morphine-6-glucuronide and Pruritus

The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of morphine and morphine 6-glucuronide (M6G) in children with cancer. Serum concentrations of morphine and M6G in children who received single oral or short term continuous intravenous morphine were determined by HPLC and ELISA assays, respectively. The serum C(max) of morphine and M6G after i.v. morphine administration was 560.5 and 309.0 nM and the T(max) was 61 and 65 min, respectively. The elimination half-life was 140.0 and 328.7 min, respectively. After oral administration of morphine, the serum C(max) of morphine and M6G was 408.34 and 256.3 nM and the T(max) was 40.0 and 60 min, respectively. The half-life was 131.0 and 325.8 min, respectively. The side effects were: drowsiness (100%), nausea and/or vomiting (57%), pruritus (28%) and urinary retention (14%). There were no reports of respiratory complications. This study showed that pharmacokinetics factors of morphine and M6G in children were significantly different from adults. Therefore the required dose for children should be different from that of adults and should be based on studies performed on children rather than on studies on adults. Some adverse effects, particularly nausea and pruritus, may be commoner than is usually thought, while others, particularly respiratory problems did not occur.

Topics: Administration, Oral; Adolescent; Biotransformation; Child; Child, Preschool; Female; Half-Life; Humans; Infusions, Intravenous; Male; Models, Biological; Morphine; Morphine Derivatives; Narcotics; Nausea; Neoplasms; Pain; Pain Measurement; Pruritus; Sleep Stages; Urinary Retention; Vomiting

Morphine has been the standard opioid in patient-controlled analgesia (PCA). Oxycodone, the analgesic potency of which in i.v. administration has been suggested to be slightly greater than that of morphine, has not yet been studied for its efficacy in PCA.. Fifty patients, undergoing a plastic reconstruction of the breast or a major operation of the vertebrae, such as lumbar spinal fusion, used PCA for postoperative pain. Patients were randomized to receive either morphine 45 microg/kg or oxycodone 30 microg/kg as i.v. bolus doses. Patients were assessed for pain with a visual analogue scale (VAS) and side effects at 3, 9 and 24 h. Venous blood samples for the measurement of plasma concentration of oxycodone and that of morphine and its metabolites were taken.. In this study patients needed, on average, the same amount of oxycodone and morphine in the recovery room and on the ward. There was no difference in the quality of analgesia (VAS) or incidence of side effects, such as nausea, vomiting, pruritus and urinary retention. The plasma concentrations of morphine-6-glucuronide showed that this metabolite might contribute to the analgesia resulting from morphine administration.. The same dose of intravenous oxycodone and morphine administered by PCA pump was needed for immediate postoperative analgesia. The two drugs appear to be equipotent.

Topics: Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Double-Blind Method; Female; Humans; Incidence; Injections, Intravenous; Lumbar Vertebrae; Male; Mammaplasty; Middle Aged; Morphine; Morphine Derivatives; Nausea; Oxycodone; Pain Measurement; Pain, Postoperative; Pruritus; Spinal Fusion; Therapeutic Equivalency; Urinary Retention; Vomiting

We examined the therapeutic potential of a proprietary Croton palanostigma extract (Zangrado(R)) in the management of emesis and itch.. Emesis was induced in ferrets with morphine-6-glucuronide (0.05 mg/kg sc) in the presence of Zangrado (3 mg/kg, ip) and the cannabinoid receptor 1 antagonist, AM 251 (5 mg/kg, ip). Topical Zangrado (1%) was assessed for anti-pruretic actions in the 5-HT-induced scratching model in rats and evaluated in capsaicin-induced gastric hyperemia as measured by laser doppler flow. In the ApcMinmouse model of precancerous adenomatosis polyposis, mice received Zangrado (100 mug/ml in drinking water) from the age of 6 - 16 weeks for effects on polyp number. In RAW 264.7 cells Zangrado was examined for effects on lipopolysaccharide-induced nitrite production.. Zangrado was a highly effective anti-emetic, reducing morphine-induced vomiting and retching by 77%. These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism. Itch responses were blocked in both the morphine and 5-HT models. Zangrado did not exacerbate the ApcMincondition rather health was improved. Capsaicin-induced hyperemia was blocked by Zangrado, which also attenuated the production of nitric oxide by activated macrophages.. Zangrado is an effective anti-emetic and anti-itch therapy that is devoid of common side-effects, cannabinoid-independent and broadly suppresses sensory afferent nerve activation. This complementary medicine represents a promising new approach to the management of nausea, itch and irritable bowel syndrome.

Topics: Animals; Antiemetics; Antipruritics; Cell Line; Croton; Ferrets; Male; Mice; Mice, Inbred C57BL; Morphine Derivatives; Nausea; Piperidines; Plant Extracts; Proanthocyanidins; Pruritus; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Vomiting

The common adverse effect of centrally-injected mu-opioid receptor (mu-OR) agonists is pruritus. This study was conducted using mice to examine whether different subtypes of mu-OR would be responsible for pruritus and analgesia. Intracisternal injections of morphine and morphine-6beta-glucronide (M6G), but not M3G, produced an antinociceptive effect. Morphine, but neither M6G nor M3G, induced facial scratching, a pruritus-related response. Facial scratching following morphine was not affected by the mu(1)-OR antagonist naloxonazine at doses that inhibited the antinociceptive effects. The results suggest that different subtype and/or splice variants of mu-OR are separately involved in pruritus and antinociception of opioids.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Dose-Response Relationship, Drug; Injections, Subcutaneous; Male; Mice; Mice, Inbred ICR; Morphine; Morphine Derivatives; Naloxone; Narcotic Antagonists; Pain Measurement; Pain Threshold; Pruritus; Receptors, Opioid, mu; Time Factors