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Opioid pharmacology

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https://www.readbyqxmd.com/read/28345745/in-vitro-and-in-vivo-assessment-of-the-abuse-potential-of-pf614-a-novel-bio-md%C3%A2-prodrug-of-oxycodone
#1
D Lynn Kirkpatrick, William K Schmidt, Ricardo Morales, John Cremin, Julie Seroogy, Craig Husfeld, Thomas Jenkins
OBJECTIVE: The need for pain medication which will not lead to abuse is well recognized. Ensysce has designed prodrug analogs of the commonly used pain medications including hydromorphone, oxycodone (OC), hydrocodone, and morphine that limit their use to oral delivery, two of which are in clinical development. This study was undertaken to demonstrate that PF614, an extended-release prodrug of OC, allows the release of OC as designed when delivered orally, yet it resists ex vivo extraction with household chemicals and is pharmacologically inactive when administered by nonoral routes (nasal and parenteral), thereby substantially reducing its intravenous (IV) and intranasal abuse potential...
January 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28341939/the-basic-pharmacology-of-opioids-informs-the-opioid-discourse-about-misuse-and-abuse-a-review
#2
REVIEW
Joseph V Pergolizzi, Jo Ann LeQuang, Garrett K Berger, Robert B Raffa
Morphine and other opioids are widely used to manage moderate to severe acute pain syndromes, such as pain associated with trauma or postoperative pain, and they have been used to manage chronic pain, even chronic nonmalignant pain. However, recent years have seen a renewed recognition of the potential for overuse, misuse, and abuse of opioids. Therefore, prescribing opioids is challenging for healthcare providers in that clinical effectiveness must be balanced against negative outcomes-with the possibility that neither are achieved perfectly...
March 24, 2017: Pain and Therapy
https://www.readbyqxmd.com/read/28341643/pharmacotherapy-for-diabetic-peripheral-neuropathy-pain-and-quality-of-life-a-systematic-review
#3
Julie M Waldfogel, Suzanne Amato Nesbit, Sydney M Dy, Ritu Sharma, Allen Zhang, Lisa M Wilson, Wendy L Bennett, Hsin-Chieh Yeh, Yohalakshmi Chelladurai, Dorianne Feldman, Karen A Robinson
OBJECTIVE: To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life. METHODS: We searched PubMed and Cochrane Database of Systematic Reviews for systematic reviews from 2011 to October 12, 2015, and PubMed, Embase, and the Cochrane Central Register of Controlled Trials for primary studies from January 1, 2013, to May 24, 2016. We searched Clinicaltrials.gov on March 9, 2016. Two reviewers independently evaluated studies for eligibility, serially abstracted data, and independently evaluated risk of bias and graded strength of evidence (SOE)...
March 24, 2017: Neurology
https://www.readbyqxmd.com/read/28337573/neuroimmune-pharmacology-2nd-edition-a-perspective
#4
Harris A Gelbard
It has been almost nine years since the 1st edition of Neuroimmune Pharmacology was published on May 23rd, 2008. The 2nd edition of Neuroimmune Pharmacology by Ikezu and Gendelman (Editors) with Przedborski, Masliah and Cosentino (Associate Editors) manages to fulfill two separate missions: to provide comprehensive, but highly topical access to a rapidly evolving field and to serve as a standalone reference for scientists and clinicians in need of guidance regarding questions pertinent to neuroimmune pharmacology...
March 23, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28336575/pharmacologic-profile-of-naloxegol-a-peripherally-acting-%C3%A2%C2%B5-opioid-receptor-antagonist-for-the-treatment-of-opioid-induced-constipation
#5
Eike Floettmann, Khanh Bui, Mark Sostek, Kemal Payza, Michael Eldon
Opioid-induced constipation (OIC) is a common side effect of opioid pharmacotherapy for the management of pain because opioid agonists bind to µ-opioid receptors in the enteric nervous system (ENS). Naloxegol, a polyethylene glycol derivative of naloxone and a peripherally acting µ-opioid receptor antagonist, targets the physiologic mechanisms that cause OIC. Pharmacologic measures of opioid activity and pharmacokinetic measures of central nervous system (CNS) penetration were employed to characterize the mechanism of action of naloxegol...
