Showing papers on "Buprenorphine published in 1987"

Investigation of the antinociceptive activity of buprenorphine in sheep.

Abstract: 1. Buprenorphine given intravenously (6 micrograms kg-1) was examined for its antinociceptive activity in unrestrained sheep using devices to measure thermal and mechanical thresholds. 2. The plasma levels of buprenorphine following intravenous injection over the time period of the antinociceptive testing were measured using a radioimmunoassay. 3. Buprenorphine produced a clear antinociceptive effect lasting for up to three and a half hours when measured by the thermal threshold test, but no detectable antinociception in the mechanical test. 4. The plasma levels of buprenorphine indicated that the drug was rapidly distributed in a manner not dissimilar to that reported in man, although individual animals showed a wide variation in some parameters. 5. When plasma levels of the drug were high (less than 700 pg ml-1) during the first sixty minutes, no antinociceptive activity in the thermal test could be detected, which may be due to the slow receptor kinetics shown by this drug.

Antipsychotic effect of buprenorphine in schizophrenia.

Abstract: The antipsychotic potency of the partial opiate agonist buprenorphine was evaluated in 10 neuroleptic-free schizophrenic patients suffering from frequent hallucinations, delusions, and severe formal thought disorders. Buprenorphine had a pronounced antipsychotic effect, which lasted about 4 hours, in patients with schizophreniform disorders (N = 4) and paranoid schizophrenia (N = 3).

Which potent opioid? Important criteria for selection.

Abstract: Opioids remain the drugs of choice for the treatment of severe pain. In recent years several new potent opioids have become available for clinical use. These newer drugs are generally safer than the older morphine-like compounds and their differing pharmacological and pharmacokinetic properties allow the physician to choose an appropriate drug according to the clinical situation and need of an individual patient. These drugs are classified according to their activity at the opioid receptors. The opioid agonists produce their pharmacological effect by an almost exclusive action at µ-receptors. The agonist-antagonist group are κ-receptor agonists and either competitive antagonists at the µ-receptor or weak μ-agonists.

Opioid pharmacokinetics in relation to their effects.

Abstract: The chemical structure of drug molecules determines their fundamental pharmacological properties by 'fit' to the receptor, but the physicochemical properties, particularly lipid solubility and fraction un-ionised, dominate in determining distribution in the body and the rate of access to the biophase containing the drug receptors. For example, fentanyl appears much more potent than morphine because similar effective biophase concentrations are achieved with much smaller doses. Pharmacokinetic and pharmacodynamic investigations of the relationships between dose and the time-courses of blood concentrations and pharmacological effects of opioid drugs have helped explain the commonly observed variability between patients and have been useful in deriving effective dosage regimens of opioids such as pethidine, morphine, fentanyl and methadone where blood concentrations are a determinant of pharmacological response and 'target' analgetic blood opioid concentrations have been identifiable. However, there are instances when blood opioid concentrations are not determinants of the analgetic response. Examples include opioids, such as buprenorphine, for which the drug-receptor dissociation rate determines the duration of action, heroin which first has to be metabolised to become an agonist, pentazocine which is an agonist at some opioid receptors and an antagonist at others, and opioids placed intra-spinally acting on receptors in the spinal cord.

Constant i.v. infusions of nalbuphine or buprenorphine for pain after abdominal surgery

Abstract: A double-blind, sex-stratified, study compared the analgesic efficacy and side effects of nalbuphine 10 mg ml-1 (group N) and buprenorphine 0.15mg mt-1 (group B) administered as a continuous infusion (0.2 ml kg-1/24 h), after abdominal surgery. Patients could request additional i.m. analgesic for pain. The study groups were well matched. The trial was stopped after 55 patients had been studied (nalbuphine 29, buprenorphine 26), because nine patients in the nalbuphine group had inadequate pain relief (P

Urodynamic studies after intrathecal fentanyl and buprenorphine in the dog

Abstract: Cystometrograms (CMG) and urethral pressure profiles (UPP) were used in six anesthetized dogs to study the urodynamic effects of intrathecal (IT) injections of fentanyl and buprenorphine. The CMG and UPP were examined for each of the two drugs in all dogs (four experiments per animal). The measurements were performed before and 15, 30, 60, 90, and 120 min after IT injection of either 1.5 micrograms/kg fentanyl or 2 micrograms/kg buprenorphine. Fifteen minutes after IT injection of fentanyl, reduction in bladder tone was already noted, followed by decreases in mean peak vesical pressure of 48.3% +/- 6.0 (SE) (P less than 0.05) and mean peak urethral pressure of 38% +/- 3.0 (P less than 0.05) between 30 and 60 min after injection. These decreases, occurring in each experiment, gradually lessened at 90 and 120 min. The effects of IT buprenorphine, a partial opioid agonist, on bladder and urethral dynamics were inconsistent and non-significant in all studies. Disturbances of micturition observed clinically after spinal opioid administration may be related to the decrease in intravesical pressure and the resulting highly compliant bladder. Relaxation of the urethral musculature seen 15 min after IT fentanyl may prevent overdistension of the bladder and its associated complications.

