Articles: narcotic-antagonists.
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We previously reported a small series of mixed-efficacy μ opioid receptor (MOR) agonist/δ opioid receptor (DOR) antagonist peptidomimetics featuring a tetrahydroquinoline scaffold and showed the promise of this series as effective analgesics after intraperitoneal administration in mice. We report here an expanded structure-activity relationship study of the pendant region of these compounds and focus in particular on the incorporation of heteroatoms into this side chain. These analogues provide new insight into the binding requirements for this scaffold at MOR, DOR, and the κ opioid receptor (KOR), and several of them (10j, 10k, 10m, and 10n) significantly improve upon the overall MOR agonist/DOR antagonist profile of our previous compounds. In vivo data for 10j, 10k, 10m, and 10n are also reported and show the antinociceptive potency and duration of action of compounds 10j and 10m to be comparable to those of morphine.
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Anesthesia and analgesia · Aug 2015
Predictors of Delayed Postoperative Respiratory Depression Assessed from Naloxone Administration.
The aim of this study was to identify patient and procedural characteristics associated with postoperative respiratory depression or sedation requiring naloxone intervention. ⋯ Obstructive sleep apnea and adverse respiratory events in the recovery room are harbingers of increased risk for respiratory depression or sedation requiring naloxone after discharge from anesthesia care. Also, patients administered naloxone received more opioids and other sedating medications after discharge from anesthetic care. Our findings suggest that these patients may benefit from more careful monitoring after being discharged from anesthesia care.
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Randomized Controlled Trial
A naloxone admixture to prevent opioid-induced pruritus in children: a randomized controlled trial.
Morphine administered by continuous opioid infusion (COI) or by patient-controlled analgesia (PCA) is associated with opioid-induced pruritus (OIP). Intravenous naloxone administered separately to the morphine infusion at a dose of 0.25-1.65 μg·kg(-1)·hr(-1) can provide effective prevention from OIP. Nevertheless, this strategy requires a dedicated intravenous line and an additional infusion pump. The purpose of this study was to determine whether an admixture of naloxone with morphine in normal saline administered via COI or PCA would also prevent OIP in children without attenuation of analgesia or increased opioid utilization. ⋯ This admixture of naloxone and morphine in normal saline did not decrease the incidence or severity of OIP in this sample. Separate administration of naloxone may be the more effective strategy for prevention of OIP. This trial was registered at ClinicalTrials.gov (NCT01071057).