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https://www.readbyqxmd.com/read/29895890/opioid-receptor-signaling-analgesic-and-side-effects-induced-by-a-computationally-designed-ph-dependent-agonist
#1
Viola Spahn, Giovanna Del Vecchio, Antonio Rodriguez-Gaztelumendi, Julia Temp, Dominika Labuz, Michael Kloner, Marco Reidelbach, Halina Machelska, Marcus Weber, Christoph Stein
Novel pain killers without adverse effects are urgently needed. Opioids induce central and intestinal side effects such as respiratory depression, sedation, addiction, and constipation. We have recently shown that a newly designed agonist with a reduced acid dissociation constant (pKa ) abolished pain by selectively activating peripheral μ-opioid receptors (MOR) in inflamed (acidic) tissues without eliciting side effects. Here, we extended this concept in that pKa reduction to 7.22 was achieved by placing a fluorine atom at the ethylidene bridge in the parental molecule fentanyl...
June 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29708863/addressing-the-growing-opioid-and-heroin-abuse-epidemic-a-call-for-medical-school-curricula
#2
Madison C Ratycz, Thomas J Papadimos, Allison A Vanderbilt
Substance abuse is a growing public health concern in the USA (US), especially now that the US faces a national drug overdose epidemic. Over the past decade, the number of drug overdose deaths has rapidly grown, largely driven by increases in prescription opioid-related overdoses. In recent years, increased heroin and illicitly manufactured fentanyl overdoses have substantially contributed to the rise of overdose deaths. Given the role of physicians in interacting with patients who are at risk for or currently abusing opioids and heroin, it is essential that physicians are aware of this issue and know how to respond...
December 2018: Medical Education Online
https://www.readbyqxmd.com/read/29675893/characteristics-of-opioid-maintained-clients-smoking-fentanyl-patches-the-importance-of-confirmatory-drug-analysis-illustrated-by-a-case-series-and-mini-review
#3
Andreas Kimergård, Jacklyn Dunne, Anette Bøgen, Peter Hindersson, Torben Breindahl
The increase in opioid prescribing in many European countries over the last decade has raised concerns about associated diversion, overdose, and mortality. Fentanyl is one of these synthetic opioids that is typically prescribed as a transdermal patch for pain that requires continuous pain relief and has been the focus of investigation due to reports of overdose and death. We report a case series of 14 drug addiction treatment entrants, who entered treatment in a service located in the region of Southern Denmark from August 2015 to December 2015 for smoking fentanyl patches...
April 19, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29570781/the-president-s-commission-on-combating-drug-addiction-and-the-opioid-crisis-origins-and-recommendations
#4
Bertha K Madras
The United States has the ignominious distinction of leading the world in opioid prescribing,1 and in opioid-related overdose deaths. The Centers for Disease Control (CDC) estimates that over 40,000 people died of an opioid-related overdose, with fentanyl-related deaths exceeding those of heroin or prescription opioids.2 Opioid overdoses are now the leading cause of unintentional deaths in the US and of declining lifespan expectancies.3 With a worsening crisis, agencies of the US government and others produced an array of reports on the opioid crisis...
March 23, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29551331/trends-in-medical-use-of-opioids-in-the-u-s-2006-2016
#5
Brian J Piper, Dipam T Shah, Olapeju M Simoyan, Kenneth L McCall, Stephanie D Nichols
INTRODUCTION: The U.S. is experiencing an opioid epidemic which is at least partially iatrogenic and fueled by both prescription and illicit misuse. This study provides a nationwide examination of opioid distribution patterns during the last decade. METHODS: Data were obtained from the U.S. Drug Enforcement Administration's Automation of Reports and Consolidated Orders System for 2006-2016. Analyses include quantities of ten opioids legally dispensed nationwide by weight and converted to Morphine Milligram Equivalents...
May 2018: American Journal of Preventive Medicine
https://www.readbyqxmd.com/read/29486974/use-of-epidural-clonidine-for-the-management-of-analgesia-in-the-opioid-addicted-parturient-on-buprenorphine-maintenance-therapy-an-observational-study
#6
M R Hoyt, U Shah, J Cooley, M Temple
OBJECTIVES: Management of labor analgesia and post-cesarean delivery pain is challenging in the patient taking buprenorphine as opioid addiction maintenance therapy. We observed whether substituting clonidine for fentanyl in an epidural solution would provide adequate analgesia for labor and after cesarean delivery. METHODS: We substituted our standard 2 µg/mL fentanyl in 0.0625% bupivacaine epidural solution with 2 µg/mL clonidine in 0.0625% bupivacaine, or 1...
