morphinans and Vomiting

Topics: Analgesics; Blood Circulation; Fentanyl; Humans; Intestines; Levallorphan; Meperidine; Methadone; Methotrimeprazine; Morphinans; Morphine; Nalorphine; Narcotic Antagonists; Nausea; Pain; Pentazocine; Psychopharmacology; Respiration; Substance-Related Disorders; Urinary Tract; Vomiting

Chemotherapy induced nausea and vomiting (CINV) remains a major problem that seriously impairs the quality of life (QoL) in cancer patients receiving chemotherapy regimens. Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. A randomized, placebo-controlled Phase III study was conducted to evaluate the efficacy of a complex homeopathic medicine, Cocculine, in the control of CINV in non-metastatic breast cancer patients treated by standard chemotherapy regimens.. Chemotherapy-naïve patients with non-metastatic breast cancer scheduled to receive 6 cycles of chemotherapy including at least three initial cycles of FAC 50, FEC 100 or TAC were randomized to receive standard anti-emetic treatment plus either a complex homeopathic remedy (Cocculine, registered in France for treatment of nausea and travel sickness) or the matching placebo (NCT00409071 clinicaltrials.gov). The primary endpoint was nausea score measured after the 1st chemotherapy course using the FLIE questionnaire (Functional Living Index for Emesis) with 5-day recall. Secondary endpoints were: vomiting measured by the FLIE score, nausea and vomiting measured by patient self-evaluation (EVA) and investigator recording (NCI-CTC AE V3.0) and treatment compliance.. From September 2005 to January 2008, 431 patients were randomized: 214 to Cocculine (C) and 217 to placebo (P). Patient characteristics were well-balanced between the 2 arms. Overall, compliance to study treatments was excellent and similar between the 2 arms. A total of 205 patients (50.9%; 103 patients in the placebo and 102 in the homeopathy arms) had nausea FLIE scores > 6 indicative of no impact of nausea on quality of life during the 1st chemotherapy course. There was no difference between the 2 arms when primary endpoint analysis was performed by chemotherapy stratum; or in the subgroup of patients with susceptibility to nausea and vomiting before inclusion. In addition, nausea, vomiting and global emesis FLIE scores were not statistically different at any time between the two study arms. The frequencies of severe (Grade ≥ 2) nausea and vomiting were low in our study (nausea: P: 17.6% vs C: 15.7%, p=0.62; vomiting: P: 10.8% vs C: 12.0%, p=0.72 during the first course).. This double-blinded, placebo-controlled, randomised Phase III study showed that adding a complex homeopathic medicine (Cocculine) to standard anti-emetic prophylaxis does not improve the control of CINV in early breast cancer patients.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Breast Neoplasms; Double-Blind Method; Female; Humans; Middle Aged; Morphinans; Plant Extracts; Quality of Life; Vomiting; Young Adult

We prospectively investigated the efficacy of opioid rotation from oral morphine to oral oxycodone in cancer patients who had difficulty in continuing oral morphine treatment because of inadequate analgesia and/or intolerable side effects.. Twenty-seven patients were enrolled and 25 were evaluated. The rate of patients who achieved adequate pain control, which provided an indication of treatment success, was evaluated as primary endpoint. The acceptability and pharmacokinetics of oxycodone were evaluated in addition to the assessment of analgesic efficacy and safety during the study period.. In spite of intense pain, the morphine daily dose could not be increased in most patients before the study because of intolerable side effects. However, switching to oral oxycodone allowed approximately 1.7-fold increase as morphine equivalent dose. Consequently, 84.0% (21/25) of patients achieved adequate pain control. By the end of the study, all patients except one had tolerated the morphine-induced intolerable side effects (i.e. nausea, vomiting, constipation, drowsiness). Common side effects (>10%) that occurred during the study were typically known for strong opioid analgesics, and most were mild to moderate in severity. A significant negative correlation between creatinine clearance (CCr) value and the trough concentrations of the morphine metabolites was observed. On the other hand, no significant correlation was found between CCr value and the pharmacokinetic parameters of oxycodone or its metabolites.. For patients who had difficulty in continuing oral morphine treatment, regardless of renal function, opioid rotation to oral oxycodone may be an effective approach to alleviate intolerable side effects and pain.

