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https://www.readbyqxmd.com/read/28356897/novel-molecular-strategies-and-targets-for-opioid-drug-discovery-for-the-treatment-of-chronic-pain
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28035035/analysis-of-u-47700-a-novel-synthetic-opioid-in-human-urine-by-lc-ms-ms-and-lc-qtof
#6
Steven W Fleming, Justin C Cooley, Leonard Johnson, C Clinton Frazee, Kristina Domanski, Kurt Kleinschmidt, Uttam Garg
The illicit drug market has rapidly evolved from synthetic cannabinoids to cathinone derivatives and now a new emerging threat of synthetic opioids. These compounds were mostly developed by pharmaceutical companies during drug discovery. The new psychoactive substances are not routinely covered in drug screening and may go undetected. Recently fentanyl analogous, AH-7921, MT-45 and now U-47700 have been encountered in clinical and forensic casework. U-47700 is gaining popularity on drug user forms as a legal alternative to heroin...
April 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/27979642/severe-carisoprodol-withdrawal-after-a-14-year-addiction-and-acute-overdose
#7
Kathy T Vo, Howard Horng, Craig G Smollin, Neal L Benowitz
BACKGROUND: Carisoprodol, a centrally acting muscle relaxant with a high abuse potential, has barbiturate-like properties at the GABA-A receptor, leading to central nervous system depression and desired effects. Its tolerance and dependence has been previously demonstrated in an animal model, and withdrawal has been described in several recent case reports. Many cases can be effectively managed with a short course of benzodiazepines or antipsychotic agents. However, abrupt cessation in a patient with a history of long-term and high-dose carisoprodol abuse may result in symptoms that are more difficult for providers to treat...
May 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27790356/moderate-hypothermia-and-its-effects-in-reducing-the-applied-dose-of-anesthetics-for-patients-with-opium-dependence-in-cardiac-surgery-a-randomized-controlled-trial
#8
Reza Jalaian Taghadomi, Ebrahim Golmakani, Kambiz Alizadeh, Behrooz Mottahedi, Ali Rahdari, Shima Sheybani
BACKGROUND: An increasing number of patients addicted to opium are experiencing awareness during coronary artery bypass surgery (CABG) as a result of tolerance to anesthetics. OBJECTIVES: This research was primarily intended to determine the potential diminishing effects of moderate hypothermia on anesthetic dosage and recall of anesthesia during the procedure. METHODS: In this double-blind randomized controlled trial, a total of 80 CABG candidates with known addiction to opium were divided into two groups: one normothermic (N) and the other moderately hypothermic (H), both undergoing induction as well as close monitoring from September 2014 to January 2016...
September 2016: Electronic Physician
https://www.readbyqxmd.com/read/27736030/studies-on-the-metabolism-of-the-fentanyl-derived-designer-drug-butyrfentanyl-in-human-in-vitro-liver-preparations-and-authentic-human-samples-using-liquid-chromatography-high-resolution-mass-spectrometry-lc-hrms
#9
Andrea E Steuer, Elena Williner, Sandra N Staeheli, Thomas Kraemer
Increasing numbers of new psychoactive substances (NPS) among them fentanyl derivatives has been reported by the European monitoring centre for drugs and drug addiction (EMCDDA). Butyrfentanyl is a new fentanyl derivative whose potency ratio was found to be seven compared to morphine and 0.13 compared to fentanyl. Several case reports on butyrfentanyl intoxications have been described. Little is known about its pharmacokinetic properties including its metabolism. However, knowledge of metabolism is essential for analytical detection in clinical and forensic toxicology...
