Opioid-induced delay in gastric emptying: a peripheral mechanism in humans.

Hdl Handle:
http://hdl.handle.net/10147/209203
Title:
Opioid-induced delay in gastric emptying: a peripheral mechanism in humans.
Authors:
Murphy, D B; Sutton, J A; Prescott, L F; Murphy, M B
Affiliation:
Cork University Hospital, Wilton, Cork City, Ireland.
Citation:
Anesthesiology. 1997 Oct;87(4):765-70.
Journal:
Anesthesiology
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209203
PubMed ID:
9357876
Abstract:
BACKGROUND: Opioids delay gastric emptying, which in turn may increase the risk of vomiting and pulmonary aspiration. Naloxone reverses this opiate action on gastric emptying, but it is not known whether this effect in humans is mediated by central or peripheral opiate antagonism. The importance of peripheral opioid receptor antagonism in modulating opioid-induced delay in gastric emptying was evaluated using methylnaltrexone, a quaternary derivative of the opiate antagonist naltrexone, which does not cross the blood-brain barrier. METHODS: In a randomized, double-blind, crossover placebo-controlled study, 11 healthy volunteers were given either placebo (saline), 0.09 mg/kg morphine, or 0.09 mg/kg morphine plus 0.3 mg/kg methylnaltrexone on three separate occasions before ingesting 500 ml deionized water. The rate of gastric emptying was measured by two methods: a noninvasive epigastric bioimpedance technique and the acetaminophen absorption test. RESULTS: The epigastric bioimpedance technique was sufficiently sensitive to detect opioid-induced changes in the rate of gastric emptying. The mean +/- SD time taken for the gastric volume to decrease to 50% (t0.5) after placebo was 5.5 +/- 2.1 min. Morphine prolonged gastric emptying to (t0.5) of 21 +/- 9.0 min (P < 0.03). Methylnaltrexone given concomitantly with morphine reversed the morphine-induced delay in gastric emptying to a t0.5 of 7.4 +/- 3.0 (P < 0.04). Maximum concentrations and area under the concentration curve from 0 to 90 min of serum acetaminophen concentrations after morphine were significantly different from placebo and morphine administered concomitantly with methylnaltrexone (P < 0.05). No difference in maximum concentration or area under the concentration curve from 0 to 90 min was noted between placebo and methylnaltrexone coadministered with morphine. CONCLUSIONS: The attenuation of morphine-induced delay in gastric emptying by methylnaltrexone suggests that the opioid effect is mediated outside the central nervous system. Methylnaltrexone may have the potential to decrease the side effects of opioid medications, which are mediated peripherally, while maintaining the central analgesia effect of the opioid.
Language:
eng
MeSH:
Acetaminophen/blood; Adult; Cross-Over Studies; Double-Blind Method; Female; Gastric Emptying/*drug effects; Humans; Male; Naltrexone/*analogs & derivatives/pharmacology; Narcotic Antagonists/*pharmacology; Narcotics/*adverse effects; Quaternary Ammonium Compounds
ISSN:
0003-3022 (Print); 0003-3022 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMurphy, D Ben_GB
dc.contributor.authorSutton, J Aen_GB
dc.contributor.authorPrescott, L Fen_GB
dc.contributor.authorMurphy, M Ben_GB
dc.date.accessioned2012-02-03T15:14:58Z-
dc.date.available2012-02-03T15:14:58Z-
dc.date.issued2012-02-03T15:14:58Z-
dc.identifier.citationAnesthesiology. 1997 Oct;87(4):765-70.en_GB
dc.identifier.issn0003-3022 (Print)en_GB
dc.identifier.issn0003-3022 (Linking)en_GB
dc.identifier.pmid9357876en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209203-
dc.description.abstractBACKGROUND: Opioids delay gastric emptying, which in turn may increase the risk of vomiting and pulmonary aspiration. Naloxone reverses this opiate action on gastric emptying, but it is not known whether this effect in humans is mediated by central or peripheral opiate antagonism. The importance of peripheral opioid receptor antagonism in modulating opioid-induced delay in gastric emptying was evaluated using methylnaltrexone, a quaternary derivative of the opiate antagonist naltrexone, which does not cross the blood-brain barrier. METHODS: In a randomized, double-blind, crossover placebo-controlled study, 11 healthy volunteers were given either placebo (saline), 0.09 mg/kg morphine, or 0.09 mg/kg morphine plus 0.3 mg/kg methylnaltrexone on three separate occasions before ingesting 500 ml deionized water. The rate of gastric emptying was measured by two methods: a noninvasive epigastric bioimpedance technique and the acetaminophen absorption test. RESULTS: The epigastric bioimpedance technique was sufficiently sensitive to detect opioid-induced changes in the rate of gastric emptying. The mean +/- SD time taken for the gastric volume to decrease to 50% (t0.5) after placebo was 5.5 +/- 2.1 min. Morphine prolonged gastric emptying to (t0.5) of 21 +/- 9.0 min (P < 0.03). Methylnaltrexone given concomitantly with morphine reversed the morphine-induced delay in gastric emptying to a t0.5 of 7.4 +/- 3.0 (P < 0.04). Maximum concentrations and area under the concentration curve from 0 to 90 min of serum acetaminophen concentrations after morphine were significantly different from placebo and morphine administered concomitantly with methylnaltrexone (P < 0.05). No difference in maximum concentration or area under the concentration curve from 0 to 90 min was noted between placebo and methylnaltrexone coadministered with morphine. CONCLUSIONS: The attenuation of morphine-induced delay in gastric emptying by methylnaltrexone suggests that the opioid effect is mediated outside the central nervous system. Methylnaltrexone may have the potential to decrease the side effects of opioid medications, which are mediated peripherally, while maintaining the central analgesia effect of the opioid.en_GB
dc.language.isoengen_GB
dc.subject.meshAcetaminophen/blooden_GB
dc.subject.meshAdulten_GB
dc.subject.meshCross-Over Studiesen_GB
dc.subject.meshDouble-Blind Methoden_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGastric Emptying/*drug effectsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshNaltrexone/*analogs & derivatives/pharmacologyen_GB
dc.subject.meshNarcotic Antagonists/*pharmacologyen_GB
dc.subject.meshNarcotics/*adverse effectsen_GB
dc.subject.meshQuaternary Ammonium Compoundsen_GB
dc.titleOpioid-induced delay in gastric emptying: a peripheral mechanism in humans.en_GB
dc.contributor.departmentCork University Hospital, Wilton, Cork City, Ireland.en_GB
dc.identifier.journalAnesthesiologyen_GB
dc.description.provinceMunster-

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