Prolonged and biphasic respiratory depression following epidural buprenorphine

Abstract: Ventilatory sensitivity to carbon dioxide was measured in six healthy volunteers before, and at various times up to 20 hours after, administration of epidural buprenorphine 0.15 mg with a modified Read rebreathing technique. The carbon dioxide response curves were depressed in a time-dependent, prolonged and biphasic manner. Significant depression was seen in the intercept values at an end tidal carbon dioxide of 7.2 kPa, for mouth occlusion pressure (p less than 0.01), tidal volume (p less than 0.05) and minute ventilation (p less than 0.05). A significant reduction of slope was obtained only for minute ventilation. Linear regression of respiratory rate changes during carbon dioxide stimulation, did not reach statistical significance. In conclusion, these data indicate that epidural buprenorphine, despite a high lipid solubility, causes respiratory depression to the same extent as epidural morphine. Surveillance of patients who receive epidural buprenorphine for postoperative pain relief is necessary.

Buprenorphine vs. morphine via the epidural route: a controlled comparative clinical study of respiratory effects and analgesic activity.

Abstract: Twelve patients with intense or very intense pain of the non-incident type, secondary to neoplasia, were divided at random into two groups and treated with an epidural dose of 3 mg of morphine in 10 ml of glucose solution (6 patients = group M) or with 0.3 mg of buprenorphine in the same vehicle (6 patients = group B). None of the patients had previously been treated with opioids by any route. After first determining basal values, the following assessments were carried out: (1) evaluation of the analgesic effect of the drugs with checks at 30 min and at 1, 2, 3, 4, 6 and 18 h after administration, using a visual analogue scale, a numerical rating scale and a simple descriptive scale; and (2) evaluation of effects on respiration by means of checks at 30 and 90 min and at 6 and 18 h, on control of breathing indices (P0.1; VE; VA; Ti/Ttot; VT/Ti; RR), gas exchange indices (delta(A-a)O2; VD/VT; pAO2; R) and blood gas and acid-base indices (paO2; paCO2; pH; HCO3-). The data obtained were analyzed statistically using analysis of variance and Student's t test. The study results showed very similar analgesic efficacy for both treatments at a single dosage level of morphine (3 mg) compared to buprenorphine (0.3 mg), which was approximately 3 times greater than an equivalent parenteral dose of morphine (10 mg). Analysis of the results revealed statistically, though not clinically, significant changes in respiratory function indices, only in the buprenorphine-treated group. The effects of buprenorphine on respiratory function, when administered epidurally at the above dosage, are less favourable than those of morphine in the early measurements, probably because of its greater systemic absorption; nevertheless, the risk of delayed respiratory depression appears to be less after buprenorphine than after morphine.

Developmental responses to opioids reveals a lack of effect on stress-induced corticosterone levels in neonatal rats

Abstract: 1 The neonate has an unusual capacity for survival and the possibility exists that mechanisms for controlling stress responses may differ in the developing animal. In adults both endogenous and exogenous opioids can modulate the corticosterone responses to stress. We have studied this effect in neonatal rats and found that opioid modulation is absent in early postnatal development. 2 Neonatal rats of either sex were injected with morphine (5–50 mg kg−1), fentanyl (10–100 μg kg−1), buprenorphine (0.1 − 30 mg kg−1) or naloxone (0.1 − 10 mg kg−1) and plasma corticosterone measured fluorimetrically 15 or 20 min later. In addition naloxone reversibility studies (1 mg kg−1, co-administered) were carried out for the opioid agonists. 3 In adult rats, elevations in plasma corticosterone caused by injection stress were potentiated by morphine, fentanyl and buprenorphine. In neonates, though injection stress-induced rises in plasma corticosterone were absent at 10 days, elevations were observed at 21 days and later. However, significant potentiation of this corticosterone response by fentanyl was absent at 21 days and at later ages (30 and 40 days) for morphine and buprenorphine. The potentiating effect of all three agonists did not become fully effective until day 45. In addition, in animals acclimatized to injection stress by 7 day injection pretreatment, fentanyl did not significantly alter corticosterone levels in 30 day old neonates. 4 High doses of naloxone (10 mg kg−1) significantly increased the corticosterone response to injection stress in adult rats but this effect was absent in 30 day old animals. A dose of naloxone (1 mg kg−1) which had no significant effect on the corticosterone response inhibited the effects of morphine, fentanyl and buprenorphine in 45 day old and adult rats. 5 This late development of opioid action is unusual in comparison with the maturation of endogenous peptides, receptors and antinociceptive responses and suggests that alternative mechanisms may be involved in stress-control in the neonate.