March 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28333341/systemic-administration-of-sialorphin-attenuates-experimental-colitis-in-mice-via-interaction-with-mu-and-kappa-opioid-receptors
#6
M Salaga, A Mokrowiecka, D Jacenik, A I Cygankiewicz, E Malecka-Panas, R Kordek, W M Krajewska, M K Sobocinska, E Kamysz, J Fichna
Background and Aims: Pharmacological treatment and/or maintenance of remission in inflammatory bowel disease (IBD) is currently one of the biggest challenges in the field of gastroenterology. Here we aimed to assess the anti-inflammatory effect and the mechanism of action of sialorphin, the natural blocker of the endogenous opioid peptide-degrading enzymes neprilysin (NEP) and aminopeptidase N (APN), in the mouse models of IBD and the changes in the expression of these enzymes in IBD patients...
March 18, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28332123/self-poisoning-suicide-deaths-in-people-with-bipolar-disorder-characterizing-a-subgroup-and-identifying-treatment-patterns
#7
Ayal Schaffer, Lauren M Weinstock, Mark Sinyor, Catherine Reis, Benjamin I Goldstein, Lakshmi N Yatham, Anthony J Levitt
OBJECTIVE: To characterize self-poisoning suicide deaths in BD compared to other suicide decedents. METHODS: Extracted coroner data from all suicide deaths (n = 3319) in Toronto, Canada from 1998 to 2012. Analyses of demographics, clinical history, recent stressors, and suicide details were conducted in 5 subgroups of suicide decedents: BD self-poisoning, BD other methods, non-BD self-poisoning, non-BD other methods, and unipolar depression self-poisoning. Toxicology results for lethal and present substances were also compared between BD and non-BD self-poisoning subgroups as well as between BD and unipolar depression self-poisoning subgroups...
December 2017: International Journal of Bipolar Disorders
https://www.readbyqxmd.com/read/28327378/gender-related-psychopathology-in-opioid-use-disorder-results-from-a-representative-sample-of-italian-addiction-services
#8
Beniamino Leone, Marco Di Nicola, Lorenzo Moccia, Mauro Pettorruso, Luisa De Risio, Giuseppe Nucara, Lorenzo Zamboni, Antonino Callea, Luigi Janiri, Mauro Cibin, Fabio Lugoboni
AIMS: Gender and psychiatric comorbidity seem to influence patients' inter-individual response to Opioid Substitution Treatments (OST) in Opioid Use Disorder (OUD) management. The aim of the study was to assess psychopathological dimensions in an Italian sample of OUD individuals entering a methadone/buprenorphine maintenance program; secondary, we evaluated the possible gender-specific differences within the psychopathological profiles. METHODS: In a cross-sectional study, we recruited 1052 (792 male; 260 female) OUD subjects receiving OST...
March 10, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28326952/latin-american-guidelines-for-cancer-pain-management
#9
Argelia Lara-Solares, Marisol Ahumada Olea, Amparito de Los Ángeles Basantes Pinos, Sara Bistre Cohén, Patricia Bonilla Sierra, Eva Rossina Duarte Juárez, Omar A Símon Escudero, Juan Guillermo Santacruz Escudero, José Alberto Flores Cantisani
Cancer is a major public health issue. Poor pain management has devastating consequences that seriously affect quality of life, diminish functionality and place a huge emotional burden on patients and their relatives. A group of Latin American opinion leaders were invited to participate in a meeting to discuss areas associated with cancer pain. The expert panel reviewed the latest literature to draft region-specific guidelines for effective pain management. The guidelines make recommendations on tailoring treatment to the specific type of pain and provide local physicians with the state-of-the art findings in the field...
