Effect of butorphanol tartrate on shock-related discomfort during internal atrial defibrillation.
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BACKGROUND: In patients with atrial fibrillation, intracardiac atrial defibrillation causes discomfort. An easily applicable, short-acting analgesic and anxiolytic drug would increase acceptability of this new treatment mode. METHODS AND RESULTS: In a double-blind, placebo-controlled manner, the effect of intranasal butorphanol, an opioid, was evaluated in 47 patients with the use of a step-up internal atrial defibrillation protocol (stage I). On request, additional butorphanol was administered and the step-up protocol continued (stage II). Thereafter, if necessary, patients were intravenously sedated (stage III). After each shock, the McGill Pain Questionnaire was used to obtain a sensory (S), affective (A), evaluative (E), and total (T) pain rating index (PRI) and a visual analogue scale analyzing pain (VAS-P) and fear (VAS-F). For every patient, the slope of each pain or fear parameter against the shock number was calculated and individual slopes were averaged for the placebo and butorphanol group. All patients were cardioverted at a mean threshold of 4.4+/-3.3 J. Comparing both patient groups for stage II, the mean slopes for PRI-T (P=0.0099), PRI-S (P=0.019), and PRI-E (P=0.015) became significantly lower in the butorphanol group than in the placebo group. Comparing patients who received the same shock intensity ending stage I and going to stage II, in those patients randomized to placebo the mean VAS-P (P=0.023), PRI-T (P=0. 029), PRI-S (P=0.030), and PRI-E (P=0.023) became significantly lower after butorphanol administration. CONCLUSIONS: During a step-up internal atrial defibrillation protocol, intranasal butorphanol decreased or stabilized the value of several pain variables and did not affect fear. Of the 3 qualitative components of pain, only the affective component was not influenced by butorphanol. The PRI evaluated pain more accurately than the VAS. (+info)
Assessment of opioid partial agonist activity with a three-choice hydromorphone dose-discrimination procedure.
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The discriminative stimulus and subjective effects of opioid mixed agonist-antagonists were assessed in volunteer nondependent heroin users trained in a three-choice drug discrimination procedure to discriminate among the effects of i.m. administration of 2 ml of saline, 1 mg of hydromorphone, and 4 mg of hydromorphone (a morphine-like mu agonist). Other subjective, behavioral, and physiological measures were concurrently collected. The discrimination was readily learned by six of the eight subjects. After training, generalization curves were determined for the following i.m. drug conditions: hydromorphone (0.375-4.0 mg), pentazocine (7.5-60 mg), butorphanol (0.75-6 mg), nalbuphine (3-24 mg), and buprenorphine (0.075-0.6 mg). All five of the test drugs were discriminated significantly or showed trends toward being discriminated as hydromorphone 1 mg-like at one or more dose levels. Hydromorphone showed an inverted U-shaped dose-effect function on the hydromorphone 1 mg-like discrimination. Subjective effect measures produced clearer differentiation among the test drugs than did drug discrimination performance. The present results differ from those of a previous study that observed a close relationship between the results of the discrimination measure and subjective effect measures. The previous study used similar methods and test drugs but different training drugs (e.g., 3 mg of hydromorphone versus 6 mg of butorphanol versus saline). It appears that both the sensitivity of drug discrimination performance to between-drug differences and the relationship between discriminative and subjective effects depends upon the specific discrimination that is trained (e.g., two-choice or three-choice). The present high dose-low dose-saline discrimination procedure appears useful for assessing partial agonist activity. The present data are consistent with partial agonist activity for pentazocine, butorphanol, nalbuphine, and buprenorphine. (+info)
kappa-Opioid receptor effects of butorphanol in rhesus monkeys.
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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. (+info)
Butorphanol tartrate acts to decrease sow activity, which could lead to reduced pig crushing.