Epidural sufentanil versus intramuscular buprenorphine for postoperative analgesia. A double-blind comparative trial.

Abstract: Summary Epidural sufentanil 50 μg was compared with intramuscular buprenorphine 0.3 mg for postoperative pain relief. Patients were assigned randomly to one of two treatment groups and received both an intramuscular and epidural injection, one of which was a placebo. Onset of pain relief was faster and quality of analgesia superior during the first 2 hours in the patients who received epidural sufentanil but the duration of analgesia was longer in the buprenorphine group. Cardiovascular variables remained stable in all patients and no respiratory depression was observed. Side effects were more frequent following buprenorphine.

Continuous-plus-on-demand epidural infusion of buprenorphine versus morphine in postoperative treatment of pain. Postoperative epidural infusion of buprenorphine.

Abstract: In a randomized, double-blind study, buprenorphine was compared with morphine in the treatment of pain after major abdominal operations by means of continuous-plus-on-demand epidural infusion for constant analgesia. The patients received bolus epidural injections of 0.15 mg buprenorphine or 2 mg morphine-HCl prior to an on-demand epidural infusion of 0.03% buprenorphine or 0.25% morphine HCl at a basal rate of 0.06 ml/h. Over 50 h, mean buprenorphine consumption was 0.85 +/- 0.08 mg, and mean morphine consumption was 6.4 +/- 0.5 mg. Under the treatment, no discomfort or side-effects necessitating treatment occurred. We conclude that buprenorphine is a useful substitute for morphine in the treatment of pain after major abdominal operations by continuous-plus-on-demand epidural infusion, and that the relative analgesic potency ratio of epidural buprenorphine is 8.

[O.15 mg Intrathecal buprenorphine applied for postoperative analgesia. A clinical double-blind study].

Abstract: In a double-blind, randomized study of 29 patients who underwent orthopedic procedures we studied the additional effect of intrathecal buprenorphine on isobaricpinal anesthesia and postoperative analgesia. The injections were 20 mg tetracaine (19 patients) or 20 mg tetracaine plus 0.15 mg buprenorphine (10 patients). In both groups the drugs were contained within a total volume of 4 ml cerebrospinal fluid. Progression and regression of the sensory blockade of spinal anesthesia were estimated with pinprick; the motor blockade was judged by the Bromage scheme. Postoperative pain was evaluated by the patients using an analogue scale after Scott and Huskisson. Arterial blood gases, respiratory rate, blood pressure, and heart rate were measured and other side-effects determined. Both groups were comparable in age, body weight, height and duration of operation (Table 1). The addition of buprenorphine elevated the sensory blockade by three segments both during spread and regression of anesthesia (Figs. 1, 2). Postoperative analgesia was better up to 8 h after injection (p less than 0.05), after 8 h pain levels were equal in test and control groups (Fig. 3). After buprenorphine patients became aware of pain sensation 13 h after injection; in the control group the pain-free interval lasted only 9 h (p greater than 0.05). There were no differences in the need for postoperative analgesics between both groups. The respiratory rate was lower during the whole period of observation (p less than 0.05). The mean values for PaCO2, pH and BE were similar in both groups (Fig. 4). PaO2 was elevated in the buprenorphine group. There was no essential alteration of blood pressure after buprenorphine. The pulse rate, however, was slightly diminished.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind comparison of the relative efficacy, side effects and cost of buprenorphine and morphine in patients after cardiac surgery

Abstract: The analgesic efficacy, side effects and cost of administration of regimens of intravenous buprenorphine and intravenous morphine were compared in a randomized double-blind trial performed during the first 24 h after cardiac surgery. Seven patients received buprenorphine by intermittent intravenous injection and six received morphine by continuous infusion. Both these regimens provided good analgesia for the entire 24 h period, with only mild pain at rest and moderate pain on vigorous coughing. Both regimens also produced mild respiratory depression but this was not of clinical importance: the mean arterial PCO2 in both groups was less than 45 mmHg after extubation. The major difference between drugs in the clinical setting was the ease of administration. Buprenorphine had no narcotic code restriction and could be given by intermittent intravenous injection, whereas morphine required checking and handling as a restricted drug and administration by continuous intravenous infusion. When labour and material costs were computed, over the first 24 postoperative hours, it cost $19.76 per patient to administer morphine, but only $3.16 to administer buprenorphine. Thus the use of buprenorphine injections for the first 24 h after cardiac surgery produced pain relief and respiratory depression comparable to that produced by a morphine infusion, but with a significant cost saving in terms of labour and materials.