March 13, 2017: Pain Management
https://www.readbyqxmd.com/read/28320888/mutual-reinforcement-of-pathophysiological-host-microbe-interactions-in-intestinal-stasis-models
#10
Ketrija Touw, Daina L Ringus, Nathaniel Hubert, Yunwei Wang, Vanessa A Leone, Anuradha Nadimpalli, Betty R Theriault, Yong E Huang, Johnathan D Tune, Paul B Herring, Gianrico Farrugia, Purna C Kashyap, Dionysios A Antonopoulos, Eugene B Chang
Chronic diseases arise when there is mutual reinforcement of pathophysiological processes that cause an aberrant steady state. Such a sequence of events may underlie chronic constipation, which has been associated with dysbiosis of the gut. In this study we hypothesized that assemblage of microbial communities, directed by slow gastrointestinal transit, affects host function in a way that reinforces constipation and further maintains selection on microbial communities. In our study, we used two models - an opioid-induced constipation model in mice, and a humanized mouse model where germ-free mice were colonized with stool from a patient with constipation-predominant irritable bowel syndrome (IBS-C) in humans...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28320337/barriers-and-facilitators-to-use-of-non-pharmacological-treatments-in-chronic-pain
#11
William C Becker, Lindsey Dorflinger, Sara N Edmond, Leila Islam, Alicia A Heapy, Liana Fraenkel
BACKGROUND: Consensus guidelines recommend multi-modal chronic pain treatment with increased uptake of non-pharmacological pain treatment modalities (NPMs). We aimed to identify the barriers and facilitators to uptake of evidence-based NPMs from the perspectives of patients, nurses and primary care providers (PCPs). METHODS: We convened eight separate groups and engaged each in a Nominal Group Technique (NGT) in which participants: (1) created an individual list of barriers (and, in a subsequent round, facilitators) to uptake of NPMs; (2) compiled a group list from the individual lists; and (3) anonymously voted on the top three most important barriers and facilitators...
March 20, 2017: BMC Family Practice
https://www.readbyqxmd.com/read/28320034/variations-in-infant-cyp2b6-genotype-associated-with-the-need-for-pharmacological-treatment-for-neonatal-abstinence-syndrome-in-infants-of-methadone-maintained-opioid-dependent-mothers
#12
Helen Mactier, Poppy McLaughlin, Cheryl Gillis, Michael David Osselton
Background Neonatal abstinence syndrome (NAS) in infants of methadone-maintained opioid-dependent (MMOD) mothers cannot be predicted in individual cases. We investigated whether variation in infant genotype is associated with severity of NAS. Methods This is a pilot observational cohort study of 21 MMOD mothers and their newborns. Infant buccal swabs were obtained soon after delivery, together with a maternal blood sample for the determination of maternal plasma methadone concentration. Genomic variation in five opioid-related genes (ABCB1, COMT, CYP2B6, CYP2D6, and OPRM1) was ascertained from infant buccal swabs and related to need for pharmacological treatment of NAS...
March 20, 2017: American Journal of Perinatology
https://www.readbyqxmd.com/read/28319053/alternatively-spliced-mu-opioid-receptor-c-termini-impact-the-diverse-actions-of-morphine
#13
Jin Xu, Zhigang Lu, Ankita Narayan, Valerie P Le Rouzic, Mingming Xu, Amanda Hunkele, Taylor G Brown, William F Hoefer, Grace C Rossi, Richard C Rice, Arlene Martínez-Rivera, Anjali M Rajadhyaksha, Luca Cartegni, Daniel L Bassoni, Gavril W Pasternak, Ying-Xian Pan
Extensive 3' alternative splicing of the mu opioid receptor gene OPRM1 creates multiple C-terminal splice variants. However, their behavioral relevance remains unknown. The present study generated 3 mutant mouse models with truncated C termini in 2 different mouse strains, C57BL/6J (B6) and 129/SvEv (129). One mouse truncated all C termini downstream of Oprm1 exon 3 (mE3M mice), while the other two selectively truncated C-terminal tails encoded by either exon 4 (mE4M mice) or exon 7 (mE7M mice). Studies of these mice revealed divergent roles for the C termini in morphine-induced behaviors, highlighting the importance of C-terminal variants in complex morphine actions...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28319052/a-tail-of-opioid-receptor-variants
#14
Stephanie Puig, Howard B Gutstein
Opioids are the gold-standard treatment for severe pain. However, potentially life-threatening side effects decrease the safety and effectiveness of these compounds. The addiction liability of these drugs has led to the current epidemic of opioid abuse in the US. Extensive research efforts have focused on trying to dissociate the analgesic properties of opioids from their undesirable side effects. Splice variants of the mu opioid receptor (MOR), which mediates opioid actions, have unique pharmacological properties and anatomic distributions that make them attractive candidates for therapeutic pain relief...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28315595/the-social-logic-of-naloxone-peer-administration-harm-reduction-and-the-transformation-of-social-policy
#15
Rachel Faulkner-Gurstein
This paper examines overdose prevention programs based on peer administration of the opioid antagonist naloxone. The data for this study consist of 40 interviews and participant observation of 10 overdose prevention training sessions at harm reduction agencies in the Bronx, New York, conducted between 2010 and 2012. This paper contends that the social logic of peer administration is as central to the success of overdose prevention as is naloxone's pharmacological potency. Whereas prohibitionist drug policies seek to isolate drug users from the spaces and cultures of drug use, harm reduction strategies like peer-administered naloxone treat the social contexts of drug use as crucial resources for intervention...
