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Plant Physiology Nov 2019Although opiate biosynthesis has been largely elucidated, and cell-to-cell transport has been long postulated, benzylisoquinoline alkaloid (BIA) transporters from opium...
Although opiate biosynthesis has been largely elucidated, and cell-to-cell transport has been long postulated, benzylisoquinoline alkaloid (BIA) transporters from opium poppy () have not been reported. Investigation of a purine permease-type sequence within a recently discovered opiate biosynthetic gene cluster led to the discovery of a family of nine homologs designated as BIA uptake permeases (BUPs). Initial expression studies in engineered yeast hosting segments of the opiate pathway showed that six of the nine BUP homologs facilitated dramatic increases in alkaloid yields. Closer examination revealed the ability to uptake a variety of BIAs and certain pathway precursors (e.g. dopamine), with each BUP displaying a unique substrate acceptance profile. Improvements in uptake for yeast expressing specific BUPs versus those devoid of the heterologous transporters were high for early intermediates (300- and 25-fold for dopamine and norcoclaurine, respectively), central pathway metabolites [10-fold for ()-reticuline], and end products (30-fold for codeine). A coculture of three yeast strains, each harboring a different consecutive segment of the opiate pathway and , was able to convert exogenous Levodopa to 3 ± 4 mg/L codeine via a 14-step bioconversion process involving over a dozen enzymes. is highly expressed in opium poppy latex and is localized to the plasma membrane. The discovery of the BUP transporter family expands the role of purine permease-type transporters in specialized metabolism, and provides key insight into the cellular mechanisms involved in opiate alkaloid biosynthesis in opium poppy.
Topics: Benzylisoquinolines; Cell Membrane; Codeine; Gene Expression Regulation, Plant; Nucleobase Transport Proteins; Papaver; Plant Proteins
PubMed: 31467164
DOI: 10.1104/pp.19.00565 -
The European Journal of Neuroscience Jul 2020Emotional arousal is one of several factors that determine the strength of a memory and how efficiently it may be retrieved. The systems at play are multifaceted; on one... (Review)
Review
The role of catecholamines in modulating responses to stress: Sex-specific patterns, implications, and therapeutic potential for post-traumatic stress disorder and opiate withdrawal.
Emotional arousal is one of several factors that determine the strength of a memory and how efficiently it may be retrieved. The systems at play are multifaceted; on one hand, the dopaminergic mesocorticolimbic system evaluates the rewarding or reinforcing potential of a stimulus, while on the other, the noradrenergic stress response system evaluates the risk of threat, commanding attention, and engaging emotional and physical behavioral responses. Sex-specific patterns in the anatomy and function of the arousal system suggest that sexually divergent therapeutic approaches may be advantageous for neurological disorders involving arousal, learning, and memory. From the lens of the triple network model of psychopathology, we argue that post-traumatic stress disorder and opiate substance use disorder arise from maladaptive learning responses that are perpetuated by hyperarousal of the salience network. We present evidence that catecholamine-modulated learning and stress-responsive circuitry exerts substantial influence over the salience network and its dysfunction in stress-related psychiatric disorders, and between the sexes. We discuss the therapeutic potential of targeting the endogenous cannabinoid system; a ubiquitous neuromodulator that influences learning, memory, and responsivity to stress by influencing catecholamine, excitatory, and inhibitory synaptic transmission. Relevant preclinical data in male and female rodents are integrated with clinical data in men and women in an effort to understand how ideal treatment modalities between the sexes may be different.
Topics: Catecholamines; Female; Humans; Male; Memory; Norepinephrine; Opiate Alkaloids; Stress Disorders, Post-Traumatic
PubMed: 32125035
DOI: 10.1111/ejn.14714 -
Journal of Substance Abuse Treatment Feb 2022In 2018, the Baltimore City Health Department launched a mobile clinic called Healthcare on The Spot, which offers low-threshold buprenorphine services integrated with...
INTRODUCTION
In 2018, the Baltimore City Health Department launched a mobile clinic called Healthcare on The Spot, which offers low-threshold buprenorphine services integrated with health care services to meet the needs of people who use drugs. In addition to buprenorphine management, The Spot offers testing and treatment for hepatitis C, sexually transmitted infections, and HIV, as well as pre-exposure prophylaxis for HIV, wound care, vaccinations, naloxone distribution, and case management.
METHODS AND MATERIALS
This cohort analysis includes clinical service data from the first 15 months of The Spot mobile clinic, from September 4, 2018, to November 23, 2019. The Spot co-located with the Baltimore syringe services program in five locations across the city. Descriptive data are provided for patient demographics and services provided, as well as percent of patients retained in buprenorphine treatment at one and three months. Logistic regression identified factors associated with retention at three months.