Buprenorphine as premedication and as analgesic during and after light isoflurane-N2O-O2 anaesthesia. A comparison with oxycodone plus fentanyl.

Abstract: Sixty patients undergoing gynaecological laparotomies under isoflurane anaesthesia received 0.4 mg of buprenorphine sublingually or 0.12 mg/kg of oxycodone intramuscularly in random order for preanaesthetic medication. Patients premedicated with buprenorphine were given buprenorphine before, during and after anaesthesia and patients premedicated with oxycodone received fentanyl before and during anaesthesia and oxycodone after anaesthesia. Buprenorphine premedication produced less drowsiness and sedation and alleviated patients' apprehension significantly (P less than 0.05) less than oxycodone. Systolic and diastolic blood pressure and heart rate were significantly (P less than 0.05 to P less than 0.01) higher after intubation in the buprenorphine group when compared with the oxycodone plus fentanyl group. After anaesthesia, spontaneous respiration started rapidly; the return of consciousness and immediate recovery occurred at the same rate in both groups. In the recovery room moderate to severe pain was more common (P less than 0.05) in the oxycodone plus fentanyl group than in the buprenorphine group. The respiratory rate in the recovery room was lower among patients given buprenorphine, and two patients given buprenorphine developed severe respiratory depression. In the ward (2 to 24 h after operation) sublingual buprenorphine provided pain relief as good as intramuscularly administered oxycodone. No differences were noted in the incidence or severity of emetic symptoms between the groups. It is concluded that buprenorphine can provide good postoperative pain relief for gynaecological laparotomies performed under light isoflurane anaesthesia, but patients need to be monitored carefully after operation because of the possibility of respiratory depression.

Influence of buprenorphine on acute experimental pancreatitis

Abstract: Buprenorphine (15 µg/kg b.wt. per hour) distinctly reduced pain sensitivity in acute 3% sodium-taurocholate pancreatitis in male Wistar rats without interfering with the course of the disease. This was seen by assessment of enzyme elevation in serum and ascites and by histological evaluation of the pancreas. Buprenorphine is therefore recommended for animal experiments to study the effect of therapeutic principles in acute pancreatitis.

Side-effect problems of μ and κ agonists in clinical use

Abstract: Summary It is generally accepted that opioid analgesics act at heterogeneous receptors in the CNS. The functional role of different receptor subgroups in man is uncertain. Nevertheless, it is clear that drugs which act on μ-and κ -receptors can mediate analgesia, and opioid analgesics can be classified by their primary actions at these sites (either as agonists or partial agonists). Nevertheless, the limitations of this classification should be recognized, since most analgesics have multiple effects on different opioid receptors. Morphine and similar drugs are typical agonists at μ-receptors, although they also act at κ -receptors. They characteristically produce typical opiate effects (e.g. subjective central effects, tolerance and dependence, respiratory depression, nausea and vomiting, pupillary constriction, hypothermia, hypotension, decreased intestinal motility, biliary and ureteric spasm, and effects on endocrine function). Partial agonists at μ-receptors (e.g. buprenorphine and meptazinol) and drugs that act at κ -receptors (e.g. pentazocine, butorphanol, and nalbuphine) produce qualitatively similar effects although there are important differences between them. Some of them produce dysphoria and psychotomimetic phenomena, although tolerance and dependence are usually mild, and they have a relatively low abuse potential. The dose-response relationship for respiratory depression is usually shallow, and a plateau or ceiling effect may be present. Nausea and vomiting are relatively common, and a biphasic effect on pupillary diameter can sometimes be demonstrated. They are less likely to cause significant histamine release than morphine and pethidine. Nevertheless, some of them (e.g. pentazocine, butorphanol) can cause pulmonary hypertension. Their effects on the gut, the urinary tract, and the endocrine system are usually less marked. In conclusion, they may be less liable to produce adverse side-effects than classical μ-agonists, and in selected circum-stances their use may be associated with therapeutic advantages.

Intramuscular buprenorphine compared with morphine for postoperative analgesia

Abstract: CITATION: Payne, K. A., Murray, W. B. & Barrett, H. 1987. Intramuscular buprenorphine compared with morphine for postoperative analgesia. South African Medical Journal, 71:359-361.