March 9, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28315267/pharmacological-modulation-of-the-sigma-1-receptor-and-the-treatment-of-pain
#16
Manuel Merlos, Javier Burgueño, Enrique Portillo-Salido, Carlos Ramón Plata-Salamán, José Miguel Vela
There is a critical need for new analgesics acting through new mechanisms of action, which could increase the efficacy with respect to existing therapies and reduce their unwanted effects. Current preclinical evidence supports the modulatory role of sigma-1 receptors (σ1R) in nociception, mainly based on the pain-attenuated phenotype of σ1R knockout mice and on the antinociceptive effect exerted by σ1R antagonists on pains of different etiologies. σ1R is highly expressed in different pain areas of the CNS and the periphery (particularly dorsal root ganglia), and interacts and modulates the functionality of different receptors and ion channels ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28302509/binding-mode-analyses-of-nap-derivatives-as-mu-opioid-receptor-selective-ligands-through-docking-studies-and-molecular-dynamics-simulation
#17
Huiqun Wang, Saheem A Zaidi, Yan Zhang
Mu opioid receptor selective antagonists are highly desirable because of their utility as pharmacological probes for receptor characterization and functional studies. Furthermore, the mu opioid receptors act as an important target in drug abuse and addiction treatment. Previously, we reported NAP as a novel lead compound with high selectivity and affinity towards the mu opioid receptor. Based on NAP, we have synthesized its derivatives and further characterized their binding affinities and selectivity towards the receptor...
March 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28301219/management-of-comorbid-bipolar-disorder-and-substance-use-disorders
#18
Ihsan M Salloum, Edson Sherwood Brown
BACKGROUND: The comorbidity of substance use disorders (SUDs) in bipolar disorder is among the highest in psychiatric disorders. Evidence-based controlled psychosocial or pharmacological interventions trials, which may guide treatment decisions, have not been systematically reviewed. OBJECTIVE: To present a narrative review of the public health and clinical significance of this condition, including diagnostic and treatment implications, and to evaluate controlled trials conducted to date...
March 16, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28301217/neuromodulation-with-percutaneous-electrical-nerve-field-stimulation-is-associated-with-reduction-in-signs-and-symptoms-of-opioid-withdrawal-a-multisite-retrospective-assessment
#19
Adrian Miranda, Arturo Taca
BACKGROUND: Finding an effective, non-pharmacological approach to treat opioid withdrawal could remove some of the barriers associated with pharmacotherapy. The BRIDGE® is a noninvasive, percutaneous electrical nerve field stimulator developed to target pain. OBJECTIVES: This pilot study aimed to determine (1) the effects of the BRIDGE on withdrawal scores during the induction phase of opioid withdrawal therapy, (2) the percentage of subjects who successfully transitioned to medication assisted therapy (MAT)...
March 16, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28294136/opioid-modulation-of-value-based-decision-making-in-healthy-humans
#20
Marie Eikemo, Guido Biele, Frode Willoch, Lotte Thomsen, Siri Leknes
Modifying behavior to maximize reward is integral to adaptive decision making. In rodents, the μ-opioid receptor (MOR) system encodes motivation and preference for high-value rewards. Yet it remains unclear whether and how human MORs contribute to value-based decision making. We reasoned that if the human MOR system modulates value-based choice, this would be reflected by opposite effects of agonist and antagonist drugs. In a double-blind pharmacological cross-over study, 30 healthy men received morphine (10 mg), placebo and the opioid antagonist naltrexone (50 mg)...
March 15, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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