Showing papers on "Buprenorphine published in 1990"

Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal.

Abstract: Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52, all subjects received placebo. Subjects receiving buprenorphine on alternate days reported significantly greater urge for an opioid, increased dysphoria scores, and pupillary dilation on placebo days. After abrupt termination of buprenorphine, no withdrawal signs were detected with the Himmelsbach scale. However, subjects reported mild-to-moderate opioid withdrawal symptoms, peaking at 3 to 5 and lasting for 8 to 10 days. Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between-dose interval of 48 hours.

Buprenorphine and naltrexone effects on cocaine self-administration by rhesus monkeys.

Abstract: The effects of daily treatment with buprenorphine (0.237-0.70 mg/kg/day), naltrexone (0.32-3.20 mg/kg/day) and saline on cocaine self-administration were compared in rhesus monkeys. Cocaine (0.05 or 0.10 mg/kg/injection) and food (1-g banana pellets) self-administration were maintained on a fixed-ratio 4 (variable ratio 16:S) schedule of reinforcement. Buprenorphine, naltrexone or an equal volume saline control solution were infused slowly over 1 hr through one lumen of a double lumen i.v. catheter at the same time each day. Saline and each dose of buprenorphine (0.237, 0.40 and 0.70 mg/kg/day) or naltrexone (0.32 and 3.20 mg/kg/day) were studied for 60 sessions over 15 consecutive days. Buprenorphine significantly suppressed cocaine self-administration (P less than .001-.0001) in comparison to saline in all monkeys. Cocaine self-administration decreased by 49 to 95% in five of six monkeys on the 1st day of buprenorphine administration (0.237 and 0.40 mg/kg/day) and remained suppressed by an average of 72 to 93% during buprenorphine treatment. After abrupt termination of buprenorphine treatment (0.237 and 0.70 mg/kg/day), cocaine self-administration remained suppressed for an average of 16 +/- 4.4 and 28 +/- 6.6 days, respectively. Buprenorphine (0.237 and 0.40 mg/kg/day) initially suppressed food self-administration in some monkeys (P less than .01), but tolerance developed to buprenorphine's effects on food-maintained responding whereas cocaine self-administration remained significantly suppressed. During treatment with 0.70 mg/kg/day of buprenorphine, food self-administration returned to or significantly exceeded (P less than .01) base-line levels in three animals. Daily patterns of food self-administration were not disrupted by buprenorphine treatment. Naltrexone (0.32 mg/kg/day) initially suppressed cocaine self-administration by an average of 28% over 15 days (P less than .0009). During high-dose naltrexone treatment (3.20 mg/kg/day), cocaine-maintained responding was suppressed by 25% over 15 days (P less than .01). Cocaine-maintained responding was not significantly changed by naltrexone in one of the five subjects. Food self-administration decreased by 24% (P less than .05) after 5 days of 0.32 mg/kg of naltrexone administration, then exceeded baseline levels during 3.20 mg/kg of naltrexone administration. These data suggest that buprenorphine decreases cocaine's reinforcing properties more effectively than naltrexone across the dose-range studied. Buprenorphine may be an effective pharmacotherapy for treatment of cocaine abuse as well as dual abuse of cocaine plus heroin.

Buprenorphine disposition in patients with renal impairment: single and continuous dosing, with special reference to metabolites

Abstract: The disposition of buprenorphine has been studied in two patient groups to assess the influence of impaired renal function on the metabolism of buprenorphine and two of its metabolites, buprenorphine-3-glucuronide (B3G) and norbuprenorphine (NorB). A single i.v. dose of 0.3 mg was given to 15 patients (nine with dialysis-dependent renal failure) undergoing lower abdominal or peripheral body surface surgery. Blood was sampled up to 24 h. Concentrations of buprenorphine, B3G and NorB were assayed by a differential radio-immunoassay technique. There were no differences in buprenorphine kinetics between anaesthetized healthy patients and those with renal impairment: mean elimination half-lives 398 and 239 min; clearance 651 and 988 ml min−1apparent volume of distribution at steady state 313 and 201 litre, respectively. Both metabolites were undetectable following the single i.v. dose. In a second group of 20 patients (eight with renal impairment), buprenorphine was administered by continuous infusion for provision of analgesia and control of ventilation in the ITU (median infusion rate 161 μg h−1 (range 36–230 μg h−1) for a median duration of 30 h (2–565 h). Buprenorphine clearance in patients with normal and impaired renal function was similar (934 and 1102 ml min−1, respectively), as were dose-corrected plasma concentrations of buprenorphine. In patients with renal failure, plasma concentrations of NorB were increased by a median of four times, and B3G concentrations by a median of 15 times.

Buprenorphine abuse: report from India

Abstract: av>c Buprenorphine has been stated a drug of low abuse potential and often used therapeutically in the management of opiate addicts. An analysis of 2 ^years' experience of opiate addiction cases at a de-addiction clinic revealed its increasing rate of abuse, especially as a substitute for heroin.

