morphinans and Respiratory-Insufficiency

The new benzodiazepine antagonist flumazenil represents another approach to the ever-present problem of recurring respiratory depression after anesthesia with flunitrazepam and fentanyl. Objective and subjective side effects of flumazenil were studied in comparison with the opiate antagonists naloxone and nalbuphine. METHODS. One hundred fifty surgical patients, ASA I or II, aged 18-65 years were studied. After premedication with atropine 0.5 mg and flunitrazepam 0.5 mg anesthesia was induced with flunitrazepam 0.5 mg, fentanyl 0.1 mg and etomidate 10 mg and maintained with N2O/O2 2:1 and additional increments of 0.1 mg fentanyl as required. Relaxation for intubation and surgery was obtained with non depolarizing muscle relaxants. After the operation the patients were extubated and then flumazenil 0.4 mg, naloxone 0.05 mg, or nalbuphine 20 mg was given i.v. (randomized and double-blind). In 15 patients blood pressure and heart rate were monitored. In all patients postoperative pain was assessed by the time interval between administration of the antagonist and need for the first analgesic medication. On the 1st postoperative day recall of postoperative events and of pictures shown 5, 30, 60, 120, and 240 min after administration of the antagonist was tested. The patients were interviewed a second time for side effects on day 3-6 after the operation. RESULTS. The three antagonists produced no significant effects on arterial pressure and heart rate. There were no differences between the antagonists in the incidence of postoperative nausea and/or vomiting or postoperative pain. After flumazenil, a significant transient increase in vigilance and better recall of postoperative events was noted within 5 and 30 min after administration of the drug. CONCLUSION. On the basis of the objective clinical findings, there is no reason to prefer either benzodiazepine or opiate antagonists after flunitrazepam and fentanyl. However, postoperative amnesia can be reduced by flumazenil if this is desirable.

Topics: Adult; Double-Blind Method; Fentanyl; Flumazenil; Flunitrazepam; Humans; Middle Aged; Morphinans; Nalbuphine; Naloxone; Randomized Controlled Trials as Topic; Respiratory Insufficiency

The efficacy of nalbuphine, an agonist/antagonist opioid, in preventing respiratory depression from epidural morphine analgesia after thoracotomy, was assessed in a randomized double-blind placebo controlled trial. After a standardized general anaesthetic and 0.15 mg.kg-1 of epidural morphine, patients received a bolus and then a 24 h infusion of nalbuphine (200 micrograms.kg-1 + 50 micrograms.kg-1.hr-1, 100 micrograms.kg-1 + 25 micrograms.kg-1.hr-1, or 50 micrograms.kg-1 + 12.5 micrograms.kg-1.hr-1) or placebo. Blood gases, analgesia, sedation, side effects, and blood nalbuphine concentrations were assessed every two hours for the next 24 h. Fifty-three per cent of placebo-treated patients had a PaCO2 greater than 50 mmHg and 89 per cent of these received naloxone. A 200 micrograms.kg-1 bolus of nalbuphine followed by a 50 micrograms.kg-1.hr-1 infusion achieved a mean steady state blood level of 38.2 ng.ml-1 and prevented CO2 retention greater than 50 mmHg in all but two patients, neither of whom required naloxone. There was no difference in the incidence of side effects among groups, and analgesia appeared to be unaffected by nalbuphine.

Topics: Adult; Aged; Analgesia, Epidural; Carbon Dioxide; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Morphinans; Morphine; Nalbuphine; Pain, Postoperative; Placebos; Respiratory Insufficiency; Thoracotomy

The degree of respiratory depression caused by buprenorphine and tramadol were studied in two groups of 25 patients each by means of Read's re-breathing technique. The estimations were made during the immediate postoperative stage in order to include potential residual effects of the general anaesthesia. The slope of the CO2 curve as a measure of respiratory depression decreased by 27 per cent after administration of 0.3 mg of buprenorphine, a reduction which equals that produced by potent morphine-type analgesics. The response to 50 mg of tramadol was a non-significant decrease by 3 per cent. At doses mentioned buprenorphine produced reliable pain relief, whereas with tramadol the failure rate was 28 per cent. There was no difference between the two drugs in respect of circulatory reactions and side-effects. Despite its depressing effect on the respiration (an action it shares with all potent analgesics) buprenorphine is a very useful analgesic because it provides excellent pain relief, has no or only minimal addictive properties and is not subject to the Dangerous Drugs Act.

Topics: Analgesia; Anesthesia, General; Buprenorphine; Carbon Dioxide; Cyclohexanols; Female; Humans; Male; Morphinans; Postoperative Period; Respiration; Respiratory Insufficiency; Tramadol

Doxapram administered as a single injection or infusion satisfactorily counteracted the respiratory depression produced by buprenorphrine when administered one hour after the analgesic in healthy subjects. The respiratory stimulant effect was relatively short lived, however, a more prolonged effect was found by study of the displacement of the carbon dioxide response curve.

