morphinans and dihydrocodeine

A randomized, double-blind comparison of nalbuphine 30 mg or 60 mg by mouth and dihydrocodeine 30 mg by mouth was conducted in 75 patients with moderate to severe pain after surgery for dental extractions under general anaesthesia. A significant reduction in pain intensity followed each treatment and persisted throughout the 4-h observation period after nalbuphine, but only for 3 h after dihydrocodeine was given. Reduction in pain intensity was significantly greater 2, 3 and 4 h after the use of nalbuphine 60 mg than following dihydrocodeine 30 mg, and the mean total pain intensity difference was greater following nalbuphine 60 mg than following dihydrocodeine. Nalbuphine 60 mg effectively provided complete or good pain relief in more than 50% of the patients and only three patients in this group required additional analgesia during the period of observation, compared with nine patients in each of the other groups. However, the patients who received nalbuphine 30 mg had a significantly higher mean pain intensity before treatment than those in the other groups. The side-effects encountered were those typical of opioid medication; there were no statistically significant differences between the groups.

Topics: Administration, Oral; Adolescent; Adult; Anesthesia, Dental; Anesthesia, General; Clinical Trials as Topic; Codeine; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Random Allocation; Time Factors; Tooth Extraction

The effect of sublingual buprenorphine (0.4 mg) was compared with that of oral dihydrocodeine (60 mg) in patients experiencing post-operative pain following general surgery. Pain relief was significantly greater for buprenorphine than for dihydrocodeine, based on both peak effect and total effect. Both treatments were effective from 30 minutes. There was evidence that buprenorphine and a slightly slower onset of action, but a distinctly longer duration of action, than dihydrocodeine. Unwanted effects were similar for both treatments.

Topics: Administration, Oral; Buprenorphine; Codeine; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Random Allocation

Urine drug testing of pain patients provides objective information to health specialists regarding patient compliance, diversion, and concurrent illicit drug use. Interpretation of urine test results for semi-synthetic opiates can be difficult because of complex biotransformations of parent drug to metabolites that are also available commercially and may be abused. Normetabolites such as norcodeine, norhydrocodone and noroxycodone are unique metabolites that are not available commercially. Consequently, detection of normetabolite in specimens not containing parent drug, provides conclusive evidence that the parent drug was consumed. The goal of this study was to evaluate the prevalence and patterns of the three normetabolites, norcodeine, norhydrocodone and noroxycodone, in urine specimens of pain patients treated with opiates. Urine specimens were hydrolyzed with beta-glucuronidase and analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) assay for the presence of codeine, norcodeine, morphine, hydrocodone, norhydrocodone, hydromorphone, dihydrocodeine, oxycodone, noroxycodone, and oxymorphone. The limit of quantitation (LOQ) for these analytes was 50ng/mL. The study was approved by an Institutional Review Board. Of the total specimens (N=2654) tested, 71.4% (N=1895) were positive (>or=LOQ) for one or more of the analytes. The prevalence (%) of positive results for codeine, hydrocodone and oxycodone was 1.2%, 26.1%, and 36.2%, respectively, and the prevalence of norcodeine, norhydrocodone and noroxycodone was 0.5%, 22.1%, and 31.3%, respectively. For specimens containing normetabolite, the prevalence of norcodeine, norhydrocodone and noroxycodone in the absence of parent drug was 8.6%, 7.8% and 9.4%, respectively. From one-third to two-thirds of these specimens also did not contain other metabolites that could have originated from the parent drug. Consequently, the authors conclude that inclusion of norcodeine, norhydrocodone and noroxycodone is useful in interpretation of opiate drug source and reduces potential false negatives that would occur without tests for these unique metabolites.

Topics: Analgesics, Opioid; Chromatography, Liquid; Codeine; False Negative Reactions; Forensic Toxicology; Humans; Hydrocodone; Medication Adherence; Morphinans; Oxycodone; Oxymorphone; Pain; Tandem Mass Spectrometry

Dextromethorphan, dimemorfan, dihydrocodeine and oxymethebanol, centrally acting antitussives, were examined for their effect on Ehrlich carcinoma cells and sarcoma-180 cells in vitro or in vivo. The tumor cells were suspended in Hanks balanced salt solution (pH 7.4) supplemented with 2% bovine albumin, and they were incubated with and without 1 mM drugs at 37 degrees C for 120 min. The incubation of the tumor cells with dextromethorphan or dimemorfan resulted in a decrease in the proportion of the viable cells (less than 25% after 120 min). However, no significant change was observed in the proportion of the viable tumor cells during the incubation with and without the other drugs (80-83% after 120 min). In addition, mice given the tumor cells i.p. were injected intraperitoneally with drugs (20-80 mg/kg/day) once daily for 5 successive days, and their survival time was observed. There was a slight difference in the survival time between mice treated with and without dextromethorphan or dimemorfan. However, a significant difference was found in the survival time between mice treated with and without dextromethorphan when mice given Ehrlich carcinoma cells were injected with the drug (40 mg/kg/time) twice a day for 5 days (about 18 days and 29 days). These results indicate that dextromethorphan and dimemorfan are cytotoxic to the tumor cells in vitro and in vivo.

Topics: Animals; Antineoplastic Agents; Antitussive Agents; Carcinoma, Ehrlich Tumor; Cell Survival; Cells, Cultured; Codeine; Dextromethorphan; Female; Mice; Morphinans; Sarcoma 180; Thebaine