Clustering Patterns in Polysubstance Mortality in the United States in 2017: A Multiple Correspondence Analysis of Death Certificate Data
CONCLUSION: While individual drug substances might contribute to many deaths (e.g., fentanyl), polysubstance mortality is more common than single substance mortality. Multidimensional analyses integrating all drugs involved are useful to identify uncommon patterns of overdose and changing trends.PMID:35378292 | DOI:10.1016/j.annepidem.2022.03.011 (Source: Annals of Epidemiology)
Source: Annals of Epidemiology - April 4, 2022 Category: Epidemiology Authors: Joshua C Black Karilynn M Rockhill Richard C Dart Janetta Iwanicki Source Type: research
Clustering Patterns in Polysubstance Mortality in the United States in 2017: A Multiple Correspondence Analysis of Death Certificate Data
CONCLUSION: While individual drug substances might contribute to many deaths (e.g., fentanyl), polysubstance mortality is more common than single substance mortality. Multidimensional analyses integrating all drugs involved are useful to identify uncommon patterns of overdose and changing trends.PMID:35378292 | DOI:10.1016/j.annepidem.2022.03.011 (Source: Annals of Epidemiology)
Source: Annals of Epidemiology - April 4, 2022 Category: Epidemiology Authors: Joshua C Black Karilynn M Rockhill Richard C Dart Janetta Iwanicki Source Type: research
Clustering Patterns in Polysubstance Mortality in the United States in 2017: A Multiple Correspondence Analysis of Death Certificate Data
CONCLUSION: While individual drug substances might contribute to many deaths (e.g., fentanyl), polysubstance mortality is more common than single substance mortality. Multidimensional analyses integrating all drugs involved are useful to identify uncommon patterns of overdose and changing trends.PMID:35378292 | DOI:10.1016/j.annepidem.2022.03.011 (Source: Annals of Epidemiology)
Source: Annals of Epidemiology - April 4, 2022 Category: Epidemiology Authors: Joshua C Black Karilynn M Rockhill Richard C Dart Janetta Iwanicki Source Type: research
GSE198375 RNA Expression in the left lateral lobe of the liver in BALB/cJ and BALB/cByJ substrains of mice to identify candidate mechanisms for Oxycodone QTLs
Contributors : Jacob A Beierle ; Camron D BryantSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe found BALB/cByJ and BALB/cJ mice differ in their responses to oxycodone state dependent conditioned place preference, whole brain [oxycodone] and its metabolites [noroxycodone] and [oxymorphone] following oxycodone administration, the 53.5 °C hot plate, mechanical stimulation in the von Frey test, and gross brain weight. We then identified a quantitative trait locus (QTL) on chromosome 15 for whole brain [Oxymorphone] (LOD = 7.07; p< 0.001), 13 for hot plate sensitivity (LOD = 10.7; p< ...
Source: GEO: Gene Expression Omnibus - March 14, 2022 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
GSE196352 RNA Expression QTL mapping in Striatum of an F2 cross of BALB/cJ and BALB/cByJ mice to identify candidate genes for behavioral/metabolic QTLs
Contributors : Jacob A Beierle ; Camron D BryantSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe found BALB/cByJ and BALB/cJ mice differ in their responses to oxycodone state dependent conditioned place preference, whole brain [oxycodone] and its metabolites [noroxycodone] and [oxymorphone] following oxycodone administration, the 53.5 °C hot plate, mechanical stimulation in the von Frey test, and gross brain weight. We then identified a quantitative trait locus (QTL) on chromosome 15 for whole brain (LOD = 7.07; p< 0.001), 13 for hot plate sensitivity (LOD = 10.7; p< 0.001; peak = ...