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The objective of this study was to determine whether administration of an analgesic to sows immediately after farrowing would allow them to lie more restfully. Sows lying on their pigs, causing them to be "crushed," is a major cause of pig mortality. Most deaths due to crushing occur during the first 3 d postpartum. For modern, lean-type sows, farrowing crates are relatively hard and unforgiving, even though they may be equipped with plastic-coated, expanded metal flooring. Indeed, many sows develop pressure sores on their shoulders, and this may contribute to the sows' discomfort. These sores may cause a sow to change position frequently to alleviate pain, thus increasing its chances of crushing pigs. Sixteen production sows were assigned to either a control group (C, n = 8) with litter size 11.71+/-.78 or an experimental group (B, n = 8) with litter size 11.63+/-1.22. Pigs born to C and B sows weighed 1.60+/-.04 and 1.37+/-.04 kg, respectively. The C sows were given no treatment, whereas the B sows were administered an i.m. injection of butorphanol tartrate at a dose of .15 mg/kg BW every 6 h until 3 d after farrowing. Data were collected on all sows using time-lapse photography (1 frame/.4 s) for a 3-d duration upon the initiation of farrowing. To assess the degree of comfort of each sow, body position changes were recorded when sows switched between lying, sitting, and standing. Data were analyzed by 12-h periods using Wilcoxon-Mann-Whitney equations. During the 72-h period, B sows tended to perform fewer position changes than C sows (P = .10). Specifically, position changes were fewer for B sows from 48 to 72 h postpartum (P<.06). There were no differences in position changes between treatments from 0 to 48 h postpartum (P>.50). There was no difference in the rate of crushing between treatments (C = 5, B = 5). The butorphanol did not seem to affect pig activity or normal behaviors or to create adverse effects, such as diarrhea. Although the sows given butorphanol showed a reduced number of position changes, the dose was intermediate, and a higher dose may have a greater effect. If pig mortality can be decreased, an analgesic protocol that is simple to administer and readily available to producers can be developed. Alternatively, using of more pliable flooring or an increase in sow body fat may allow sows to lie more stationary. (+info)
The effect of opioid and acepromazine premedication on the anesthetic induction dose of propofol in cats.
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The median effective dosage (ED50) for induction of anesthesia with propofol was determined by using the up-and-down method in 31 unpremedicated cats, in 30 cats premedicated with butorphanol, 0.4 mg/kg body weight (BW), and acepromazine, 0.1 mg/kg BW, intramuscularly, and in 30 cats premedicated with morphine, 0.2 mg/kg BW, and acepromazine, 0.1 mg/kg BW, intramuscularly. The dose required for a satisfactory anesthetic induction in 50% of unpremedicated cats (ED50) was 7.22 mg/kg BW and of premedicated cats was 5.00 mg/kg BW. The reduction in dose was statistically significant in both premedicated groups compared with no premedication. There was no significant difference in ED50 between premedication regimes. Cyanosis was the most common adverse effect observed in all groups following anesthetic induction with propofol. (+info)
Preemptive effects of a combination of preoperative diclofenac, butorphanol, and lidocaine on postoperative pain management following orthognathic surgery.
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The aim of the study was to investigate whether preemptive multimodal analgesia (diclofenac, butorphanol, and lidocaine) was obtained during sagittal split ramus osteotomy (SSRO). Following institutional approval and informed consent, 82 healthy patients (ASA-I) undergoing SSRO were randomly assigned to 1 of 2 groups, the preemptive multimodal analgesia group (group P, n = 41) and the control group (group C, n = 41). This study was conducted in a double-blind manner. Patients in group P received 50 mg rectal diclofenac sodium, 10 micrograms/kg intravenous 0.1% butorphanol tartrate, and 1% lidocaine solution containing 10 micrograms/mL epinephrine for regional anesthesia and for bilateral inferior alveolar nerve blocks before the start of surgery. Postoperative pain intensity at rest (POPI) was assessed on a numerical rating score (NRS) in the postanesthesia care unit (PACU) and on a visual analogue scale (VAS) at the first water intake (FWI) and at 24, 48, and 72 hours after extubation. POPI in the PACU was significantly lower in group P than in group C, whereas there were no significant differences at FWI, 24, 48, and 72 hours after extubation in both groups. Preemptive multimodal analgesia was not observed in this study. (+info)
Role of opioid receptors in neurogenic dural vasodilation and sensitization of trigeminal neurones in anaesthetized rats.