RESULTS
The Spot mobile clinic provided services to 569 individuals from September 4, 2018, to November 23, 2019, including prescribing buprenorphine to 73.8% and testing to more than 70% for at least one infectious disease. Patients receiving a prescription for buprenorphine were more likely to be tested for HIV, hepatitis C, and sexually transmitted infections, as well as receive treatment for hepatitis C and preventive services including vaccination and naloxone distribution. The Spot initiated HIV treatment for four patients and HIV pre-exposure prophylaxis for twelve patients. More than 32% of patients had hepatitis C; nineteen of these patients initiated treatment for hepatitis C with eight having a documented cure. Buprenorphine treatment retention was 56.0% at one month and 26.2% at three months. Patients who were Black or receiving treatment for hepatitis C were more likely to be retained in buprenorphine treatment at three months.
CONCLUSIONS
Increasing access to integrated medical services and drug treatment through low-threshold, community-based models of care can be an effective tool for addressing the effects of drug use.
Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Hepatitis C; Humans; Mobile Health Units; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 34238629
DOI: 10.1016/j.jsat.2021.108553 -
Journal of General Internal Medicine Aug 2020
Topics: Humans; Naloxone; Pharmaceutical Services; Pharmacies; Pharmacy; Prescriptions
PubMed: 32193816
DOI: 10.1007/s11606-020-05760-y -
Canadian Journal of Surgery. Journal... 2023Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres...
BACKGROUND
Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres moving away from using epidural analgesia, there is the need to evaluate alternative opiate sparing techniques for postoperative analgesia. We sought to determine if rectus sheath catheters (RSCs) had an opiate sparing and analgesic effect compared with standard care alone (opiate analgesia).
METHODS
We conducted a retrospective pre- and postintervention cohort study of patients undergoing pancreaticoduodenectomy at a single tertiary academic hospital in Toronto, Canada, between April 2018 and December 2019. All patients undergoing a pancreaticoduodenectomy were eligible for inclusion. Among the 101 patients identified, 84 (61 control, 23 RSCs) were analyzed after exclusion criteria were applied (epidural analgesia, admission to intensive care intubated or reintubated within the first 96 hours). The pre-intervention group received a semi-standardized course of analgesics, including intravenous hydromorphone, acetaminophen, ketamine, with or without nonsteroidal anti-inflammatory, and with or without intravenous lidocaine; the latter 2 drugs were at the individual anesthesiologist and surgeon's preference. For the postintervention group, the same course of analgesics were used, with the addition of RSCs. These were inserted at the end of the operation, with a loading dose of ropivacaine administered and followed by a programmed intermittent bolus regime for 72-96 hours. The primary outcome measure was total postoperative opiate consumption (oral morphine equivalents). Secondary outcomes included pain scores (numeric rating scale) and treatment-related adverse effects.
RESULTS
Opiate consumption (oral morphine equivalents) at 96 hours was significantly lower (median 188 mg, interquartile range [IQR] 112-228 v. 242.4 mg, IQR 166.8-352) with and without RSC, respectively ( = 0.01). The RSC group used significantly less opiates at each time point from 24 hours postoperatively, with no significant difference in pain scores between the groups and no significant catheter-related complications.
CONCLUSION
The use of RSCs was associated with significant reductions in postoperative opiate consumption. Given the ease of placement and management, with minimal complications, RSCs should be incorporated into a course of postoperative multimodal analgesia. A large scale randomized controlled trial should be conducted to further investigate these findings.
Topics: Humans; Opiate Alkaloids; Analgesics, Opioid; Retrospective Studies; Pain, Postoperative; Cohort Studies; Pancreaticoduodenectomy; Treatment Outcome; Analgesics; Morphine; Postoperative Complications; Catheters
PubMed: 37442583
DOI: 10.1503/cjs.006922 -
American Journal of Nephrology 2020Population-based studies show there is a high prevalence of chronic kidney disease (CKD) patients suffering from chronic pain. While opiates are frequently prescribed in... (Comparative Study)
Comparative Study
BACKGROUND
Population-based studies show there is a high prevalence of chronic kidney disease (CKD) patients suffering from chronic pain. While opiates are frequently prescribed in non-dialysis-dependent CKD (NDD-CKD) patients, there may be toxic accumulation of metabolites, particularly among those progressing to end-stage renal disease (ESRD). We examined the association of opiate versus other analgesic use during the pre-ESRD period with post-ESRD mortality among NDD-CKD patients transitioning to dialysis.
METHODS
We examined a national cohort of US Veterans with NDD-CKD who transitioned to dialysis over 2007-14. Among patients who received ≥1 prescription(s) in the Veterans Affairs (VA) Healthcare System within 1 year of transitioning to dialysis, we examined associations of pre-ESRD analgesic status, defined as opiate, gabapentin/pregabalin, other non-opiate analgesic, versus no analgesic use, with post-ESRD mortality using multivariable Cox models.
