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https://www.readbyqxmd.com/read/29236495/a-stable-heroin-analog-that-can-serve-as-a-vaccine-hapten-to-induce-antibodies-that-block-the-effects-of-heroin-and-its-metabolites-in-rodents-and-that-cross-react-immunologically-with-related-drugs-of-abuse
#1
Agnieszka Sulima, Rashmi Jalah, Joshua F G Antoline, Oscar B Torres, Gregory H Imler, Jeffrey R Deschamps, Zoltan Beck, Carl R Alving, Arthur E Jacobson, Kenner C Rice, Gary R Matyas
An improved synthesis of a haptenic heroin surrogate 1 (6-AmHap) is reported. The intermediate needed for the preparation of 1 was described in the route in the synthesis of 2 (DiAmHap). A scalable procedure was developed to install the C-3 amido group. Using the Boc protectng group in 18 allowed preparation of 1 in an overall yield of 53% from 4 and eliminated the necessity of preparing the diamide 13. Hapten 1 was conjugated to tetanus toxoid and mixed with liposomes containing monophosphoryl lipid A as an adjuvant...
December 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29224919/assessment-of-tapentadol-api-abuse-liability-with-the-researched-abuse-diversion-and-addiction-related-surveillance-radars-system
#2
Suzanne K Vosburg, S Geoffrey Severtson, Richard C Dart, Theodore J Cicero, Steven P Kurtz, Mark W Parrino, Jody L Green
Tapentadol, a Schedule II opioid with a combination of µ-opioid activity and norepinephrine reuptake inhibition, is used for the management of moderate to severe acute and chronic pain. Its dual-mechanism of action is thought to reduce opioid-related side effects that can complicate pain management. Since approval, tapentadol has been tracked across multiple outcomes suggesting abuse liability, and a pattern of relatively low, although not absent, abuse liability has been found. This retrospective cohort study further details the abuse liability of tapentadol as an Active Pharmaceutical Ingredient (API) when both immediate-release and extended-release formulations were on the market together (4Q2011 to 2Q2016)...
December 7, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29210063/opioid-induced-inhibition-of-the-human-serotonin-and-norepinephrine-transporters-in-vitro-link-to-clinical-reports-of-serotonin-syndrome
#3
Anna Rickli, Evangelia Liakoni, Marius C Hoener, Matthias E Liechti
BACKGROUND AND PURPOSE: Opioids may inhibit the serotonin and norepinephrine transporters (SERT and NET, respectively). NET inhibition may contribute to analgesia, and SERT inhibition or interactions with serotonin receptors may cause serotonergic toxicity. However, the effects of different opioids on the human SERT, NET, and serotonin receptors have not been sufficiently studied. EXPERIMENTAL APPROACH: We determined the potencies of different opioids to inhibit the SERT and NET in vitro using human transporter-transfected cells...
December 6, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29186453/detection-and-quantification-of-codeine-6-glucuronide-hydromorphone-3-glucuronide-oxymorphone-3-glucuronide-morphine-3-glucuronide-and-morphine-6-glucuronide-in-human-hair-from-opioid-users-by-lc-ms-ms
#4
Megan Grabenauer, Nichole D Bynum, Katherine N Moore, Robert M White, John M Mitchell, Eugene D Hayes, Ronald Flegel
Current hair testing methods that rely solely on quantification of parent drug compounds are unable to definitively distinguish between drug use and external contamination. One possible solution to this problem is to confirm the presence of unique drug metabolites that cannot be present through contamination, such as phase II glucuronide conjugates. This work demonstrates for the first time that codeine-6-glucuronide, hydromorphone-3-glucuronide, oxymorphone-3-glucuronide, morphine-3-glucuronide and morphine-6-glucuronide are present at sufficient concentrations to be quantifiable in hair of opioid users and that their concentrations generally increase as the concentrations of the corresponding parent compounds increase...
