methylnaltrexone and Pruritus

Published reports on placebo-controlled clinical trials and other studies investigating the use of pure opioid antagonists for the prevention and treatment of opioid-induced pruritus (OIP) were evaluated.. OIP is a common adverse effect of therapeutic use of opioid medications that can have a major impact on patients' comfort, quality of life, and willingness to continue opioid therapy. A literature search identified more than a dozen published reports on the use of pure opioid antagonists (naloxone, naltrexone, methylnaltrexone) for the management of OIP in pediatric and adult patients. Of the studies included in this review, most investigated the effects of naloxone administered by various parenteral routes for the prevention of OIP. Some of those studies indicated a significant reduction in the frequency or severity of pruritus with use of naloxone (a low-dose, continuous i.v. infusion of naloxone appeared to be the most effective treatment). A significant diminution of analgesia requiring increased cumulative doses of morphine was also observed in some studies. A number of studies evaluating the use of orally administered naltrexone for the management of OIP yielded generally less favorable results. Evidence from one small study suggested a potential role for orally administered methylnaltrexone in the prevention of OIP.. Based on the existing data, a low-dose, continuous i.v. infusion of naloxone has the largest body of evidence supporting its use for prevention of OIP in adult and pediatric patients.

Topics: Adult; Analgesics, Opioid; Child; Humans; Infusions, Intravenous; Naloxone; Naltrexone; Narcotic Antagonists; Pruritus; Quality of Life; Quaternary Ammonium Compounds

To describe the role of opioid antagonists in the treatment of opioid-induced constipation and pruritus.. A MEDLINE search was performed (1966-February 2000) for narcotics and opioid antagonists. Results were limited to English-language and clinical trials. Background information was obtained from pharmacology and pharmacotherapy references and review articles. Hand searching of selected bibliographies yielded several references.. Studies were reviewed that examined the use of naloxone, naltrexone, and methylnaltrexone for opioid-related constipation and pruritus. Selected citations included various clinical trials and case series.. Opioid agents are used for cancer and nonmalignant pain. Peripheral opioid receptor stimulation due to endogenous (i.e., endorphins) or exogenous (i.e., morphine) stimulants may result in negative adverse effects, including constipation and pruritus. Adjuvant agents, such as laxatives and antihistamines, are often used to treat these adverse effects, but are themselves associated with adverse effects and are sometimes ineffective. Opioid antagonists have demonstrated reversal of peripheral opioid receptor stimulation. Clinical trials show adequate maintenance of pain control, as well as decreases in opioid-induced constipation and pruritus.. Opioid antagonists offer a therapeutic alternative to conventional adjuvant agents, with the risk of loss of analgesia at higher doses. Methylnaltrexone offers the advantage of peripheral action only, therefore not reversing analgesia. Results are promising; however, larger clinical trials are necessary before opioid antagonists become the standard of care for opioid-induced constipation and pruritus.

Topics: Clinical Trials as Topic; Constipation; Humans; Morphine; Naloxone; Naltrexone; Narcotic Antagonists; Narcotics; Pruritus; Quaternary Ammonium Compounds

Intrathecal morphine-induced pruritus is a very common side-effect that is difficult to prevent or treat. Central and peripheral mechanisms are believed to be involved. The aim of this study was to determine if a peripherally acting, μ-opioid antagonist would reduce morphine-induced pruritus.. We conducted a multicentre, randomized, blinded, placebo-controlled trial of women having elective Caesarean section under spinal anaesthesia with intrathecal morphine 100 μg. After delivery, participants received either subcutaneous methylnatrexone bromide 12 mg (MNTX group, n=69) or saline (placebo group, n=68). Pruritus, nausea, pain, analgesic use, and side-effects were assessed at 2, 4, 8, and 24 h. The primary outcome was the severity of pruritus (0-10 score).. One hundred and thirty-seven women completed the study, with five major protocol violations. There was no statistically significant difference between the MNTX and placebo groups for the median (IQR) pruritus AUC scores [24 (9-47) vs 36 (11-68), median difference 8.5, 95% confidence interval (CI) 0-20, P=0.09] or the worst pruritus score [3 (2-7) vs 5 (2-6), median difference 1, 95% CI 0-2, P=0.24]. The incidence of pruritus was 84% in the MNTX group and 88% in the placebo group (P=0.48). Analgesic and gastrointestinal outcomes did not significantly differ between the groups.. A single dose of subcutaneous methylnaltrexone bromide 12 mg did not reduce the overall severity or incidence of pruritus. In this study, treatment with a peripherally acting μ-opioid antagonist was generally ineffective against intrathecal morphine-induced pruritus, but a small clinical effect cannot be excluded.. Australian New Zealand Clinical Trials Registry (ACTRN12611000345987).

Topics: Adult; Analgesia, Obstetrical; Analgesics, Opioid; Anesthesia, Spinal; Australia; Cesarean Section; Female; Humans; Middle Aged; Morphine; Naltrexone; Narcotic Antagonists; Postoperative Complications; Pregnancy; Pruritus; Quaternary Ammonium Compounds; Singapore; Treatment Outcome; United States; Young Adult

Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter in itch and impaired serotonin signaling has been linked to a variety of itch conditions. Intradermal injection of 5-HT induces scratching behavior in mice through stimulation of 5-HT receptors. Previous studies have demonstrated that selective 5-HT1B/1D receptors agonists, including sumatriptan, inhibits neurotransmission. We have also reported that sumatriptan suppresses chloroquine-induced itch. Therefore, we investigated if sumatriptan has inhibitory effects on serotonin-induced itch in mice. Here, we show that intradermal and intraperitoneal administration of sumatriptan significantly reduce 5-HT-induced scratching behavior in mice. While intradermal injection of GR-127935, a selective 5-HT1B/1D receptors antagonist, reverses the anti-pruritic effects of sumatriptan. In addition, we show that intradermal and intraperitoneal naltrexone (NTX), a non-specific opioid receptor antagonist, and methylnaltrexone (MNTX), a peripherally acting opioid receptor antagonist, significantly decrease the 5-HT-induced scratching behavior. Additionally, combined treatment with sub-effective doses of sumatriptan and an opioid receptor antagonist, naltrexone, decreases 5-HT-evoked scratching responses. We conclude that sumatriptan inhibits 5-HT-induced itch by activating the peripheral 5-HT1B/1D receptors. Moreover, peripheral opioid receptors have a role in serotonin-induced itch, and anti-pruritic effects of sumatriptan seem to involve the opioid system. These data suggest that 5-HT1B/1D receptors agonists maybe useful to treat a variety of pathologic itch conditions with impaired serotonergic system.

Topics: Animals; Disease Models, Animal; Drug Therapy, Combination; Humans; Injections, Intradermal; Male; Mice; Naltrexone; Narcotic Antagonists; Opioid Peptides; Oxadiazoles; Piperazines; Pruritus; Quaternary Ammonium Compounds; Receptors, Serotonin, 5-HT1; Serotonin; Serotonin 5-HT1 Receptor Agonists; Serotonin Antagonists; Sumatriptan

Topics: Aged; Carcinoma, Hepatocellular; Fatal Outcome; Female; Gallbladder Neoplasms; Hepatitis C; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Pain Measurement; Pruritus; Quaternary Ammonium Compounds; Terminal Care

Topics: Aged, 80 and over; Cholestasis; Comorbidity; Humans; Male; Naloxone; Naltrexone; Narcotic Antagonists; Pruritus; Quality of Life; Quaternary Ammonium Compounds