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Redesigning opioids may not prevent their fatal side effect

The dark side of opioids’ ability to deaden pain is the risk that they might kill their user. The same brain receptors that blunt pain when drugs such as morphine or oxycodone bind to them can also signal breathing to slow down. It’s this respiratory suppression that causes most overdose deaths.

So scientists have hoped to design opioids that are “biased” toward activating painkilling signals while leaving respiratory signaling alone. (Science, USA, 27.02.2020)

https://www.sciencemag.org/news/2020/02/redesigning-opioids-may-not-prevent-their-fatal-side-effect

Report on a novel emerging class of highly potent benzimidazole NPS opioids: Chemical and in vitro functional characterization of isotonitazene.

Blanckaert P, Cannaert A, Van Uytfanghe K, Hulpia F, Deconinck E, Van Calenbergh S, Stove C.

Drug Test Anal. 2019 Nov 19. doi: 10.1002/dta.2738. 

Abstract

https://www.ncbi.nlm.nih.gov/pubmed/31743619

Carfentanil: a narrative review of its pharmacology and public health concerns.

Leen JLS, Juurlink DN.

Can J Anaesth. 2019 Apr;66(4):414-421. doi: 10.1007/s12630-019-01294-y. Epub 2019 Jan 21. Review. 

https://link.springer.com/article/10.1007%2Fs12630-019-01294-y

Europa. Europa wil beter zicht op gevaarlijke en zeer verslavende synthetische opioïden

Om Europa voor te bereiden op een toename in het aanbod en gebruik van zeer gevaarlijke synthetische opioïden (waaronder fentanyl en fentanyl-achtigen), gaat het Trimbos-instituut de situatie rond deze drugs in kaart brengen. (Trimbos-instituut, Niederlande, 19.02.2020)

https://www.trimbos.nl/actueel/nieuws/bericht/europa-wil-beter-zicht-op-gevaarlijke-en-zeer-verslavende-synthetische-opioiden

Auf dem Weg zu Schmerzmitteln ohne Suchtgefahr: Säurewert am Schmerzherd ist entscheidend

Opioidhaltige Schmerzmittel sind im klinischen Alltag nahezu unverzichtbar, allerdings haben sie starke Nebenwirkungen. Zusätzlich ist es insbesondere in den USA zu massivem Substanzmissbrauch gekommen. Einem Forschungsteam der Charité – Universitätsmedizin Berlin ist jetzt ein wichtiger Schritt hin zu einer neuen Generation von Schmerzmitteln gelungen. Wie die Forschenden im Fachmagazin Scientific Reports* berichten, kommt es bei der Entwicklung neuer Substanzen auf den Säurewert, den pH-Wert, des Schmerzherds an. Denn die Feinabstimmung der Säure-Dissoziations-Konstante, der sogenannte pKa-Wert, eines Opioidmoleküls bestimmt die Gefährlichkeit, darunter das Suchtpotenzial. (Charité – Universitätsmedizin Berlin, 20.02.2020)

https://idw-online.de/de/news731877

pKa of opioid ligands as a discriminating factor for side effects.

Del Vecchio, G., Labuz, D., Temp, J. et al. 

Sci Rep 9, 19344 (2019). doi.org/10.1038/s41598-019-55886-1

https://www.nature.com/articles/s41598-019-55886-1

Schmerztherapie: Wie sich Opioide einsparen lassen

Dtsch Arztebl 2020; 117(8): A-383 / B-334 / C-322

Schenk, Maren

In Deutschland gibt es keine Opioidepidemie wie in den USA. Dennoch sind Experten alarmiert und bemüht, diese Analgetikagruppe nur streng indiziert zu verordnen und Risikofaktoren für einen Missbrauch zu definieren. Vor allem postoperativ lassen sich Opioide reduzieren. 

https://www.aerzteblatt.de/archiv/212689/Schmerztherapie-Wie-sich-Opioide-einsparen-lassen

Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies.

Franchi S, Moschetti G, Amodeo G, Sacerdote P.

Front Immunol. 2019 Dec 12;10:2914. doi: 10.3389/fimmu.2019.02914.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920107/

The Role of Opioid Receptors in Immune System Function.

Eisenstein TK.

Front Immunol. 2019 Dec 20;10:2904. doi: 10.3389/fimmu.2019.02904. eCollection 2019. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934131/

Kanada. New research shows more people knowingly use fentanyl, points to importance of comprehensive response to reduce risks 

Fentanyl use by people who use drugs in B.C. has doubled since 2015, and two-thirds of people are aware they’ve taken it, finds new research from the BC Centre for Disease Control (BCCDC). (British Clombia Centre for Disease Control (BCCDC), 24.01.2020)

http://www.bccdc.ca/about/news-stories/news-releases/2020/new-research-shows-more-people-knowingly-use-fentanyl-points-to-importance-of-comprehensive-response-to-reduce-risks

Fentanyl: The Most Dangerous Illegal Drug in America

Drug overdoses kill more Americans than car crashes, gunshots, or AIDS at its peak. But it's no longer just a crisis of prescription pills or heroin. It's a crisis of fentanyl. Deaths involving it and other synthetic opioids have surged from around 3,000 in 2013 to more than 30,000 in 2018. 