Topics: Administration, Oral; Aged; Analgesics, Opioid; Constipation; Drug Administration Schedule; Female; Humans; Linear Models; Male; Middle Aged; Morphinans; Morphine; Morphine Derivatives; Nausea; Neoplasms; Oxycodone; Pain; Prospective Studies; Renal Insufficiency, Chronic; Sleep Stages; Treatment Outcome; Vomiting

Thirty patients with cancer pain completed a double-blind crossover study comparing controlled-release (CR) and immediate-release (IR) oxycodone. In open-label titration (2 to 21 days), these patients were stabilized on IR oxycodone qid. They were then randomized to double-blind treatment with CR oxycodone q12h or IR oxycodone qid for 3 to 7 days followed by crossover at the same daily dose. Mean (+/- SD) pain intensity (0 = none to 10 = severe) decreased from a baseline of 6.0 +/- 2.2 to 2.7 +/- 1.1 after titration with IR oxycodone dosed qid. Pain intensity remained stable throughout double-blind treatment: 2.7 +/- 1.9 with CR oxycodone and 2.8 +/- 1.9 with IR oxycodone. Acceptability of therapy and pain scores correlated with plasma oxycodone concentrations for each interval and were similar for both medications (IR and CR oxycodone). Adverse events were similar for both formulations. Following repeat dosing under double-blind conditions, oral CR oxycodone administered q12h provided analgesia comparable to IR oxycodone given qid.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Biological Availability; Chronic Disease; Cross-Over Studies; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Morphinans; Neoplasms; Oxycodone; Oxymorphone; Pain; Pain Measurement; Therapeutic Equivalency; Vomiting

Seventy institutionalized severely and profoundly retarded patients were administered intramuscular butorphanol, 1.0 to 4.0 mg, for premedication prior to dental procedures. These patients had been refractory to previous combined chloral hydrate and diphenhydramine treatment. Clinical efficacy was categorized according to the extent that adjunctive restraints were required to accomplish the dental procedure. A total of 151 butorphanol trials were recorded. Butorphanol was observed to be clinically effective in 74.8% of the administrations and sedation was observed in 28.2% of the trials. Dosage titration increased efficacy to 85.0%. Contribution of concurrent central nervous system depressant medication to clinical efficacy and dose requirements lacked statistical significance; however, a strong trend (p = 0.068) was found in the medication-free group with higher dosage. Vomiting (2.6%) was the most frequent adverse effect observed. One patient had marked cardiorespiratory depression that was promptly reversed by intravenous naloxone. Two patients experienced mild hypotensive episodes immediately following injection, but they recovered uneventfully. Butorphanol was shown to be a safe and effective agent for dental premedication in this difficult patient population.

Topics: Adolescent; Adult; Butorphanol; Clinical Trials as Topic; Dental Care for Disabled; Female; Humans; Injections, Intramuscular; Intellectual Disability; Male; Middle Aged; Morphinans; Preanesthetic Medication; Restraint, Physical; Vomiting

In a randomized double-blind placebo-controlled trial involving 80 patients nalbuphine 10 mg and 20 mg were compared with pethidine 100 mg and a placebo given i.m. at least 90 min before minor gynaecological surgery. Nalbuphine proved a suitable alternative to pethidine, producing beneficial sedation which was maximum at 60 min after injection. Both nalbuphine and pethidine reduced the excitatory sequelae of methohexitone induction. Increasing the dose of nalbuphine from 10 mg to 20 mg produced no significant additional sedation or intraoperative benefit. Short-lived pain at the injection site was a feature of the use of nalbuphine in either dose. The main disadvantage of nalbuphine was nausea and vomiting of delayed onset, the frequency of which was similar after either dose.

Topics: Adult; Clinical Trials as Topic; Female; Humans; Meperidine; Morphinans; Nalbuphine; Nausea; Postoperative Complications; Preanesthetic Medication; Vomiting

The safety and efficacy of single intramuscular doses of dezocine (10 or 15 mg) were compared with butorphanol (2 mg) and placebo in 157 patients with moderate to severe postoperative pain. A verbal pain intensity scale, an analog pain intensity scale, and a verbal pain relief scale were used to record the patients' subjective assessments. The results of this study indicate that a single 10 or 15 mg intramuscular injection of dezocine is safe and more effective than placebo for four to six hours, respectively, in the treatment of moderate to severe postoperative pain (P less than .05). During the first hour of treatment the pain relief afforded by 2 mg of butorphanol was significantly greater than that afforded by 10 mg of dezocine (P less than .05), but both doses of dezocine provided long-lasting relief. The scores on all three efficacy scales were highest with the 15 mg dose of dezocine after the first hour, while the 10 mg dose of dezocine and butorphanol were compared during this period. Nausea and vomiting were the most commonly reported side effects; injection site reactions were reported more frequently in the butorphanol group.

