Efficacy of Methylnaltrexone Versus Naloxone for Reversal of Morphine-Induced Depression of Hypoxic Ventilatory Response
| Autor: | Hesham M. Amin, Enrico M. Camporesi, Andrew M. Sopchak, Michael F. Roizen, Joseph F. Foss, B. F. Esposito |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
Male Narcotic Antagonists Analgesic Hypoxic ventilatory response Pharmacology Placebo Naltrexone Bolus (medicine) Double-Blind Method medicine Humans Hypoxia Morphine Naloxone business.industry Narcotic antagonist Respiration Methylnaltrexone Quaternary Ammonium Compounds Anesthesiology and Pain Medicine Anesthesia business medicine.drug |
| Zdroj: | Anesthesia & Analgesia. 78:701 |
| ISSN: | 0003-2999 |
| DOI: | 10.1213/00000539-199404000-00015 |
| Popis: | Methylnaltrexone (MNTX) is a quaternary derivative of naltrexone. It does not cross the blood-brain barrier and, thus, it reverses peripherally mediated effects of morphine without blocking its centrally located analgesic effects. The effects of MNTX on morphine-induced depression of hypoxic ventilatory response are unknown. We evaluated the efficacy of MNTX, compared with naloxone, in reversing this effect. On three sessions separated by a week, 10 healthy male volunteers received morphine, 0.125 mg/kg, as a bolus at 20 min after completing a control hypoxic ventilatory challenge. At 60 min, naloxone, 5 micrograms/kg, MNTX, 0.3 mg/kg, or placebo was administered in a randomized double-blind order. Four isocapnic hypoxic ventilatory challenges were conducted: 0 min (control), 40 min (postmorphine), and 80 and 120 min (postreversal) and the hypoxic respiratory responses were recorded. Morphine administration was associated with a significant depression in hypoxic responses: The slope of the response (L/min/Spo2) and the predicted ventilation at 80% O2 saturation (VE80) (L/min) decreased significantly in the three sessions (P < 0.05). Naloxone injection reversed the respiratory depression at 80 min (85% of the control value of the slope and 89% of VE80), whereas MNTX and placebo did not. At 120 min, the slope (69%) and VE80 (80%) after naloxone administration were not significantly different from control. MNTX slope (69%) was not statistically different from the control, whereas VE80 (70%) was still depressed (P < 0.05). Placebo slope and VE80, at 120 min, remained lower than the control (P < 0.05). These data show that MNTX is not as effective as naloxone for reversal of morphine-mediated depression of respiration during acute hypoxia. |
| Databáze: | OpenAIRE |
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