Researchers at RAND recently published the most comprehensive study to date on what's driving the crisis, how it could play out in the future, and what may be done to save more lives. Among their findings: 

Fentanyl is unlike any other drug problem in modern history. It's more useful to think of it as a mass poisoning than as a traditional drug epidemic.

The crisis is likely to get worse. Fentanyl and other synthetic opioids have swept through some parts of the country while leaving others almost untouched. There are signs that's changing.

Confronting the crisis is going to take more than disrupting the supply and getting people into treatment. Innovative, and controversial, responses—such as supervised drug-consumption sites and fentanyl test strips—must be part of the policy discussion. (RAND, USA, 13.01.2020)

https://www.rand.org/blog/rand-review/2020/01/fentanyl-the-most-dangerous-illegal-drug-in-america.html

Misuse of fentanyl and fentanyl analogues 

This report advises government on the number and nature of known fentanyl analogues, risk factors, pharmacology, toxic effects and misuse and associated harms. (Advisory Council on the Misuse of Drugs, UK, 03.01.2020)

https://www.gov.uk/government/publications/misuse-of-fentanyl-and-fentanyl-analogues

Pain sensitivity and analgesic use among 10,486 adults: the Tromsø study.

Samuelsen PJ, Nielsen CS, Wilsgaard T, Stubhaug A, Svendsen K, Eggen AE.

BMC Pharmacol Toxicol. 2017 Jun 9;18(1):45. doi: 10.1186/s40360-017-0149-2.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466805/

Opioid receptor modulation of neural circuits in depression: What can be learned from preclinical data?

Puryear CB, Brooks J, Tan L, Smith K, Li Y, Cunningham J, Todtenkopf MS, Dean RL, Sanchez C.

Neurosci Biobehav Rev. 2019 Dec 9;108:658-678. doi: 10.1016/j.neubiorev.2019.12.007. 

https://www.sciencedirect.com/science/article/pii/S0149763419306323?via%3Dihub

Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50,000 adults in Iran.

Khademi H, Malekzadeh R, Pourshams A, Jafari E, Salahi R, Semnani S, Abaie B, Islami F, Nasseri-Moghaddam S, Etemadi A, Byrnes G, Abnet CC, Dawsey SM, Day NE, Pharoah PD, Boffetta P, Brennan P, Kamangar F.

BMJ. 2012 Apr 17;344:e2502. doi: 10.1136/bmj.e2502.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328545/

Evaluation of dynorphin and kappa-opioid receptor level in the human blood lymphocytes and plasma: Possible role as a biomarker in severe opioid use disorder.

Shahkarami K, Vousooghi N, Golab F, Mohsenzadeh A, Baharvand P, Sadat-Shirazi MS, Babhadi-Ashar N, Shakeri A, Zarrindast MR.

Drug Alcohol Depend. 2019 Dec 1;205:107638. doi: 10.1016/j.drugalcdep.2019.107638. 

Abstract

https://www.ncbi.nlm.nih.gov/pubmed/31710992

Tramadol. 'Safer opioid' has sparked a crisis in vulnerable countries

Reports rolled in with escalating urgency—pills seized by the truckload, pills swallowed by schoolchildren, pills in the pockets of dead terrorists. 

These pills, the world has been told, are safer than the OxyContins, the Vicodins, the fentanyls that have wreaked so much devastation. But now they are the root of what the United Nations named "the other opioid crisis"—an epidemic featured in fewer headlines than the American one, as it rages through the planet's most vulnerable countries. (MedicalXpress, USA, 13.12.2019)

https://medicalxpress.com/news/2019-12-safer-opioid-crisis-vulnerable-countries.html

American College of Emergency Physicians: Opioid Resources 

Every day emergency physicians see the devastating consequences of the opioid epidemic. ACEP is one of the leaders in the battle against this epidemic.

Here are some of the initiative and resources ACEP has developed and continues to work on to empower emergency physicians. (American College of Emergency Physicians, USA, Dezember 2019)

https://www.acep.org/by-medical-focus/mental-health--substance-abuse/opioids/

A Survey of Molecular Imaging of Opioid Receptors.

Cumming P, Marton J, Lilius TO, Olberg DE, Rominger A.

Molecules. 2019 Nov 19;24(22). pii: E4190. doi: 10.3390/molecules24224190. 

https://www.mdpi.com/1420-3049/24/22/4190

The rising crisis of illicit fentanyl use, overdose, and potential therapeutic strategies.