Intrathecal etorphine, fentanyl and buprenorphine on spinal nociceptive neurones in the rat

Abstract: Single unit recordings were made in the lumbar dorsal horn in the intact anaesthetized rat from convergent, multireceptive neurones. Activity was evoked by Aβ and C fibre transcutaneous electrical stimulation of hind paw receptive fields. Three opioids, fentanyl, etorphine and buprenorphine were applied either intrathecally or intravenously and their effects on neuronal responses were examined. Intrathecal fentanyl and etorphine produced clear selective naloxone-reversible inhibitions of C fibre-evoked responses (ED 50 = 24 μg and 0.6 μg respectively). Fentanyl, a μ opioid receptor agonist, was more potent at a given dose when given systemically, but etorphine, a non-selective opioid agonist, was similarly potent by both routes. In contrast to fentanyl and etorphine, intrathecal buprenorphine produced facilitations of C fibre-evoked responses at a low dose (15 μg), but inhibited both C and Aβ fibre-evoked responses equally at a higher dose (125 μg). Inhibitions were found to be irreversible by naloxone. No inhibition of either C or A/gb responses occurred following intravenous buprenorphine (10–1070 βg). The results are discussed in the light of the relationships between lipophilicity, opioid receptor selectivity and potency for spinally applied opioids.

Pharmacokinetics of morphine and its surrogates. X: Analyses and pharmacokinetics of buprenorphine in dogs.

Abstract: Specific and sensitive reverse-phase HPLC assays of buprenorphine and its metabolite in biological fluids were developed with sensitivities of 2-6 ng ml-1 using fluorimetric detection. Pharmacokinetics were monitored on acute bolus administration of buprenorphine in 6 dogs within the 0.7-2.6 mg kg-1 dose range. Toxicity was circumvented when terminal plasma concentrations were increased by infusing 3.7-4.8 mg kg-1 doses of buprenorphine over 3 h in six studies in 6 dogs. The terminal rate constants of the IV infusion studies from the triexponential fits of plasma concentration-time data averaged 41.6 +/- 7.5 h with an averaged total body clearance of 191 +/- 19 ml min-1. This terminal rate constant was in contrast to the less than 100 min half-life of the second exponential fitting of the less lipophilic morphine, naloxone, and naltrexone. The apparent volumes of distribution of buprenorphine, referenced to the total plasma concentration, were 33 +/- 61 (Vc, central compartment volume) and 663 +/- 891 (Vd, total body volume), indicative of a highly bound, sequestered or lipophilic drug. Unchanged buprenorphine was insignificantly renally (less than 0.2 per cent of the dose) and biliary (less than 0.6 per cent) excreted. The major route of buprenorphine disposition was by hepatic conjugation to glucuronide which was eliminated into the bile (about 92 per cent) with only small amounts appearing in urine (less than 1 per cent as metabolite). Minor metabolites excreted in the bile accounted for about 3 per cent of the administered dose. Direct IV administration of the metabolite, buprenorphine glucuronide, gave a terminal half-life of 6 h and more than 90 per cent of the systemically circulating metabolite was excreted in bile; only 10 per cent in urine. The oral bioavailability, estimated from the areas under the buprenorphine plasma concentration-time curve following IV and oral administration of buprenorphine in the dogs, was 3-6 per cent. There were no apparent correlations of the buprenorphine time course with cardiovascular parameters such as heart rate, ECG, and blood pressure. Miotic effect was significant. Respiratory depression was observed during the first 4 h after IV bolus injection, but not during the infusion studies.

Interactions between mu and kappa opioid agonists in the rat drug discrimination procedure.

Abstract: The present study was designed to explore the nature of the interaction between mu and kappa opioid agonists in the rat drug discrimination procedure. In rats trained to discriminate the kappa agonist U50,488 (5.6 mg/kg) from water, the other kappa agonist bremazocine substituted completely for the U50,488 training stimulus, and the additional kappa agonist tifluadom substituted in three of five of rats tested. In contrast, the mu agonists morphine, fentanyl, and buprenorphine produced primarily vehicle-appropriate responding. When morphine, fentanyl, and buprenorphine were combined with the training dose of U50,488, all three mu agonists reduced U50,488-appropriate responding. In rats trained to discriminate the mu agonist morphine (10.0 mg/kg) from saline, the other mu agonists morphine and buprenorphine all substituted in a dose-dependent manner for the morphine training stimulus, whereas U50,488, bremazocine, and tifluadom produced primarily vehicle-appropriate responding. When combined with the training dose of morphine, bremazocine antagonized morphine's discriminative stimulus effects, whereas U50,488 and tifluadom had no effect. The barbiturate pentobarbital neither substituted for, nor antagonized, the discriminative stimulus effects of either U50,488 or morphine. These results suggest that mu agonists and kappa agonists produce interacting effects in the drug discrimination procedure in rats.