Source: GEO: Gene Expression Omnibus - February 11, 2022 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
GSE196334 RNA Expression QTL mapping in an F2 cross of BALB/cJ and BALB/cByJ mice to identify candidate genes for behavioral/metabolic QTLs
Contributors : Jacob A Beierle ; Camron D BryantSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe found BALB/cByJ and BALB/cJ mice differ in their responses to oxycodone state dependent conditioned place preference, whole brain [oxycodone] and its metabolites [noroxycodone] and [oxymorphone] following oxycodone administration, the 53.5 °C hot plate, mechanical stimulation in the von Frey test, and gross brain weight. We then identified a quantitative trait locus (QTL) on chromosome 15 for whole brain (LOD = 7.07; p< 0.001), 13 for hot plate sensitivity (LOD = 10.7; p< 0.001; peak = ...
Source: GEO: Gene Expression Omnibus - February 11, 2022 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Sex, estrous cycle, and hormone regulation of CYP2D in the brain alters oxycodone metabolism and analgesia
Biochem Pharmacol. 2022 Feb 7:114949. doi: 10.1016/j.bcp.2022.114949. Online ahead of print.ABSTRACTOpioids, and numerous centrally active drugs, are metabolized by cytochrome P450 2D (CYP2D). There are sex and estrous cycle differences in brain oxycodone analgesia. Here we investigated the mechanism examining the selective role of CYP2D in the brain on sex, estrous cycle, and hormonal regulation. Propranolol, CYP2D-specific mechanism-based inhibitor, or vehicle was delivered into cerebral ventricles 24 hours before administering oxycodone (or oxymorphone, negative control) orally to male and female (in estrus and diestrus...
Source: Biochemical Pharmacology - February 10, 2022 Category: Drugs & Pharmacology Authors: Nicole Arguelles Janielle Richards Ahmed A El-Sherbeni Sharon Miksys Rachel F Tyndale Source Type: research
Sex, estrous cycle, and hormone regulation of CYP2D in the brain alters oxycodone metabolism and analgesia
Biochem Pharmacol. 2022 Feb 7:114949. doi: 10.1016/j.bcp.2022.114949. Online ahead of print.ABSTRACTOpioids, and numerous centrally active drugs, are metabolized by cytochrome P450 2D (CYP2D). There are sex and estrous cycle differences in brain oxycodone analgesia. Here we investigated the mechanism examining the selective role of CYP2D in the brain on sex, estrous cycle, and hormonal regulation. Propranolol, CYP2D-specific mechanism-based inhibitor, or vehicle was delivered into cerebral ventricles 24 hours before administering oxycodone (or oxymorphone, negative control) orally to male and female (in estrus and diestrus...
Source: Biochemical Pharmacology - February 10, 2022 Category: Drugs & Pharmacology Authors: Nicole Arguelles Janielle Richards Ahmed A El-Sherbeni Sharon Miksys Rachel F Tyndale Source Type: research
Antagonism of the mu-delta opioid receptor heterodimer enhances opioid antinociception by activating Src and calcium/calmodulin-dependent protein kinase II signaling
The opioid receptors are important regulators of pain, reward, and addiction. Limited evidence suggests the mu and delta opioid receptors form a heterodimer (MDOR), which may act as a negative feedback brake on opioid-induced analgesia. However, evidence for the MDOR in vivo is indirect and limited, and there are few selective tools available. We recently published the first MDOR-selective antagonist, D24M, allowing us to test the role of the MDOR in mice. We thus cotreated CD-1 mice with D24M and opioids in tail flick, paw incision, and chemotherapy-induced peripheral neuropathy pain models. D24M treatment enhanced oxymor...
Source: Pain - December 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research
Sex and Estrous Cycle Differences in Analgesia and Brain Oxycodone Levels
AbstractSex differences in opioid analgesia occur in rodents and humans, and could be due to differences in drug and metabolite levels. Thus, we investigated the sex and cycle differences in analgesia (nociception) from oxycodone in rats and related these to sex and cycle differences in brain and plasma oxycodone and metabolite levels. Since numerous opioids are CYP2D enzyme substrates and variation in CYP2D alters opioid drug levels and response, we also initiated studies to see if the sex and cycle differences observed might be due to differences in brain CYP2D activity. Across oxycodone doses, females in diestrus had hi...
