Innovations In Clinical Neuroscience

Hot Topics in Pain Management October 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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17 Hot Topics in Pain Management [October 2017] JOURNAL WATCH officials-met-with-trump-before-opioid- crisis-announcement]. 5. Dowell D, Haegerich TM, and Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep 2016;65(No. RR- 1):1–49. doi: mmwr.rr6501e1. 6. White House Commission on Combating Drug Addiction and the Opioid Crisis. Interim Report. Published online 31 July 2017. Accessed online 27 October 2017. [ interim-report.pdf]. 7. Berro M. 2017. White House opioid commission publishes interim report, recommendations. National Council for Behavioral Health. Published online 3 August 2017. Accessed online 27 October 2017. [https://www.thenationalcouncil. org/capitol-connector/2017/08/3493/]. ABUSE-DETERRENT OPIOID FORMULATIONS NKTR-181: a novel mu-opioid analgesic with inherently low abuse potential. Miyazaki T, Choi IY, Rubas W, et al. J Pharmacol Exp Ther 2017 Oct;363(1):104-113. doi:10.1124/ jpet.117.243030. Epub 2017 Aug 4. Summary. Authors discuss in-vitro and in-vivo studies showing that, through the alteration of brain-entry kinetics, a new long-acting, selective mu-opioid agonist NKTR-181 effectively reduces pain with low potential for abuse. * PMID 28778859 Human abuse potential of the new opioid analgesic molecule NKTR-181 compared with oxycodone. Webster L, Henningfield J, Buchhalter AR, et al. Pain Med. 2017 Mar 10. doi:10.1093/pm/pnw344. [Epub ahead of print] Summary. To compare the potential for abuse along with pharmacokinetics, pharmacodynamics, and safety of NKTR- 181 to oxycodone, researchers conducted a randomized, single-center, double-blind, active- and placebo-controlled five-period crossover study with 42 randomized recreational opioid users (mostly young, white, male adults) in an in-patient setting. They found that NKTR-181 had significantly lower drug liking scores compared to oxycodone at all dose levels, and had scores comparable to placebo for all but the highest dose. Authors conclude that the study opioid showed delayed onset of central nervous system effects and significantly lower abuse potential compared to oxycodone in the study group. * PMID 28340145 New developments in managing opioid addiction: impact of a subdermal buprenorphine implant. Itzoe M, Guarnieri M. Drug Des Devel Ther 2017 May 10;11:1429-1437. doi: 10.2147/DDDT.S109331. eCollection 2017. Review. Summary. In this review, authors discuss the current opioid abuse epidemic and consider existing medications and related costs for therapy. They focus on a newly approved implant designed to deliver steady-state levels of buprenorphine over a six-month period (Probuphine). * PMID 28546740; PMCID: PMC5436774 Clinical relevance of the pharmacokinetic characteristics of an abuse-deterrent, extended-release, injection-molded morphine tablet. JM Dayno et al. J Opioid Manag 2017;13(2):111–124. doi: 10.5055/ jom.2017.0375 Summary. Investigators sought to characterize the pharmacokinetics (PK) and in-vitro alcohol dissolution characteristics of extended-release (ER), injection-molded (IM) morphine tablets with abuse-deterrent (AD) features (morphine-ADER-IMT). In-vivo, in-vitro, and in-silico studies were conducted. A randomized, two-cohort study evaluated the bioequivalence of morphine-ADER- IMT (ARYMO® ER, (morphine sulfate 60 mg) to morphine ER (MS Contin® 60mg) and characterized the effect of food on the PK profile of morphine-ADER-IMT. A three-treatment, three-period crossover study assessed the bioequivalence of morphine-ADER-IMT (30 and 2 µ15mg) to morphine ER (30mg). Bioequivalence of morphine-ADER-IMT 60, 30, and 2 µ 15mg and morphine ER was demonstrated to comparable doses of morphine ER. No clinically significant food effect was observed with morphine- ADER-IMT. The researchers concluded that morphine-ADER-IMT (ARYMO® ER), an ER morphine formulation with robust AD features, has a clinical PK profile that is well suited for patients with chronic pain. * PMID 28829526 Long-term morphine delivery via slow release morphine pellets or osmotic pumps: plasma concentration, analgesia, and naloxone-precipitated withdrawal. McLane VD, Bergquist I, Cormier J, et al. Life Sci 2017 Sep 15;185:1-7. doi: 10.1016/j.lfs.2017.07.016. Epub 2017 Jul 16. Summary. In this study, to compare slow-release morphine sulfate pellets to osmotic pumps for delivering morphine, researchers subcutaneously implanted pellets or pumps in adult mice. They found that both delivery systems showed similar symptoms of dependence, but only the pellets showed anti-nociceptive effect. Authors conclude that the delivery mechanisms were similar in dependence potential, but the pellets were significantly better at inhibiting pain sensation. * PMID 28723417; PMCID: PMC5577921 A randomized, double-blind, double- dummy, placebo-controlled, intranasal drug-liking study on a novel abuse- deterrent formulation of morphine – Morphine ARER. Webster LR, Pantaleon C, Shah MS, et al. Pain Med 2017 Jul 1;18(7):1303-1313.

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