methylnaltrexone and Vomiting

We examined the effect of methylnaltrexone on the incidence of postoperative nausea and vomiting in a prospective double-blind placebo controlled study. One hundred and twenty female patients undergoing laparoscopic major gynecological surgery were allocated randomly to receive either 20 mg methylnaltrexone or placebo IV at the end of surgery. Postoperative nausea and vomiting was evaluated for 6 h after admission to the PACU and assessed by number of episodes and degree of severity. The incidences of nausea and vomiting for the placebo group were 27 and 18 percent, respectively. The corresponding values for the methylnaltrexone group were 20 and 10 percent. We conclude that methylnaltrexone did not prevent nor significantly reduced the incidence and severity of postoperative nausea and vomiting following a balanced anesthetic technique in gynecological procedures.

Topics: Adult; Antiemetics; Double-Blind Method; Female; Humans; Middle Aged; Naltrexone; Narcotic Antagonists; Nausea; Postoperative Complications; Prospective Studies; Quaternary Ammonium Compounds; Vomiting

Topics: Abdominal Pain; Adult; Analgesics, Opioid; Anorexia; Chronic Disease; Diabetes Mellitus, Type 1; Drug Administration Schedule; Endoscopy, Gastrointestinal; Gastroparesis; Humans; Hypertension; Kidney Failure, Chronic; Male; Naltrexone; Narcotic Antagonists; Nausea; Neuralgia; Quaternary Ammonium Compounds; Substance Withdrawal Syndrome; Treatment Outcome; Vomiting

Topics: Aged; Constipation; Female; Humans; Naltrexone; Narcotic Antagonists; Palliative Care; Quaternary Ammonium Compounds; Vomiting

Morphine can have either an emetic or an antiemetic effect. The emetic effect of morphine can be blocked by methylnaltrexone (MNTX), a quaternary opioid antagonist with peripheral action. In this study, we tested the hypothesis that administering MNTX to block the peripheral emetic effect of morphine would unmask the central antiemetic effect of the morphine. The net result, we hypothesized, would be a reduction in apomorphine- or cisplatin-induced emesis.. MNTX 0.25 mg/kg and morphine 1 mg/kg were administered to conscious dogs which were then challenged with the potent emetic agents apomorphine or cisplatin. Emesis was assessed by the presence of characteristic retching motions accompanied by the regurgitation of gastric contents.. We observed that apomorphine challenges of 0.1 mg/kg and of 0.03 mg/kg produced 100% emesis in control animals. After pretreatment with MNTX and morphine, the frequency of emesis with the larger dose of apomorphine was reduced to 50% and with the smaller dose to 22%. MNTX alone did not block apomorphine-induced emesis. In animals challenged with cisplatin 3 mg/kg, the emetic response was 100%. Emesis did not occur in animals pretreated with MNTX 0.25 mg/kg and morphine 1 mg/kg before cisplatin.. Our results demonstrate that MNTX combined with morphine reduces apomorphine-induced emesis and blocks cisplatin-induced emesis. These results support the hypothesis that the emetic effect of morphine is peripheral and its antiemetic action is central. In combination, MNTX and morphine may have a clinical role in the treatment of chemotherapy-induced emesis.

Topics: Administration, Oral; Animals; Antiemetics; Antineoplastic Agents; Apomorphine; Cisplatin; Dogs; Drug Interactions; Drug Therapy, Combination; Emetics; Male; Morphine; Naltrexone; Narcotics; Quaternary Ammonium Compounds; Vomiting

Opioids administered to produce analgesia cause unwanted emesis in patients (incidence 20%-30%, depending on situation). Tests in animals show that quaternary narcotic antagonists like methylnaltrexone (MNTX) do not affect the analgesic potency of morphine, but such compounds have not been examined for their potential to antagonize morphine-induced emesis. To determine the effects of MNTX on emetic response, we assigned 85 dogs to one of 11 groups challenged with morphine alone or morphine and various doses of MNTX IM or i.v. Antagonism of the emetic response was dose related: MNTX, 0.25 mg/kg IM or 0.2 mg/kg i.v., completely blocked the emetic effect of morphine in dogs for approximately 60 minutes. If morphine-induced emesis is mediated by receptors available to a quaternary antagonist (perhaps on the peripheral side of the blood-brain barrier), MNTX may prevent opioid-induced emesis. These data indicate that opioid-induced emesis might be prevented without affecting analgesia.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Injections, Intramuscular; Injections, Intravenous; Male; Morphine; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds; Vomiting