Topics: Acute Disease; Adolescent; Adult; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Clinical Trials as Topic; Consumer Behavior; Cycloparaffins; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Nausea; Pain, Postoperative; Placebos; Tetrahydronaphthalenes; Time Factors; Vomiting

A randomized double-blind cross-over study was performed to evaluate the possible anti-emetic effect of the partial opiate antagonist buprenorphine in comparison to domperidone in chemotherapy-induced nausea and vomiting. Emesis was of significantly shorter duration on domperidone treatment. Most patients preferred domperidone, mainly due to adverse side-effects of buprenorphine. Nevertheless, emesis in buprenorphine treatment was less disabling. Therefore, it might be useful to search for new alternatives in this group of drugs or to use them in a combination regimen of anti-emetic agents.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Buprenorphine; Clinical Trials as Topic; Domperidone; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Nausea; Pilot Projects; Random Allocation; Vomiting

A double-blind comparison of some analgesic and gastrointestinal effects of nalbuphine and pethidine was performed in 28 women undergoing laparoscopic sterilisation. The opioid was given as an initial loading dose prior to the induction of general anaesthesia and further doses were given on demand in the postoperative period to achieve and maintain adequate pain relief. Gastric emptying in the immediate postoperative period was also assessed in each patient by measuring the rate of absorption of orally administered paracetamol. Nalbuphine was equally effective as pethidine as a postoperative analgesic, but may have been a less effective supplement to anaesthesia in the doses used in this study. Gastric emptying was profoundly depressed in all patients irrespective of which analgesic was used.

Topics: Absorption; Acetaminophen; Adult; Animals; Double-Blind Method; Drug Evaluation; Female; Gastric Emptying; Humans; Meperidine; Morphinans; Nalbuphine; Pain, Postoperative; Random Allocation; Vomiting

Buprenorphine was used as an analgesic medication for patients at the pain clinic. Clinical observations on its long term administration for intractable pain are reported. A good analgesic activity was noted in most of the patients. Nausea and vomiting was the mean reason for cancellation of the therapy.

Topics: Administration, Oral; Adult; Aged; Analgesics; Clinical Trials as Topic; Confusion; Depression; Drug Evaluation; Female; Humans; Male; Middle Aged; Morphinans; Nausea; Pain; Sleep; Sweating; Time Factors; Vomiting

Topics: Adolescent; Adult; Aged; Blood Pressure; Cholecystectomy; Female; Humans; Isonipecotic Acids; Male; Meperidine; Middle Aged; Morphinans; Nausea; Nitriles; Pain; Piperidines; Pulse; Respiration; Vomiting

Topics: Administration, Oral; Adolescent; Adult; Aged; Analgesia; Clinical Trials as Topic; Female; Headache; Humans; Male; Middle Aged; Morphinans; Nausea; Pentazocine; Placebos; Time Factors; Vomiting

The new paradigm of precision medicine in oncology questions today the respective place of evidence-based medicine and doctor-patient relationship. Based on the results of a randomized study comparing the efficacy of a homeopathic molecule in the prevention of nausea and vomiting induced by chemotherapy in non-metastatic breast cancer, this article extends and develops the discussion of maintaining an unresolved tension between medical art and medical science, between care and cure. This tension sets a base for the authors of the therapeutic alliance in medicine, defined as a dialectic constantly adjourned between the alliance of the doctor with the patient and his therapy, and the therapeutic effect of this alliance. Because if a policy or a public opinion were to promote an exclusively rational medicine deprived of the field of relation to care, or on the contrary a medicine based only on clinical sense and intuition, then respectively the ethics of care and the progress of therapy would be threatened. It is advisable to be aware of erring from the truth, amplified today by social networks, as much due to a tide of scientific positivism, as an excess of the "good caring soul". Taking into account the therapeutic alliance makes it possible to no longer oppose scientific medicine and care relationship.