Han Y, Yan W, Zheng Y, Khan MZ, Yuan K, Lu L.

Transl Psychiatry. 2019 Nov 11;9(1):282. doi: 10.1038/s41398-019-0625-0. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848196/

Estimation of the Number of People With Opioid Addiction in Germany.

Kraus L, Seitz NN, Schulte B, Cremer-Schaeffer P, Braun B, Verthein U, Pfeiffer-Gerschel T.

Dtsch Arztebl Int. 2019 Mar 1;116(9):137-143. doi: 10.3238/arztebl.2019.0137.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460011/

An Exploratory Study of Units of Reporting Opium Use in Iran: Implications for Epidemiologic Studies.

Mohebbi E, Kamangar F, Rahimi-Movaghar A, Haghdoost AA, Etemadi A, Amirzadeh S, Najafi F, Shafeie F, Fakhari A, Ghaleban K, Shahid-Sales S, Hosseini ZS, Honarvar MR, Majnooni F, Hadji M, Zendehdel K.

Arch Iran Med. 2019 Oct 1;22(10):541-545.

http://www.aimjournal.ir/Article/aim-8336

Acute severe intoxication with cyclopropylfentanyl, a novel synthetic opioid.

Wilde M, Sommer MJ, Auwärter V, Hermanns-Clausen M.

Toxicol Lett. 2019 Nov 25. pii: S0378-4274(19)30382-0. doi: 10.1016/j.toxlet.2019.11.025. 

Abstract

https://www.ncbi.nlm.nih.gov/pubmed/31778775

Fentanyl assisted treatment: a possible role in the opioid overdose epidemic?

Bardwell G, Wood E, Brar R.

Subst Abuse Treat Prev Policy. 2019 Nov 11;14(1):50. doi: 10.1186/s13011-019-0241-2.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849248/

Discovery of Novel µ-Opioid Receptor Inverse Agonist from a Combinatorial Library of Tetrapeptides through Structure-Based Virtual Screening.

Poli G, Dimmito MP, Mollica A, Zengin G, Benyhe S, Zador F, Stefanucci A.

Molecules. 2019 Oct 27;24(21). pii: E3872. doi: 10.3390/molecules24213872.

https://www.mdpi.com/1420-3049/24/21/3872

USA. Potent Synthetic Opioid - Isotonitazene - Recently Identified in the Midwestern United States

Purpose: The objective of this public announcement is to notify public health and public safety, law enforcement, clinicians, medical examiners and coroners, laboratory personnel, and all other related communities about new information surrounding the emergent synthetic opioid isotonitazene.  (csfre - Redefining Excellence in forensic Sciences, USA, November 2019)

https://www.npsdiscovery.org/wp-content/uploads/2019/11/Public-Alert_Isotonitazene_NPS-Discovery_111919.pdf

What Will the Opioid Crisis Look Like in Five Years?

Few people had ever heard of fentanyl five years ago. By 2018 this synthetic opioid was implicated in more than 30,000 fatal overdoses in the United States. The next stage of the fast-changing opioid crisis may well depend on how the illegal drug markets morph in the years to come. (RAND Corporation, USA, 18.11.2019)

https://www.rand.org/blog/2019/11/what-will-the-opioid-crisis-look-like-in-five-years.html

The fentanyl epidemic in Estonia: opportunities for a comprehensive public health response

Uuskula, Anneli et al.

The Lancet Psychiatry, Volume 6, Issue 12, 985 

https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(19)30436-5/fulltext

Peripherer Opioid-Agonist bessert Juckreiz bei Dialyse-Patienten

New York – Der urämische Pruritus, der die meisten Dialyse-Patienten quält, lässt sich durch Opiate lindern. Ein Opioid-Agonist, der nur die peripheren Kappa-Rezeptoren stimuliert, hat sich in einer Phase-3-Studie im New England Journal of Medicine (2019; doi: 10.1056/NEJMoa1912770) als sicher und effektiv erwiesen. (aerzteblatt.de, 11.11.2019)

https://www.aerzteblatt.de/nachrichten/107333/Peripherer-Opioid-Agonist-bessert-Juckreiz-bei-Dialyse-Patienten

USA. An opioid more deadly than fentanyl found on Seattle streets (Carfentanil)

SEATTLE (KOMO) -- Right in the midst of the opioid crisis, another illicit drug has hit the streets of Seattle. Experts say it's more potent and deadly than other opiods.

The DEA says carfentanil is 10,000 times more potent than morphine and 100 times stronger than fentanyl. It was first detected in Seattle in March. Experts insists its usage is "very rare" in the area, but nonetheless, it's surfaced in the city. (komonews.com, USA, 12.11.2019)

https://komonews.com/news/local/carfentanil-deadly-drug-has-been-detected-in-seattle