Topics: Adult; Analgesics; Blood Pressure; Carbon Dioxide; Clinical Trials as Topic; Doxapram; Heart Rate; Humans; Male; Morphinans; Pupil; Respiratory Function Tests; Respiratory Insufficiency

Topics: Analgesics, Opioid; Animals; beta-Arrestin 2; Blood-Brain Barrier; Congresses as Topic; Dopamine; Drug Overdose; Humans; Morphinans; Oxycodone; Receptors, Opioid, mu; Respiratory Insufficiency

Aminomorphinans are a relatively young class of opioid drugs among which substances of high in vitro efficacy and favorable in vivo action are found. We report the synthesis and pharmacological evaluation of novel 6β-acylaminomorphinans. 6β-Morphinamine and 6β-codeinamine were stereoselectively synthesized by Mitsunobu reaction. The aminomorphinans were subsequently acylated with diversely substituted cinnamic acids. In vitro binding studies on cinnamoyl morphinamines showed moderate affinity for all opiate receptors with some selectivity for mu opioid receptors, while cinnamoyl codeinamines only showed affinity for mu opioid receptors. In vivo analgesia studies showed significant analgesic activity of 6β-cinnamoylmorphinamine mediated by mu and delta receptors. The lead compound was found to be roughly equipotent to morphine (ED₅₀ 3.13 ± 1.09 mg/kg) but devoid of the dangerous side-effect respiratory depression, a major issue associated with traditional opioid therapy.

Topics: Analgesics; Animals; Dose-Response Relationship, Drug; Hot Temperature; Mice; Molecular Structure; Morphinans; Morphine; Narcotic Antagonists; Pain Measurement; Pain Threshold; Receptors, Opioid; Respiratory Insufficiency; Structure-Activity Relationship; Time Factors

Topics: Analgesia, Epidural; Analgesics; Fentanyl; Humans; Morphinans; Morphine; Nalbuphine; Respiratory Insufficiency; Sufentanil

The use of epidural opioids for postoperative analgesia has been associated with respiratory depression. This report demonstrates the ability of nalbuphine to rapidly reverse the respiratory depression caused by epidural sufentanil while maintaining postoperative pain relief.

Topics: Aged; Female; Fentanyl; Humans; Injections, Epidural; Morphinans; Nalbuphine; Respiratory Insufficiency; Sufentanil

Examination of haemodynamic changes, after 20 mg nalbuphine had been administered IV to 11 ventilated patients with acute respiratory failure, showed that on average pulmonary arterial mean pressure increased by 8% of the initial value. This increase was reversed after the test dosage was doubled from 20 mg to 40 mg nalbuphine. Regression analysis of the correlation between changes in pulmonary arterial mean pressure and patient age resulted in an increase in mean pressure by 0.1 mmHg per year after 20 mg nalbuphine. These findings suggest that nalbuphine must be carefully monitored in elderly and pulmonary risk patients.

Topics: Adolescent; Adult; Aged; Hemodynamics; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Respiration, Artificial; Respiratory Insufficiency

Topics: Humans; Morphinans; Nalbuphine; Postoperative Complications; Respiratory Insufficiency; Time Factors

Topics: Adult; Aged; Female; Humans; Male; Morphinans; Nalbuphine; Postoperative Complications; Respiratory Insufficiency; Time Factors

Topics: Aged; Female; Heroin; Humans; Morphinans; Nalbuphine; Postoperative Complications; Respiratory Insufficiency; Time Factors

Topics: Anti-Anxiety Agents; Benzodiazepines; Buprenorphine; Humans; Morphinans; Postoperative Complications; Respiratory Insufficiency

Buprenorphine was given intravenously to produce analgesia in the immediate postoperative period, the dose being titrated against the response of each patient in order to obtain complete freedom from pain. In 50 patients following lower segment Caesarean section under general anaesthesia, buprenorphine in the dose range 0.4-7.0 mg was found to be a potent, long lasting and safe analgesic. Serial blood gas estimations performed on ten of the patients confirmed the clinically observed lack of respiratory depression.

Topics: Adult; Buprenorphine; Cesarean Section; Dose-Response Relationship, Drug; Female; Humans; Morphinans; Pain, Postoperative; Pregnancy; Respiratory Insufficiency; Time Factors

Topics: Age Factors; Aged; Buprenorphine; Female; Hemodynamics; Humans; Male; Morphinans; Respiratory Insufficiency

Buprenorphine, a partial opiate-receptor agonist with potent analgesic properties, was given to 7548 patients in the immediate postoperative period. Ninety per cent of patients had good or adequate pain relief for at least 4 hours; there were few adverse effects and the incidence of drug-associated respiratory depression was estimated at less than 1%. There were no other side-effects of clinical note.

Topics: Adolescent; Adult; Aged; Buprenorphine; Child; Child, Preschool; Drug Evaluation; Female; Humans; Male; Middle Aged; Morphinans; Nausea; Pain, Postoperative; Respiratory Insufficiency; Time Factors; Vomiting

Topics: Buprenorphine; Heroin; Humans; Morphinans; Myocardial Infarction; Respiratory Insufficiency

Topics: Acidosis; Blood Proteins; Buprenorphine; Female; Humans; Middle Aged; Morphinans; Postoperative Complications; Protein Binding; Respiratory Insufficiency; Time Factors

Topics: Acepromazine; Animals; Cattle; Cattle Diseases; Diprenorphine; Drug Combinations; Etorphine; Male; Morphinans; Respiratory Insufficiency

Topics: Acute Disease; Aged; Aging; Bronchitis; Chronic Disease; Cough; Drug Combinations; Humans; Laryngitis; Morphinans; Pentylenetetrazole; Pharyngitis; Respiratory Insufficiency