November 24, 2017: Journal of Analytical Toxicology
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
#5
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/29016905/relative-abuse-of-crush-resistant-prescription-opioid-tablets-via-alternative-oral-modes-of-administration
#6
Stephen F Butler, Ryan A Black, Alison B Fleming
Objective: Some crush-resistant tablet formulations (CRTs) reduce prescription opioid abuse by nonoral routes of administration (ROAs), especially insufflation and injection, while oral abuse increases. Oral abuse involving product manipulation vs swallowing whole for CRTs and comparators was examined. Methods: Abuse by oral modes of administration (e.g., swallowing whole, chewing, dissolving in the mouth), was examined using the ASI-MV, a computerized, clinical interview for adults in substance abuse treatment from January 2009 to March 2015...
July 8, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28891868/bivalent-ligand-that-activates-mu-opioid-receptor-and-antagonizes-mglur5-receptor-reduces-neuropathic-pain-in-mice
#7
Cristina D Peterson, Kelley F Kitto, Eyup Akgün, Mary M Lunzer, Maureen S Riedl, Lucy Vulchanova, George L Wilcox, Philip S Portoghese, Carolyn A Fairbanks
The mu opioid receptor (MOR) and metabotropic glutamate receptor 5 (mGluR5) are well-established pharmacological targets in the management of chronic pain. Both receptors are expressed in the spinal cord. MMG22, a bivalent ligand containing 2 pharmacophores separated by 22 atoms, which simultaneously activates MOR and antagonizes mGluR5, has been shown to produce potent reversal of tactile hypersensitivity in rodent models of lipopolysaccharide (LPS)-and bone cancer-induced chronic pain. This study assessed whether intrathecal MMG22 also is effective in reducing pain of neuropathic origin...
December 2017: Pain
https://www.readbyqxmd.com/read/28864212/14-o-methylmorphine-a-novel-selective-mu-opioid-receptor-agonist-with-high-efficacy-and-affinity
#8
Ferenc Zádor, Mihály Balogh, András Váradi, Zoltán S Zádori, Kornél Király, Edina Szűcs, Bence Varga, Bernadette Lázár, Sándor Hosztafi, Pál Riba, Sándor Benyhe, Susanna Fürst, Mahmoud Al-Khrasani
14-O-methyl (14-O-Me) group in morphine-6-O-sulfate (M6SU) or oxymorphone has been reported to be essential for enhanced affinity, potency and antinociceptive effect of these opioids. Herein we report on the pharmacological properties (potency, affinity and efficacy) of the new compound, 14-O-methylmorphine (14-O-MeM) in in vitro. Additionally, we also investigated the antinociceptive effect of the novel compound, as well as its inhibitory action on gastrointestinal transit in in vivo. The potency and efficacy of test compound were measured by [(35)S]GTPγS binding, isolated mouse vas deferens (MVD) and rat vas deferens (RVD) assays...
November 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28858693/trends-in-average-days-supply-of-opioid-medications-in-medicaid-and-commercial-insurance
#9
Ali Bonakdar Tehrani, Rachel Mosher Henke, Mir M Ali, Ryan Mutter, Tami L Mark
OBJECTIVES: To calculate trends in adult average days' supply for six commonly prescribed opioids: hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone, and tapentadol to assess whether physicians changed prescribing practices at the time of the intensifying epidemic. METHODS: We used 2005-2015 Truven Health MarketScan Commercial Claims and Encounters data to measure trends in opioid average days' supply among commercially insured individuals and 2005-2014 MarketScan Multi-State Medicaid data to measure trends in opioid average days' supply among Medicaid beneficiaries...
January 2018: Addictive Behaviors
https://www.readbyqxmd.com/read/28814158/a-phase-i-study-of-the-pharmacokinetics-safety-and-tolerability-of-a-novel-tocopheryl-phosphate-mixture-oxymorphone-transdermal-patch-system
#10
Paul D Gavin, Lee S Simon, Thomas Schlagheck, Alisha J Smith, Janakan Krishnarajah
AIM: Characterize the pharmacokinetic profile and tolerability of two tocopheryl phosphate mixture/oxymorphone patch formulations in healthy subjects, and the active metabolite (6-OH-oxymorphone). MATERIALS & METHODS: Fifteen participants received a single application of oxymorphone patches +/- capsaicin for 72 h and were crossed-over for another 72 h. RESULTS: Plasma oxymorphone was detected approximately 7 h and 6-OH-oxymorphone after approximately 18-19 h postapplication of both formulations, respectively...