[Buprenorphine in cancer pain: cross comparison with pentazocine].

Abstract: In a randomized cross-study analgesic activity and side effects of two narcotics, buprenorphine and pentazocine, administered orally in 91 advanced cancer patients whose pain intensity varied from moderate to severe, have been compared. The number of hours of sleep and hours standing after administration of both the drugs were also assessed and in 16 patients life activity was taken into consideration. The analysis of data showed: a better pain control with buprenorphine, than with pentazocine, with a statistically significant difference of P less than 0.001; an increase in the number of hours of sleep with buprenorphine, in comparison with pentazocine, with P less than 0.001; an increase in the number of hours standing with buprenorphine, in comparison with pentazocine; as for side effects, many more patients had to stop treatment with pentazocine than with buprenorphine.

Buphrenorphine: Detoxification after maintenance treatment

Abstract: Buprenorphine, a partial opiate agonist, has shown promise as a new drug for the maintenance, treatment and detoxification of heroin addictions. In this double blind study 15 outpatient heroin addicts were stabilised on sublingual buprenorphine (4mg/day) and then the effects of a 30 day gradual detoxification were assessed. For the first 2 weeks of the study, while taking 4mg of buprenorphine subjects reported symptoms of opiate intoxication and withdrawal, 2–4 and 8–9 hours respectively after each day's dose. During this time 12 of the 15 subjects had one or more opiate positive urine specimens and 48% of all urine specimens were opiate positive. As detoxification progressed subjects reported an earlier onset and a greater number of withdrawal symptoms. In addition they requested symptomatic treatment. The prescription of dextropropoxyphene napsylate (up to 800mg per day) and clonidine hydrochloride (up to 450mcg per day) controlled the subjects' withdrawal discomfort. Of the 6 subjects who completed the...

Quantification of the morphine reversal activity of opioid agonists/antagonists and naloxone by using a rabbit tooth pulp procedure

Abstract: The rabbit tooth pulp procedure was used to determine the potencies and durations of morphine reversal by naloxone, buprenorphine, nalbuphine, butorphanol, and pentazocine. Cumulative doses (mg/kg) required to double the number of morphine-depressed respirations per minute (RPM) (ED 2 X) and to reduce morphine-elevated lick/chew (L/C) volts by one-half (ED 1/2) were determined. These doses were naloxone 0.003, 0.013; buprenorphine 0.030, 0.130; nalbuphine 0.130, 0.520; butorphanol 0.120, 0.630; pentazocine 1.10, 0.150. The antinociceptive effects of these compounds were compared by determining the cumulative dose required to achieve the highest percentage maximum possible effect (% MPE) as determined by the elevation of lick/chew threshold volts from control volts in morphine-free rabbits: naloxone 6% at 0.0005 mg/kg; buprenorphine 69% at 0.075 mg/kg; nalbuphine 32% at 0.150 mg/kg; butorphanol 32% at 0.150 mg/kg, and pentazocine 12% at 1.55 mg/kg. The durations (min) of reversal of morphine RPM and morphine L/C volts were also determined: naloxone 33, 30; buprenorphine 240, 240; nalbuphine 120, 120; butorphanol 90, 45; pentazocine 60, 15. It is suggested that the rabbit tooth pulp assay is a sensitive and reliable assay to evaluate and quantitate compounds for opioid agonist/antagonist activity.

Epidural buprenorphine for postoperative analgesia

Abstract: patients should have blood values within the normal range. It might therefore be possible by their ommission both to avoid the inconvenience to the patients and to save the budget for these blood tests without endangering the patient. The patients were divided into two groups according to simple criteria: patients were classified as i l l on the basis of daily need for drugs (apart from minor tranquillisers or the contraceptive pill). insulin or oral hypoglycaemic drugs, or thc prcsencc of a diagnosis of neoplastic disease. Of the patient sample. 1099 were defined as ill and 3407 as healthy. The deviations of values for haemoglobin. packed ccll volume and serum creatinine from the reference ranges employed by this hospital were calculated (Figs. 1 and 2). It was concluded that determination of these variables is unnecessary in hkalthy patients under the age of 50 years. However, the information desired about these values must, of course, depend upon the extent and nature of the planned surgery. In addition. one parameter of haemoglobin or packed ccll volume is sufficient, since i t is possible to calculate the other as haematocrit = 0.07 + 0.04 x haemoglobin mmol:litre (haemoglohin gidl x 0.6206 = haemoglobin mmoljlitre) in I.he reference range.