Current pharmacotherapies for opioid dependence.

Abstract: Pharmacotherapy of intravenous opioid abusers has taken on increased urgency with the acquired immunodeficiency syndrome (AIDS) epidemic, because in major cities intravenous drug abuse now accounts for half of new AIDS cases. The pharmacotherapy of acute dependence and withdrawal has benefited from the use of clonidine, particularly in combination with antagonist-precipitated withdrawal. However, protracted abstinence and its associated risk of relapse to drug abuse has underscored the need for maintenance pharmacotherapies. Maintenance pharmacotherapies such as methadone and naltrexone are frequently needed to sustain outpatient retention and abstinence from heroin. Methadone is more widely used than is naltrexone, an oral, long acting heroin blocker that can maintain drug abstinence after detoxification. Because of limitations in both of these maintenance agents, two investigational maintenance treatments have been tested: levo-alpha-acetylmethadol (LAAM), a long-acting form of methadone, and buprenorphine, a long-acting mixed opioid agonist-antagonist with properties similar to either methadone or naltrexone, depending on dose. Clinical use, limitations, and outcome with each medication are reviewed.

Discriminative stimulus effects of opioid agonists in morphine-dependent pigeons

Abstract: Discriminative stimulus effects of opioid agonists were studied in morphine-dependent (10.0 mg/kg/day) pigeons discriminating among i.m. injections of morphine (10.0 mg/kg), saline and naltrexone (0.032 mg/kg) while responding under a fixed ratio schedule of food presentation. Morphine and naltrexone occasioned responding on the respective correct keys in a dose-related manner with complete generalization (greater than or equal to 90% correct) occurring with doses of morphine larger than 10.0 mg/kg and doses of naltrexone larger than 0.001 mg/kg. Several opioid mu and kappa agonists were studied in dependent pigeons and in morphine-abstinent pigeons (i.e., 30-hr morphine-deprived). The opioid mu agonist etonitazene substituted completely for morphine in dependent pigeons; in abstinent pigeons a small dose of etonitazine reversed withdrawal and larger doses substituted for morphine. Some opioid agonists did not substitute completely for morphine in dependent pigeons and partially (nalbuphine, meperidine) or completely (butorphanol, buprenorphine) reversed withdrawal in abstinent pigeons. In contrast, the opioid kappa agonists trans-3,4-dichloro-N-methyl-N(2-[1-pyrrolidinyl]cyclohexyl) benzeneacetamide methanesulfonate and bremazocine did not substitute for morphine or for naltrexone in dependent pigeons and did not reverse withdrawal in abstinent pigeons. Moreover, in dependent pigeons buprenorphine, butorphanol and nalbuphine, but not trans-3,4-dichloro-N-methyl-N(2-[1-pyrrolidinyl]cyclohexyl)benzeneace tam ide methanesulfonate, antagonized the discriminative stimulus effects of morphine and of naltrexone. These results confirm in morphine-dependent pigeons qualitative differences in discriminative stimulus effects among mu and kappa opioid agonists and support the notion that differences among agonists under some conditions can result from variations in efficacy.

Sublingual buprenorphine as postoperative analgesic: a double-blind comparison with pethidine.

Abstract: Buprenorphine and pethidine as postoperative analgesics were compared in 96 women having gynaecological operations by lower laparotomy. A fixed dose of the respective drug was given in a double-blind and double-dummy manner, initially intramuscularly and thereafter by sublingual buprenorphine (0.4 mg) or intramuscular pethidine (75 mg) at the request of the patient during the first 24 h postoperatively. Patients receiving buprenorphine had longer dose intervals and thus needed fewer doses. The analgesic effect, as assessed by a visual analog scale, was similar with both drugs. There were no significant differences between the groups regarding respiratory depression and nausea. It appears that sublingual buprenorphine is as effective and safe as intramuscular pethidine in the postoperative period.

Postoperative analgesia in children who have genito-urinary surgery. A comparison between caudal buprenorphine and bupivacaine.

Abstract: A study conducted on 40 children, aged 1-11 years, who had genito-urinary surgery compared the quality and duration of analgesia after caudal blocks in two groups of patients. Group 1 (n = 20) received caudal bupivacaine 0.25% and group 2 (n = 20) caudal buprenorphine 4 micrograms/kg; each received 0.5 ml/kg body weight. Patients were operated on under general anaesthesia. Postoperative behaviour and severity of pain were measured on a 3-point scale. The results indicate that caudal buprenorphine provides excellent postoperative analgesia in children comparable to caudal bupivacaine in the early postoperative period. Buprenorphine proved better in the late postoperative period. Analgesia lasted from 20 hours to more than 24 hours after caudal buprenorphine with fewer side effects.