Source: Molecular Neurobiology - September 28, 2021 Category: Neurology Source Type: research
Molecules, Vol. 26, Pages 5677: Recent Chemical and Pharmacological Developments on 14-Oxygenated-N-methylmorphinan-6-ones
mer
Adequate pain management, particularly chronic pain, remains a major challenge associated with modern-day medicine. Current pharmacotherapy offers unsatisfactory long-term solutions due to serious side effects related to the chronic administration of analgesic drugs. Morphine and structurally related derivatives (e.g., oxycodone, oxymorphone, buprenorphine) are highly effective opioid analgesics, mediating their effects via the activation of opioid receptors, with the mu-opioid receptor subtype as the primary molecular target. However, they also cause addiction and overdose deaths, which has led to a global opioid ...
Source: Molecules - September 18, 2021 Category: Chemistry Authors: Mariana Spetea Helmut Schmidhammer Tags: Review Source Type: research
Relative potency of intravenous oxymorphone compared to other µ opioid agonists in humans — pilot study outcomes
ConclusionsDespite the relatively small sample size, this pilot study detected robust oxymorphone effects. Oxymorphone was far more potent than the comparator opioids, particularly on abuse potential outcomes. Overall, these findings may help explain surveillance reports that demonstrate, after adjusting for prescription availability, oxymorphone is injected at the highest frequency, relative to other prescription opioids. (Source: Psychopharmacology)
Source: Psychopharmacology - August 28, 2021 Category: Psychiatry Source Type: research
A peripheral antinociceptive effects of a bifunctional μ and δ opioid receptor ligand in rat model of inflammatory bladder pain
Neuropharmacology. 2021 Jul 10:108701. doi: 10.1016/j.neuropharm.2021.108701. Online ahead of print.ABSTRACTThere is a need to develop a novel analgesic for pain associated with interstitial cystitis/painful bladder syndrome (IC/PBS). The use of the conventional μ-opioid receptor agonists to manage IC/PBS pain is controversial due to adverse CNS effects. These effects are attenuated in benzylideneoxymorphone (BOM), a low-efficacy μ-opioid receptor agonist/δ-opioid receptor antagonist that attenuates thermal pain and is devoid of reinforcing effects. We hypothesize that BOM will inhibit bladder pain by attenuating respon...
Source: Neuropharmacology - July 13, 2021 Category: Drugs & Pharmacology Authors: Maia Terashvili Bhavana Talluri Watchareepohn Palangmonthip Kenneth A Iczkowski Patrick Sanvanson Bidyut K Medda Banani Banerjee Christopher W Cunningham Jyoti N Sengupta Source Type: research
Cancers, Vol. 13, Pages 2768: Population Pharmacokinetics of Oxycodone and Metabolites in Patients with Cancer-Related Pain
jn L. W. Koolen
Oxycodone is frequently used for treating cancer-related pain, while not much is known about the factors that influence treatment outcomes in these patients. We aim to unravel these factors by developing a population-pharmacokinetic model to assess the pharmacokinetics of oxycodone and its metabolites in cancer patients, and to associate this with pain scores, and adverse events. Hospitalized patients with cancer-related pain, who were treated with oral oxycodone, could participate. Pharmacokinetic samples and patient-reported pain scores and occurrence and severity of nine adverse events were taken eve...
Source: Cancers - June 2, 2021 Category: Cancer & Oncology Authors: Bram C. Agema Astrid W. Oosten Sebastiaan D. T. Sassen Wim J. R. Rietdijk Carin C. D. van der Rijt Birgit C. P. Koch Ron H. J. Mathijssen Stijn L. W. Koolen Tags: Article Source Type: research
Relative potency of intravenous oxymorphone compared to other µ opioid agonists in humans — pilot study outcomes
ConclusionsDespite the relatively small sample size, this pilot study detected robust oxymorphone effects. Oxymorphone was far more potent than the comparator opioids, particularly on abuse potential outcomes. Overall, these findings may help explain surveillance reports that demonstrate, after adjusting for prescription availability, oxymorphone is injected at the highest frequency, relative to other prescription opioids. (Source: Psychopharmacology)
Source: Psychopharmacology - June 1, 2021 Category: Psychiatry Source Type: research