October 13, 2016: Drug Testing and Analysis
https://www.readbyqxmd.com/read/27717535/trends-in-major-opioid-analgesic-consumption-in-taiwan-2002-2014
#10
Kai-Hsiang Kang, Li-Fen Kuo, I-Chen Cheng, Chih-Shiuh Chang, Wen-Ing Tsay
BACKGROUND/PURPOSE: According to WHO guideline, the consumption of opioids is an important sign of national progress in cancer pain relief. However, precise data on the consumption of opioid analgesics consumption in Taiwan has not been published. We investigate opioid analgesic consumption in Taiwan between 2002 and 2014 compare the results with those in other countries to see what we could learn about other methods of pain management. To find out the different patterns between Taiwan and other country, improves the quality of pain management...
October 4, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/27715007/dopamine-d3-d2-receptor-antagonist-pf-4363467-attenuates-opioid-drug-seeking-behavior-without-concomitant-d2-side-effects
#11
Travis T Wager, Thomas Chappie, David Horton, Ramalakshmi Y Chandrasekaran, Brian Samas, Elizabeth R Dunn-Sims, Cathleen Hsu, Nawshaba Nawreen, Michelle A Vanase-Frawley, Rebecca E O'Connor, Christopher J Schmidt, Keith Dlugolenski, Nancy C Stratman, Mark J Majchrzak, Bethany L Kormos, David P Nguyen, Aarti Sawant-Basak, Andy N Mead
Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (≥4/6)...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27672340/use-of-preoperative-gabapentin-significantly-reduces-postoperative-opioid-consumption-a-meta-analysis
#12
Sudha Arumugam, Christine Sm Lau, Ronald S Chamberlain
OBJECTIVES: Effective postoperative pain management is crucial in the care of surgical patients. Opioids, which are commonly used in managing postoperative pain, have a potential for tolerance and addiction, along with sedating side effects. Gabapentin's use as a multimodal analgesic regimen to treat neuropathic pain has been documented as having favorable side effects. This meta-analysis examined the use of preoperative gabapentin and its impact on postoperative opioid consumption. MATERIALS AND METHODS: A comprehensive literature search was conducted to identify randomized control trials that evaluated preoperative gabapentin on postoperative opioid consumption...
2016: Journal of Pain Research
https://www.readbyqxmd.com/read/27110524/intrathecal-dexmedetomidine-and-fentanyl-as-adjuvant-to-bupivacaine-on-duration-of-spinal-block-in-addicted-patients
#13
Farhad Safari, Reza Aminnejad, Seyed Amir Mohajerani, Farshad Farivar, Kamran Mottaghi, Hasan Safdari
BACKGROUND: Addicted patients have innate tolerance to local anesthetics in both neuraxial and peripheral blocks. Dexmedetomidine (Dex) is a highly selective α2 adrenergic receptor agonist used as additive to increase quality and duration of peripheral nerve blocks. OBJECTIVES: The current study aimed to compare the effect of dexmedetomidine and fentanyl additives on bupivacaine to prolong the duration of block and minimizing side effects. PATIENTS AND METHODS: Patients were candidates for elective surgery less than three hours of lower abdomen or lower extremities surgeries...
February 2016: Anesthesiology and Pain Medicine
https://www.readbyqxmd.com/read/26996928/analysis-of-the-abuse-and-diversion-of-the-buprenorphine-transdermal-delivery-system
#14
Timothy J Wiegand, Marie-Claire Le Lait, Becki Bucher Bartelson, Richard C Dart, Jody L Green
UNLABELLED: Prescription opioid abuse and diversion are major causes of morbidity and mortality in the United States. The buprenorphine transdermal delivery system (BTDS) is indicated for the treatment of moderate to severe chronic pain and provides a continuous dose of 5, 7.5, 10, 15, or 20 μg/h buprenorphine for 7 days. Quarterly rates of abuse and diversion of BTDS were compared with 4 comparator groups: 1) other buprenorphine products, 2) fentanyl patches, 3) extended-release (ER) opioid tablets/capsules, and 4) ER tramadol...