Topics: Breast Neoplasms; Delivery of Health Care; Evidence-Based Medicine; Female; Humans; Materia Medica; Medicine; Metaphor; Morphinans; Nausea; Online Social Networking; Physician-Patient Relations; Precision Medicine; Proof of Concept Study; Randomized Controlled Trials as Topic; Science; Therapeutic Alliance; Vomiting

Opioid-induced bowel syndromes deteriorate patients' quality of life and may lead to nonadherence to opioid schedule and under-treatment of pain. The objective was to characterize the pharmacological profile of 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-6'-ethoxycarbonyl-3,14-dihydroxyindolo [2',3'-6,7]morphinan (TAN-452), a novel peripherally acting opioid receptor antagonist.. The in vitro binding affinity for the μ-, δ-, and κ-opioid receptors (MOR, DOR, and KOR) and the inhibition of [. TAN-452 is a peripherally acting opioid receptor antagonist with selectivity for DOR that attenuates morphine-induced side effects, such as nausea, vomiting, and constipation, without affecting pain control.

Topics: Analgesics, Opioid; Animals; Brain; Constipation; Ferrets; Gastrointestinal Diseases; Gastrointestinal Transit; Humans; Indoles; Male; Morphinans; Morphine; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Receptors, Opioid, delta; Tissue Distribution; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Breast Neoplasms; Female; Humans; Morphinans; Plant Extracts; Vomiting

A therapeutic regimen is described for sedative, analgesic, and anti-emetic effect in patients receiving intra-arterial carmustine (BCNU) for malignant gliomas. This regimen consists of nalbuphine, 30 mg, i.v., and droperidol, 2.5 mg, i.v., given immediately prior to intra-carotid BCNU infusion. Droperidol, 2.5 mg, i.v., is then administered on four hour intervals for sixteen hours post-procedure. This combination provided excellent effect in nine patients treated for twelve intra-carotid infusions. None of the nine patients experienced vomiting, one experienced mild nausea several hours post-infusion, and non complained of severe pain or discomfort. Thirteen additional patients received diazepam, 10 mg, P.O., prior to the intra-carotid BCNU infusion, with fentanyl, 100 mcg, i.v., and prochlorperazine, 10 mg, i.m. at the onset of infusion. All thirteen patients suffered from severe nausea, vomiting, and orbital pain. The nalbuphine/droperidol combination is thought to provide a superior alternative to the traditional narcotic/pheonothiazine/benzodiazepine combination for carotid BCNU infusion. This combination has theoretical advantages for the patient with intracranial mass lesions by providing analgesia and sedation with minimal potential for respiratory depression and carbon dioxide retention.

Topics: Adult; Aged; Brain Neoplasms; Carmustine; Carotid Arteries; Diazepam; Droperidol; Drug Therapy, Combination; Fentanyl; Glioma; Humans; Injections, Intra-Arterial; Middle Aged; Morphinans; Nalbuphine; Nausea; Prochlorperazine; Vomiting

The analgesic agent butorphanol was evaluated for its ability to block cisplatin-induced emesis in ferrets and dogs. In ferrets, butorphanol (0.15, 0.3, or 0.45 mg/kg; expressed in terms of the tartrate salt) administered sc 30 minutes prior to cisplatin (8 mg/kg iv) reduced the number of emetic episodes but did not eliminate them. When these doses of butorphanol were administered 30 minutes before and 30 and 90 minutes after cisplatin, they caused a dose-related reduction in the number of emetic episodes; there was complete protection at a dose of 0.45 mg/kg/injection. In dogs, butorphanol (0.185 or 0.37 mg/kg/injection, expressed in terms of the tartrate salt) was administered sc on the same multiple-dose schedule used in the ferrets; this caused a nearly complete elimination of the emetic response to cisplatin (3 mg/kg iv). Butorphanol caused some sedation in both species at effective antiemetic doses but had no effect on the antitumor activity of cisplatin against murine L1210 leukemia. Naloxone blocked the antiemetic effect of butorphanol in ferrets, indicating the involvement of opiate receptors. The results of these studies suggest that butorphanol may be useful clinically in mitigating the emetic effects of cisplatin.

Topics: Animals; Butorphanol; Cisplatin; Dogs; Dose-Response Relationship, Drug; Female; Ferrets; Male; Mice; Morphinans; Naloxone; Time Factors; Vomiting

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: Animals; Barium Sulfate; Bethanechol Compounds; Dogs; Duodenum; Emetics; Fluoroscopy; Gastrointestinal Motility; Morphinans; Muscle Contraction; Muscle, Smooth; Postoperative Complications; Pylorus; Stomach; Transducers; Vagotomy; Vomiting