Articles: opioid-analgesics.
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Dentists prescribe 1 in 10 opioid prescriptions in the U.S. When opioids are necessary, national guidelines recommend the prescription of low-dose opioids for a short duration. This study assesses the appropriate prescribing of opioids by dentists before guideline implementation. ⋯ Between 1 in 4 and 1 in 2 opioids prescribed to adult dental patients are overprescribed. Judicious opioid-prescribing interventions should be tailored to oral health conditions and dentists.
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Oliceridine is a next-generation investigational intravenous opioid that is a G protein-selective agonist at the μ-opioid receptor. The G protein selectivity of this compound results in potent analgesia with substantially reduced recruitment of β-arrestin, a signaling pathway associated with opioid-related adverse events. In randomized, placebo- and active-controlled clinical studies, use of oliceridine for the management of moderate to severe acute pain provided potent analgesic effect superior to that observed with placebo, with lower incidence of adverse events, including respiratory events and gastrointestinal events of nausea and vomiting, compared with morphine. Here, we provide a review of the preclinical and clinical data of intravenous oliceridine, a selective agonist, which has the potential to offer a wider therapeutic window than conventional opioids.
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Binding and signaling kinetics have previously proven important in validation of biased agonism at GPCRs. Here we provide a comprehensive kinetic pharmacological comparison of clinically relevant μ-opioid receptor agonists, including the novel biased agonist oliceridine (TRV130) which is in clinical trial for pain management. We demonstrate that the bias profile observed for the selected agonists is not time-dependent and that agonists with dramatic differences in their binding kinetic properties can display the same degree of bias. ⋯ GRK2 and GRK5 overexpression greatly increased μ-opioid receptor internalization induced by morphine, but only had modest effects on buprenorphine and oliceridine-induced internalization. Overall, our data reveal that the clinically available drug buprenorphine displays a similar pharmacological bias profile in vitro compared to the clinical candidate drug oliceridine and that this bias is independent of binding kinetics suggesting a mechanism driven by receptor-conformations. This article is part of the Special Issue entitled 'New Vistas in Opioid Pharmacology'.
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Prescription opioid related deaths have increased dramatically over the past 17 years. Although emergency physicians (EPs) have not been the primary force behind this rise, previous literature have suggested that EPs could improve their opioid prescribing practices. We designed this study to evaluate the trend in emergency department (ED) opioid prescriptions over time during the US opioid epidemic. ⋯ ED physicians are prescribing less opiates, while increasing the amount of non-narcotic analgesic prescriptions. This may be in response to the literature suggesting that prescription opioids play a large role in the opioids crisis. This decrease in opioid prescriptions did not increase the need for repeat ED visits.