Subarachnoid buprenorphine administered by implantable micropumps.

Abstract: This report concerns 23 patients, the majority of whom are suffering from low back and chest pain caused by chest, urological or gynaecological cancer. These patients were treated with subarachnoid buprenorphine, administered in a single bolus or by slow infusion from micropumps, at a daily dose adapted to patients need (0.06-0.15 mg). The painful symptomatology was successfully controlled in all the cases treated, allowing the patients to live a virtually normal life. In no cases was respiratory depression or tolerance observed.

A transdermal delivery system for treatment of cocaine and heroin addiction

Abstract: For the treatment of cocaine and heroin addiction in a human or animal subject, there is disclosed a transdermal delivery system which includes as the active ingredient buprenorphine or a pharmaceutically-acceptable salt.

A Comparison of the Incidence of Pruritus Following Epidural Opioid Administration in the Parturient

Abstract: Epidural morphine is associated with a high incidence of pruritus when used for pain control in the post-Caesarean section population. The purpose of this study was to compare the incidence of pruritus associated with epidural morphine, fentanyl, buprenorphine and butorphanol. Sixty healthy Caesarean section patients were studied in a double-blind randomized fashion. Patients were questioned at 1, 3, 12 and 24 hours postpartum for the incidence of pruritus. This study demonstrated that the incidence of pruritus was significantly higher following the use of epidural morphine and fentanyl. Even though epidural butorphanol and buprenorphine exhibited a low incidence of pruritus, their duration of analgesia was not long enough to make either attractive for single-dose administration.

Total intravenous anaesthesia with propofol and buprenorphine

Abstract: Summary A combination of propofol infusion and two bolus doses of buprenorphine, 2.5 or 5.0 μg/kg were evaluated in a total intravenous anaesthesia technique in 36 patients of ASA grade 1 or 2 undergoing cholecystectomy. Additional boluses of propofol were given intravenously if needed. Systolic blood pressure after tracheal intubation increased significantly only in those who received the smaller dose of buprenorphine. Patients in both groups remained haemodynamically stable throughout surgery with minimal side effects. Recovery was fast even with prolonged infusions and without major side effects. No patient reported awareness on postoperative questioning.

Buprenorphine abuse : a case report.

Abstract: Search for a safe and effective analgesic is long and elusive. Buprenorphine was marketed as a potent and non-addictive narcotic drug. In recent years there have been various case reports highlighting its abuse potential. As the drug will be used more widely and particularly with its use in the detoxification of heroin dependence there is an eminent possibility of its abuse at larger scale in future. Physicians should be careful in its prescription and cases of its abuse should be actively sought tor. A case report along with literature review is presented here.

Postoperative pain treated with piroxicam and buprenorphine, each drug alone or in a combination

Abstract: AIM OF IIJvEsI?c;ATON: To study the analgetic effect and side effect profile of a combination of piroxicam (P) and buprenorphine (B) compared to a basic treatment with each drug separately on postoperative pain. MEZXIW: 80 patients of both sexes underwent total hip joint replacement in neurolept anesthesia. The study was performed during the first postoperative 48 hours as a randomized double blind three armed parallel group comparison. Group I recieved P (40 mg im t 40 mg orally within the study period) + B (0,3 mg im + 2,4 mg orally); group II recieved placebo (0) + B (as above); group III was treated with P (as above) t o. All groups had supplementary B on request as escape drug. Pain was measured 6 times using VAS. The number of supplementary B, side effects and postoperative blood loss was registered. RESOL’IS: VAS mean scores was in group I 11 nm-~ (g-221, in II 26 mm (13-44) and in III 26 mm (20-32) (P. 0,5%). The mean for supplementary B (0,2 mg sublinguals) requested was in group I 2 (2-5), in II 5 (o-9) and in III 6 (3-6) (P=2,7%). As group I and II recieved a basic treatment with 12 sublinguals, the number of total B consumption was 14, 17 and 6 respectively (P

Effects of morphine, buprenorphine, pentazocine and nalorphine on acquisition and extinction of active avoidance responses in rats

Abstract: The effects of subcutaneous administration of morphine, buprenorphine, pentazocine and nalorphine were studied at two dose levels in rats (low dose x 10 and high dose x 20 of equivalent human dose) on the performance of active avoidance responses using a shuttle box. Pretraining injections of both doses of pentazocine and low dose nalorphine impaired acquisition on day 1 and day 2. Morphine and buprenorphine (at both dose levels) and high dose nalorphine did not affect the acquisition process. Post-training administration of morphine (high dose) and buprenorphine (both doses) delayed extinction of active avoidance responses. Low dose of morphine, high dose of pentazocine and both doses of nalorphine did not appreciably affect the extinction process. Mu opioid receptor agonists probably act as reinforcers to facilitate memory.