanol and bremazocine during training with bremazocine were generally effect-additive. The findings indicate that the mechanisms underlying the stimulus effects of mu opioids are not altered by subsequent training with a kappa opioid. Conversely, a history of discrimination training with a mu opioid does not alter the discriminative control produced by kappa opioids during subsequent training with a kappa opioid.

Drug discrimination history: pigeons trained to discriminate opioids with activity at different receptor types.

In pigeons (Columba livia; N = 5) trained to discriminate the mu (mu) opioid butorphanol from saline, various mu (morphine, fentanyl) but not kappa (kappa; bremazocine, U50,488, U69,593) opioids produced at least 80% drug-appropriate responding. Subsequently, pigeons were retrained to discriminate the kappa opioid bremazocine from saline; in this condition, both mu and kappa opioids produced at least 80% drug-appropriate responding, naloxone was more potent as an antagonist of the butorphanol stimulus, and chronic bremazocine treatment selectively produced tolerance to the bremazocine stimulus. Although butorphanol can function as a kappa antagonist, the effects produced by combinations of butorphanol and bremazocine during training with bremazocine were generally effect-additive. The findings indicate that the mechanisms underlying the stimulus effects of mu opioids are not altered by subsequent training with a kappa opioid. Conversely, a history of discrimination training with a mu opioid does not alter the discriminative control produced by kappa opioids during subsequent training with a kappa opioid.

Butorphanol and Promethazine as Pre-anaesthetic Medication

An open evaluation of a combination of butorphanol (1 or 2 mg), promethazine (25 or 50 mg) and atropine (0.5 mg) in 109 adult consenting patients was carried out to determine their safety and efficacy for preanaesthetic medication. All patients were kept under direct surveillance from before intramuscular medication until they were in satisfactory condition post-operatively for discharge from the recovery room. The medications employed did not disturb the blood pressure, pulse rate or respiration rate in any of the patients. None complained of nausea or dizziness while only one was slightly excited. Sedation was rated as satisfactory in 97 per cent, and 90 per cent were free of apprehension. In addition, global evaluation of the premedication by the investigator was rated good to excellent in 99 per cent of the patients. On the basis of these observations, the combination of butorphanol with promethazine and atropine appears safe and useful for pre-anaesthetic medication.

Butorphanol and Promethazine as Pre-Anaesthetic Medication

An open evaluation of a combination of butorphanol (1 or 2 mg), promethazine (25 or 50 mg) and atropine (0.5 mg) in 109 adult consenting patients was carried out to determine their safety and efficacy for preanaesthetic medication. All patients were kept under direct surveillance from before intramuscular medication until they were in satisfactory condition post-operatively for discharge from the recovery room. The medications employed did not disturb the blood pressure, pulse rate or respiration rate in any of the patients. None complained of nausea or dizziness while only one was slightly excited. Sedation was rated as satisfactory in 97 per cent, and 90 per cent were free of apprehension. In addition, global evaluation of the premedication by the investigator was rated good to excellent in 99 per cent of the patients. On the basis of these observations, the combination of butorphanol with promethazine and atropine appears safe and useful for pre-anaesthetic medication.