June 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/26977701/reducing-the-risks-of-relief-the-cdc-opioid-prescribing-guideline
#15
COMMENT
Thomas R Frieden, Debra Houry
Deaths from prescription-opioid overdose have increased dramatically in the United States, quadrupling in the past 15 years. Efforts to improve pain management resulted in quadrupled rates of opioid prescribing, which propelled a tightly correlated epidemic of addiction, overdose, and death from..
April 21, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/26879590/combatting-synthetic-designer-opioids-a-conjugate-vaccine-ablates-lethal-doses-of-fentanyl-class-drugs
#16
Paul T Bremer, Atsushi Kimishima, Joel E Schlosburg, Bin Zhou, Karen C Collins, Kim D Janda
Fentanyl is an addictive prescription opioid that is over 80 times more potent than morphine. The synthetic nature of fentanyl has enabled the creation of dangerous "designer drug" analogues that escape toxicology screening, yet display comparable potency to the parent drug. Alarmingly, a large number of fatalities have been linked to overdose of fentanyl derivatives. Herein, we report an effective immunotherapy for reducing the psychoactive effects of fentanyl class drugs. A single conjugate vaccine was created that elicited high levels of antibodies with cross-reactivity for a wide panel of fentanyl analogues...
March 7, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/26554195/disciplinary-proceedings-against-doctors-who-abuse-controlled-substances
#17
Danuta Mendelson
This study examined 27 reports from disciplinary tribunals throughout Australia (save Tasmania where reports were not accessible) against medical practitioners who abused narcotic analgesics (often combined with other drugs of addiction) between 2010 and 2015. The reports revealed that 12 medical practitioners were in their 40s; five in their 30s; and one person still in their 20s. Although the majority were general practitioners (15 out of 27), other medical specialties were also represented. Self-administered pethidine was the most prevalent opioid (11 out of 27) and was the only drug used alone...
September 2015: Journal of Law and Medicine
https://www.readbyqxmd.com/read/26345111/long-term-usage-of-narcotic-analgesics-by-chronic-intractable-noncancer-pain-patients-in-taiwan-from-2003-to-2012
#18
I-Chen Cheng, Chih-Shiuh Chang, Wen-Ing Tsay
BACKGROUND/PURPOSE: Chronic pain is a common and important medical problem worldwide. Patients with chronic intractable noncancer pain (CINCP) are treated primarily with narcotics. We analyzed the characteristics of patients with CINCP and the pain prescriptions of Taiwan's physicians. METHODS: We enrolled 644 patients from 66 hospitals approved by the Taiwan Food and Drug Administration to use long-term narcotics for CINCP between 2003 and 2012. RESULTS: The majority (61...
September 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/26342726/methadone-use-and-the-risk-of-hypoglycemia-for-inpatients-with-cancer-pain
#19
James H Flory, Alison C Wiesenthal, Howard T Thaler, Lauren Koranteng, Natalie Moryl
CONTEXT: Methadone is an important drug in the management of both cancer-related and non-cancer-related pain and is the main pharmacologic agent used in the treatment of opioid addiction. Unexpected hypoglycemia has been observed in patients receiving methadone, prompting a more detailed investigation. OBJECTIVES: To evaluate the incidence of hypoglycemia in a cohort of inpatients receiving methadone versus other opioids including fentanyl, hydromorphone, and morphine...
January 2016: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/26118001/-non-oncologic-chronic-pain-treatment-with-opiates
#20
Glòria Molas Ferrer, Montse Castellà Kastner, María Lombraña Mencia
Non-oncologic chronic pain is a very common symptom. It causes great impact on daily activities of people who suffer it. The incidence of this type of pain is rising due to the increase in life expectancy. The most affected population is geriatric population. Back pain, osteoarthritic pain and neuropathic pain are the most prevalent types of non-oncologic chronic pain. Opiates, among other analgesic drugs, are used to alleviate this type of pain. Opiates are divided into minor opiates (tramadol, codeine) and major opiates (morphine, fentanyl, oxycodone, methadone)...
September 2014: Revista de Enfermería
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