Articles: opioid.
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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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Although alterations in not only the pain sensitivity but also the analgesic effects of opioids have been reported under conditions of stress, the influence of unpredictable chronic mild stress (UCMS) on the antinociceptive effects of opioid analgesics remains to be fully investigated. The present study examined the influence of UCMS on the thermal pain sensitivity and antinociceptive effects of two opioid analgesics, morphine (an agonist of opioid receptors) and tramadol (an agonist of μ-opioid receptor and an inhibitor of both noradrenaline and serotonin transporters). We also examined the effects of pretreatment with maprotiline (a noradrenaline reuptake inhibitor) and escitalopram (a serotonin reuptake inhibitor) on the antinociceptive action of morphine in mice under an UCMS condition. ⋯ We demonstrated that the antinociceptive effect of morphine but not tramadol was reduced in mice that had experienced UCMS. The reduced antinociceptive effect of morphine under the UCMS condition was ameliorated by pretreatment with maprotiline but not escitalopram. These results suggest that the reduced antinociceptive effects of morphine under conditions of chronic stress may be ameliorated by activation of the noradrenergic but not the serotonergic system.
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Observational Study
Dose-response relationship between methadone dose and adherence to antiretroviral therapy among HIV-positive people who use illicit opioids.
For HIV-positive individuals who use illicit opioids, engagement in methadone maintenance therapy (MMT) can contribute to improved HIV treatment outcomes. However, to our knowledge, the role of methadone dosing in adherence to antiretroviral therapy (ART) has not yet been investigated. We sought to examine the relationship between methadone dose and ART adherence among a cohort of people who use illicit opioids. ⋯ Among HIV-positive individuals in methadone maintenance therapy, those receiving higher doses of methadone (≥ 100 mg/day) are more likely to achieve ≥ 95% adherence to antiretroviral therapy than those receiving lower doses.
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Ankle surgery is often done using a tourniquet. Ischemia/reperfusion injury caused by the tourniquet may increase postoperative pain. The study objective was to investigate the amount of opioids given to patients after ankle surgery with and without tourniquet. ⋯ We found an increase in postoperative opioid consumption correlated to tourniquet use. Possible preventive measures with antioxidant treatment to prevent ischemia/reperfusion injury should be investigated.
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Pharmacoepidemiol Drug Saf · Aug 2015
Comparative StudyTrends in opioid prescribing and co-prescribing of sedative hypnotics for acute and chronic musculoskeletal pain: 2001-2010.
Characterize trends in opioid prescribing and co-prescribing of sedative hypnotics at acute and chronic musculoskeletal pain visits from 2001 to 2010. ⋯ Opioid prescribing for acute and chronic musculoskeletal pain increased from 2001 to 2010, plateauing from 2006 to 2010 for chronic pain visits. Co-prescribing of opioids and sedative hypnotics is common and may represent a target for interventions to improve the safety of opioid prescribing.