August 17, 2017: Pain Management
https://www.readbyqxmd.com/read/28802086/acute-kidney-injury-is-common-with-intravenous-abuse-of-extended-release-oral-oxymorphone-and-delayed-renal-recovery-rates-are-associated-with-increased-kdigo-staging
#11
Alex K Bonnecaze, Matthew Whitaker Wilson, Ajay Dharod, Alison Fletcher, P J Miller
BACKGROUND: Prescription opioid abuse poses a serious problem in the United States, representing 615 per 100,000 deaths annually. Extended-release oxymorphone (Opana-ER) is an oral opioid pain medication that has recently been found to cause thrombotic microangiopathy when intravenously abused. In this retrospective study, prevalence and outcomes of AKI among patients intravenously abusing extended-release oral oxymorphone were analyzed. METHODS: A query of electronic medical records for "drug abuse" at an academic medical center during January 2012 to December 2015 was performed and yielded 2350 patients...
August 12, 2017: Nephrology
https://www.readbyqxmd.com/read/28791598/opioid-medications-in-the-management-of-chronic-abdominal-pain
#12
REVIEW
Dajie Wang
PURPOSE OF REVIEW: Chronic abdominal pain is a complex medical condition. The causes of chronic abdominal pain are extremely diverse ranging from chronic pancreatitis, Crohn's disease, to chronic pain with no clear etiology. Treatment of chronic abdominal pain remains a challenge in our clinical practice. While current interventions with celiac plexus blocks and pain medications provide some relief for these patients, but these treatments are typically less efficacious and limited by various adverse effects...
August 8, 2017: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/28718268/oxymorphone-induced-thrombotic-microangiopathy-mimicking-atypical-haemolytic-uremic-syndrome
#13
Amibhen Gandhi, Saad Ullah, Shani Kotadia, Samer Nasser
Atypical Haemolytic Uremic Syndrome (aHUS) is a rare life threatening entity characterized by thrombocytopenia, haemolytic anaemia and renal dysfunction. It is a thrombotic microangiopathy related to genetic mutations in the alternate complement pathway and has a distinct pathophysiology which makes it harder to distinguish from other microangiopathies. We present a case of a 25-year-old male patient with history of polysubstance abuse who presented with chest pain and dyspnoea. He admitted to using injectable oxymorphone (Opana) two weeks before presentation...
April 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28716778/thrombotic-microangiopathy-associated-with-intravenous-injection-of-extended-release-oxycodone
#14
Kate J Robson, Danielle Clucas, Robin Filshie, Harshal Nandurkar
We describe the case of a 35-year-old man presenting with thrombotic microangiopathy (TMA) and renal impairment following, as he later disclosed, intravenous injection of oral formulation tamper-resistant extended-release oxycodone hydrochloride (Oxycontin). Recurrent misuse of this agent was associated with relapsing TMA despite treatment with terminal complement inhibitor eculizumab. Cases of TMA have been reported in the USA in association with intravenous misuse of extended-release oxymorphone (Opana ER) after the introduction of a new non-crushable formulation in 2012...