May 2018: International Journal of Obstetric Anesthesia
https://www.readbyqxmd.com/read/29474213/the-opioid-epidemic-and-the-current-prevalence-of-substance-use-disorder-in-anesthesiologists
#7
Ethan O Bryson
PURPOSE OF REVIEW: There has been a substantial increase in prescription and illicit opioid abuse in the general population observed over the last two decades. Initially fueled by an influx of prescription opioid medications, the opioid epidemic now includes increasingly potent heroin and illicit fentanyl. Younger anesthesiologists, those currently in training or recent graduates, have come of age in a society where opioid abuse is much more prevalent. RECENT FINDINGS: The current prevalence of substance use disorder (SUD) in the physician population is slightly higher than in the general population and appears to be increasing...
June 2018: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/29459328/risk-of-fentanyl-involved-overdose-among-those-with-past-year-incarceration-findings-from-a-recent-outbreak-in-2014-and-2015
#8
Lauren Brinkley-Rubinstein, Alexandria Macmadu, Brandon D L Marshall, Andrew Heise, Shabbar I Ranapurwala, Josiah D Rich, Traci C Green
Overdose is the leading cause of unintentional injury-related death. Rhode Island (RI) has the highest rate of illicit drug use nationally and the 5th highest overdose mortality rate. RI has experienced an outbreak of fentanyl-related overdoses. In incarcerated populations, risk of overdose is greatly elevated. However, little is known about fentanyl-related overdose post-release. In the current analyses, we identify changes in fentanyl-related fatal overdose among those who died in 2014 and 2015 who were incarcerated in the year before death...
April 1, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29231916/-the-use-of-transdermal-fentanyl-in-the-treatment-of-patients-suffering-from-chronic-non-cancer-pain-case-reports
#9
Tatiana Pietrzyńska, Łukasz Pietrzyński
The use of strong opioids for the treatment of chronic non-cancer pain (CNCP) has gained undisputed acceptance among specialists and should be considered when other pharmacological treatments are not effective or cause serious side effects. However, drugs from the third step of analgesic ladder still raise concerns among doctors and patients in the case of long-term therapy. A CASE REPORT: The authors present reports of three cases of patients with CNCP caused by musculoskeletal disorders and numerous comorbidities...
November 23, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29190175/going-beyond-prescription-pain-relievers-to-understand-the-opioid-epidemic-the-role-of-illicit-fentanyl-new-psychoactive-substances-and-street-heroin
#10
REVIEW
Joseph V Pergolizzi, Jo Ann LeQuang, Robert Taylor, Robert B Raffa
The opioid epidemic is associated with morbidity and mortality, and it has taken a vast toll on American society. While prescription opioid abuse is part of the opioid problem, it is by no means the entirety of it. Opioid abuse appears to have entered a technology-driven new world of clandestine labs all over the globe and many new synthetic analog, counterfeit, and adulterated drugs that arrive via the internet faster than the Drug Enforcement Administration (DEA) can catalog and outlaw them. To deal with opioid abuse, it must be recognized that it is more - far more - than a subset of chronic pain patients who become addicted...
January 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29084357/adverse-events-associated-with-medium-and-long-term-use-of-opioids-for-chronic-non-cancer-pain-an-overview-of-cochrane-reviews
#11
REVIEW
Charl Els, Tanya D Jackson, Diane Kunyk, Vernon G Lappi, Barend Sonnenberg, Reidar Hagtvedt, Sangita Sharma, Fariba Kolahdooz, Sebastian Straube
BACKGROUND: Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for chronic non-cancer pain (CNCP) remains controversial. This overview of Cochrane Reviews complements the overview entitled 'High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews'. OBJECTIVES: To provide an overview of the occurrence and nature of adverse events associated with any opioid agent (any dose, frequency, or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults...
October 30, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28967324/fentanyl-and-the-evolving-opioid-epidemic-what-strategies-should-policy-makers-consider
#12
Colleen L Barry
Major policy efforts are being aimed at combating the epidemic of opioid addiction and overdose deaths. In response to the epidemic, the medical community and policy makers have attempted to intervene; to date, these varied approaches have done little to reverse the increase in mortality related to opioid overdose. One factor that has complicated efforts to control overdose deaths has been the emergence of a public health crisis related to illicit fentanyl. The rise in fentanyl-related overdose deaths means that new approaches are needed to combat the opioid epidemic, including adoption of harm reduction strategies...
