Articles: opioid.
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The development of G protein-biased agonists for the μ-opioid receptor (MOR) offers a clear drug discovery rationale for improved analgesia and reduced side-effects of opiate pharmacotherapy. However, our understanding of the molecular mechanisms governing ligand bias is limited, which hinders our ability to rationally design biased compounds. We have investigated the role of MOR binding site residues W320 and Y328 in controlling bias, by receptor mutagenesis. ⋯ We also observe clear uncoupling between mutation-driven changes in function and binding affinity. These findings suggest that the mutations influenced the balance of pathway activation in a ligand-specific manner, thus identifying residues in the MOR binding pocket that govern ligand bias. This increases our understanding of how ligand/receptor binding interactions can be translated into agonist-specific pathway activation.
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Patients with renal colic present to the emergency department in excruciating pain. There is variability in practice regarding the choice of initial analgesic to be used in renal colic. The aim of this article is to outline the protocol for review of the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and paracetamol use in renal colic pain management. ⋯ Formal ethics approval is not required, as primary data will not be collected. We plan to publish the result of this review in a peer-reviewed journal.
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Am J Drug Alcohol Abuse · May 2017
Comparative StudyThe ALERRT® instrument: a quantitative measure of the effort required to compromise prescription opioid abuse-deterrent tablets.
US FDA guidance recommends measuring the degree of effort needed to manipulate abuse-deterrent (AD) opioids. The ALERRT® instrument (PinneyAssociates; Bethesda, MD) uses visual analog scales to assess the labor, effort, and resources necessary to physically compromise AD product candidates in standardized settings. ⋯ Morphine-ADER-IMT was extremely difficult to manipulate versus non-AD formulations of morphine. The ALERRT system differentiated the degree of effort for manipulation of morphine-ADER-IMT and non-AD morphine formulations, indicating sensitivity of this instrument as part of Category 1 testing. By measuring the degree of effort required for manipulation, the ALERRT instrument provides an empirical assessment into the relative difficulty of manipulating opioid analgesics for abuse.
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Pharmacoepidemiol Drug Saf · May 2017
Assessing the accuracy of opioid overdose and poisoning codes in diagnostic information from electronic health records, claims data, and death records.
The purpose of this study is to assess positive predictive value (PPV), relative to medical chart review, of International Classification of Diseases (ICD)-9/10 diagnostic codes for identifying opioid overdoses and poisonings. ⋯ Opioid poisoning codes have a predictive value of 81% to identify opioid overdoses, suggesting ICD opioid poisoning codes can be used to monitor overdose rates and evaluate interventions to reduce overdose. Further research to assess sensitivity, specificity, and negative predictive value are ongoing. Copyright © 2017 John Wiley & Sons, Ltd.