July 17, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28607779/thrombotic-microangiopathy-secondary-to-intravenous-abuse-of-opana%C3%A2-er
#15
Kamia Thakur, Vaibhav Agrawal, Ashley Kass, Lauren M Dimarino, R Patrick Dorion, Joseph Vadakara
Opana ER (oxymorphone) is an opioid drug available throughout the United States, and intravenous abuse of the crushed oral formulation has been associated with drug-induced thrombotic microangiopathy. In this abstract, we describe two young patients who lived together and used Opana ER intravenously. Both presented with microangiopathic hemolytic anemia that mimicked thrombotic thrombocytopenic purpura (TTP). Treating this condition poses a clinical challenge, as it is difficult to distinguish it from TTP. The role for plasma exchange is not clear but can be used while awaiting the results of the ADAMTS-13 activity, but ultimately supportive care with drug discontinuation is the recommended therapy of choice...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28580158/opana-induced-thrombotic-microangiopathy-masquerading-as-thrombotic-thrombocytopenic-purpura
#16
Byung H Ban, Ashish Verma, Maria Tudor, Jigme Sethi
Opana (oxymorphone) is a powerful semi-synthetic opioid agonist used for chronic pain management that is ingested orally. However, improper injection of Opana can lead to a rare and fatal blood disorder known as thrombotic microangiopathy. Opana-induced thrombotic microangiopathy can be easily mistaken for thrombotic thrombocytopenic purpura (TTP), leading to the initiation of therapeutic plasma exchange. Current literature has conflicting views on the necessity of therapeutic plasma exchange for the treatment of Opana-induced thrombotic microangiopathy...
June 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/28526155/ketorolac-oxymorphone-tapentadol-and-tramadol-a-comprehensive-review
#17
REVIEW
Nalini Vadivelu, Daniel Chang, Erik M Helander, Gregory J Bordelon, Alice Kai, Alan D Kaye, Dora Hsu, Daniel Bang, Inderjeet Julka
Pain remains a tremendous burden on patients and for the health care system, with uncontrolled pain being the leading cause of disability in this country. There are a variety of medications that can be used in the treatment of pain, including ketorolac, oxymorphone, tapentadol, and tramadol. Depending on the clinical situation, these drugs can be used as monotherapy or in conjunction with other types of medications in a multimodal approach. A strong appreciation of pharmacologic properties of these agents and potential side effects is warranted for clinicians...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28481682/acute-impairing-effects-of-morphine-related-to-driving-a-systematic-review-of-experimental-studies-to-define-blood-morphine-concentrations-related-to-impairment-in-opioid-na%C3%A3-ve-subjects
#18
Maren Cecilie Strand, Marianne Arnestad, Bente Fjeld, Jørg Mørland
OBJECTIVE: The objective of this study was to look for dose- and concentration-effect relationships in experimental studies on single-dose administration of morphine on traffic-relevant behavioral tests by a systematic literature review and possibly to see whether a dose/concentration could be defined below which few or no tests would be affected. METHODS: Searches for corresponding literature were conducted using MEDLINE, EMBASE, and PsycINFO, throughout March of 2016...
November 17, 2017: Traffic Injury Prevention
https://www.readbyqxmd.com/read/28394703/comparative-analysis-of-opioid-queries-on-erowid-org-an-opportunity-to-advance-harm-reduction
#19
Rachel S Wightman, Jeanmarie Perrone, Fire Erowid, Earth Erowid, Zachary F Meisel, Lewis S Nelson
BACKGROUND: Many individuals who use opioids turn to online resources to gather information on effects, availability, and safety. OBJECTIVE: Describe opioid index page views on Erowid.org to assess trends in public interest in particular opioids. METHODS: Retrospective analysis of Erowid.org site traffic was performed to identify unique average daily visits to opioid pages. All data was normalized to that of visits to the heroin index page...
August 24, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28369523/desomorphine-screening-using-commercial-enzyme-linked-immunosorbent-assays
#20
Jessica Winborn, Sarah Kerrigan
Desomorphine ("Krokodil") is a semi-synthetic opioid that has drawn attention as a recreational drug, particularly in Russia, neighboring former Soviet Republics, Eastern and Central Europe. It has no accepted medicinal uses and is currently a schedule I drug in the United States. In clandestine environments, desomorphine is synthesized from codeine using red phosphorous, hydroiodic acid and gasoline. Residual starting materials in illicit preparations have been associated with severe dermatological effects and extensive tissue necrosis...
June 1, 2017: Journal of Analytical Toxicology
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