January 1, 2018: Psychiatric Services: a Journal of the American Psychiatric Association
https://www.readbyqxmd.com/read/28942032/post-mortem-review-of-fentanyl-related-overdose-deaths-among-identified-drug-users-in-southern-bavaria-germany-2005-2014
#13
Inga Sinicina, Hans Sachs, Wolfgang Keil
BACKGROUND: Two decades ago, there were only single case reports on deaths in Europe following the consumption of illicitly manufactured fentanyl by problem drug users. Today, lethal fentanyl intoxication is now no longer a rarity. Since 2005, a rapid increase of lethal fentanyl-related intoxications in the drug scene has been observed at the Institute of Legal Medicine, Ludwig Maximilians University, Munich. We hypothesized that this rise is the result of the launch of fentanyl matrix patches in Germany in 2004, their broad acceptance, their diversion from the regulated supply chain, and incautious prescription by medical care providers...
September 14, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28910257/between-a-rock-and-a-hard-place-prescription-opioid-restrictions-in-the-time-of-fentanyl-and-other-street-drug-adulterants
#14
Tessa Cheng, Kora DeBeck
Non-medical prescription opioid use (NMPOU) has increased alarmingly across Canada and resulted in strict prescribing restrictions on opioids. Despite a clear need to reduce opioid prescriptions in response to this crisis, few other policies have been implemented and this singular focus is incongruent with the known characteristics of substance use disorders, negative effects of supply reduction policies, and realities of pain management. Given the recent rise of fentanyl and other dangerous adulterants in street drugs, this commentary argues that a comprehensive response to NMPOU that includes improvements to addiction management and harm-reduction services is urgently needed...
September 14, 2017: Canadian Journal of Public Health. Revue Canadienne de Santé Publique
https://www.readbyqxmd.com/read/28713291/an-expanding-world-of-novel-psychoactive-substances-opioids
#15
REVIEW
Jolanta B Zawilska
The abuse of novel psychoactive substances (NPS) has been increasing dramatically worldwide since late 2000s. By the end of 2015, more than 560 NPS had been reported to the European Monitoring Centre for Drugs and Drug Addiction. Although the most popular compounds are synthetic cannabinoids and psychostimulatory derivatives of cathinone (so-called β-keto-amphetamines), novel synthetic opioids have recently emerged on the recreational drug market. They include fentanyl (a potent narcotic analgesic) and its analogs (e...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28356897/novel-molecular-strategies-and-targets-for-opioid-drug-discovery-for-the-treatment-of-chronic-pain
#16
REVIEW
Keith M Olson, Wei Lei, Attila Keresztes, Justin LaVigne, John M Streicher
Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28333316/convergent-balancing-selection-on-the-mu-opioid-receptor-in-primates
#17
Carolyn G Sweeney, Juliette M Rando, Helen N Panas, Gregory M Miller, Donna M Platt, Eric J Vallender
The mu opioid receptor is involved in many natural processes including stress response, pleasure, and pain. Mutations in the gene also have been associated with opiate and alcohol addictions as well as with responsivity to medication targeting these disorders. Two common and mutually exclusive polymorphisms have been identified in humans, A118G (N40D), found commonly in non-African populations, and C17T (V6A), found almost exclusively in African populations. Although A118G has been studied extensively for associations and in functional assays, C17T is much less well understood...
July 1, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28254944/a-nontoxic-pain-killer-designed-by-modeling-of-pathological-receptor-conformations
#18
V Spahn, G Del Vecchio, D Labuz, A Rodriguez-Gaztelumendi, N Massaly, J Temp, V Durmaz, P Sabri, M Reidelbach, H Machelska, M Weber, C Stein
Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation...
March 3, 2017: Science
https://www.readbyqxmd.com/read/28213891/opioids-and-the-immune-system-friend-or-foe
#19
REVIEW
Lisanne Mirja Plein, Heike L Rittner
Systemically administered opioids are among the most powerful analgesics for treating severe pain. Several negative side effects (respiratory depression, addiction, nausea and confusion) and the risk of opioid-induced hyperalgesia accompany opioid administration. One other side effect is the potential of opioids to suppress the immune response and thereby to increase the vulnerability to infections. The link between opioids and immunosuppression has been investigated both in vitro and in vivo as well as in patients...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28074831/rgs9-2-modulates-responses-to-oxycodone-in-pain-free-and-chronic-pain-states
#20
Sevasti Gaspari, Valeria Cogliani, Lefteris Manouras, Ethan M Anderson, Vasiliki Mitsi, Kleopatra Avrampou, Fiona B Carr, Venetia Zachariou
Regulator of G-protein signaling 9-2 (RGS9-2) is a striatal-enriched signal-transduction modulator known to have a critical role in the development of addiction-related behaviors following exposure to psychostimulants or opioids. RGS9-2 controls the function of several G-protein-coupled receptors, including dopamine receptor and mu opioid receptor (MOR). We previously showed that RGS9-2 complexes negatively control morphine analgesia, and promote the development of morphine tolerance. In contrast, RGS9-2 positively modulates the actions of other opioid analgesics, such as fentanyl and methadone...
June 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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