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Migraine headache is thought to be caused by a distension of meningeal blood vessels, the activation of trigeminal sensory neurones and the the development of a central sensitization within the trigeminal nucleus caudalis (TNC). It has been proposed that clinically effective 5-HT(1B/1D) agonists act peripherally to inhibit the release of calcitonin gene-related peptide (CGRP) and neurogenic dural vasodilation, and to attenuate nociceptive neurotransmission within the TNC. Since opioids are also effective anti-migraine agents the present studies investigated the role of opioids within the trigemino-vascular system in anaesthetised rats. Electrical stimulation of the dura mater evoked neurogenic dural vasodilation which was significantly inhibited by morphine (1 mg kg(-1)) the selective mu-opioid agonist DAGO (10 microg kg(-1)) and the mixed agonist/antagonist butorphanol (1 mg kg(-1)) but not by the kappa- and delta-opioid agonists (+/-) U50488H (100 microg kg(-1)) and DPDPE (1 mg kg(-1)). Morphine had no effect on CGRP-evoked dural vasodilation. In electrophysiological studies morphine (1 - 10 mg kg(-1)) significantly attenuated brainstem neuronal activity in response to electrical stimulation of the dura by 65% at 10 mg kg(-1). Morphine (3 mg kg(-1)) also inhibited the TNC neuronal sensitization following CGRP-evoked dilation. The present studies have demonstrated that opioids block the nociceptive neurotransmission within the trigeminal nucleus caudalis and in addition inhibit neurogenic dural vasodilation via an action on mu-opioid receptors located on trigeminal sensory fibres innervating dural blood vessels. These peripheral and central actions are similar to those of the 'triptan' 5-HT(1B/1D) agonists and could account for the anti-migraine actions of opioids. (+info)
Enadoline and butorphanol: evaluation of kappa-agonists on cocaine pharmacodynamics and cocaine self-administration in humans.
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Preclinical studies have demonstrated that kappa-opioid agonists can attenuate the neurochemical and behavioral effects of cocaine that are related to its reinforcing efficacy, suggesting that kappa-agonists may serve as pharmacotherapies for cocaine dependence. This 8-week inpatient study examined the ability of enadoline, a selective and high-efficacy kappa-agonist, and butorphanol, a mixed agonist with intermediate efficacy at both mu- and kappa-receptors, to reduce the direct pharmacodynamic effects and self-administration of intravenous cocaine in humans (n = 8). Acute doses of intramuscular enadoline (20, 40, and 80 microg/kg), butorphanol (1.5, 3, and 6 mg/70 kg) and placebo were examined separately as pretreatments during each of three test sessions with cocaine in a constrained random order. A cocaine dose-effect session (0, 20, and 40 mg cocaine i.v., 1 h apart) examined direct pharmacodynamic interactions on subjective and physiological indices; self-administration sessions examined choice behavior for cocaine (40 mg i.v. for six trials) versus money 1) in the presence of a sample cocaine dose with money choices presented in ascending value, and 2) in the absence of a sample dose with money choices presented in descending values. Enadoline (80 microg/70 kg) significantly (p < 0.05) reduced some of the positive subjective effects of cocaine (e.g., ratings of "high"), while butorphanol failed to modify subjective responses. Both agents were safely tolerated in combination with cocaine without adverse physiological responses. Cocaine self-administration was significantly greater across all pretreatment conditions when the sample dose was given and ascending money choices were used. Enadoline and butorphanol failed to modify cocaine self-administration. These data suggest that these kappa-agonists may be safely administered in the presence of cocaine but do not produce significant attenuation of cocaine's direct effects or self-administration under these acute dosing conditions. (+info)