RESULTS
Among 57,764 patients who met eligibility criteria, pre-ESRD opiate and gabapentin/pregabalin use were each associated with higher post-ESRD mortality (ref: no analgesic use), whereas non-opiate analgesic use was not associated with higher mortality in expanded case-mix analyses: HRs (95% CIs) 1.07 (1.05-1.10), 1.07 (1.01-1.13), and 1.00 (0.94-1.06), respectively. In secondary analyses, increasing frequency of opiate prescriptions exceeding 1 opiate prescription in the 1-year pre-ESRD period was associated with incrementally higher post-ESRD mortality (ref: no analgesic use).
CONCLUSIONS
In NDD-CKD patients transitioning to dialysis, pre-ESRD opiate and gabapentin/pregabalin use were associated with higher post-ESRD mortality, whereas non-opiate analgesic use was not associated with death. There was a graded association between increasing frequency of pre-ESRD opiate use and incrementally higher mortality.
Topics: Aged; Aged, 80 and over; Analgesics, Non-Narcotic; Chronic Pain; Databases, Factual; Disease Progression; Drug Prescriptions; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Opiate Alkaloids; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Transitional Care; United States; United States Department of Veterans Affairs
PubMed: 32777779
DOI: 10.1159/000509451 -
Journal of Analytical Toxicology Feb 2022The purpose of this research was to develop and validate an analytical method for the detection and quantification of noroxymorphone-3β-D-glucuronide (NOMG),...
The purpose of this research was to develop and validate an analytical method for the detection and quantification of noroxymorphone-3β-D-glucuronide (NOMG), oxymorphone-3β-D-glucuronide (NOMG), noroxymorphone (NOM), oxymorphone (OM), 6α-oxycodol (αOCL), 6β-oxycodol (βOCL), noroxycodone (NOC) and oxycodone (OC) in urine by liquid chromatography tandem mass spectrometry to be used in a human study. The method was validated according to the Academy Standards Board Standard Practices for Method Development in Forensic Toxicology. The method was then applied to a single-dose pilot study of a subject. Urine samples were collected from the subject after ingesting 10-mg OC as an immediate-release tablet. Additionally, urine specimens (n = 15) that had previously been confirmed positive for OC were analyzed using the validated method. The calibration range for NOMG and OMG was 0.05-10 μg/mL; for all other analytes, it was 0.015-10 μg/mL. Validation parameters such as bias, precision, carryover and dilution integrity, all met the validation criteria. After the method was validated, urine samples from the first subject in the controlled dose study were analyzed. It was observed that OC, NOC and OMG contained the highest concentrations and were present in either the 0.5 or 1 h void. NOC and OMG were detected until the 48 h collection, while OC was detectable till the 24 h collection. Time to reach maximum concentration (Tmax) in the urine was achieved within 1.5 h for OC and within 3 h for NOC and OMG. Maximum concentration (Cmax) in the urine for OC, NOC and OMG was 3.15, 2.0 and 1.56 μg/mg, respectively. OC concentrations in authentic urines ranged from 0.015 to 12 μg/mL. Ranges for NOMG and OMG were 0.054-9.7 μg/mL and 0.14-67 μg/mL, respectively. A comprehensive method for the quantification of NOMG, OMG, NOM, OM, αOCL, βOCL, NOC and OC in urine was optimized and met the validation criteria. The concentrations of NOMG and OMG presented in this study provide the details needed in the forensic community to better comprehend OC pharmacokinetics.
Topics: Chromatography, Liquid; Humans; Oxycodone; Oxymorphone; Pilot Projects; Tandem Mass Spectrometry
PubMed: 33270113
DOI: 10.1093/jat/bkaa186 -
Molecules (Basel, Switzerland) Feb 2021Codeine is derived from morphine, an opioid analgesic, and has weaker analgesic and sedative effects than the parent molecule. This weak opioid is commonly used in... (Review)
Review
Codeine is derived from morphine, an opioid analgesic, and has weaker analgesic and sedative effects than the parent molecule. This weak opioid is commonly used in combination with other drugs for over-the-counter cough relief medication. Due to the psychoactive properties of opioid drugs, the easily obtained codeine often becomes subject to misuse. Codeine misuse has emerged as a concerning public health issue due to its associated adverse effects such as headache, nausea, vomiting, and hemorrhage. Thus, it is very important to develop reliable analytical techniques to detect codeine for both quality control of pharmaceutical formulations and identifying drug misuse in the community. This review aims to provide critical outlooks on analytical methods applicable to the determination of codeine.
Topics: Chemistry Techniques, Analytical; Codeine; Humans
PubMed: 33557168
DOI: 10.3390/molecules26040800 -
Identifying and Characterizing Medical Advice-Seekers on a Social Media Forum for Buprenorphine Use.International Journal of Environmental... May 2022Background: Online communities such as Reddit can provide social support for those recovering from opioid use disorder. However, it is unclear whether and how...
Background: Online communities such as Reddit can provide social support for those recovering from opioid use disorder. However, it is unclear whether and how advice-seekers differ from other users. Our research addresses this gap by identifying key characteristics of r/suboxone users that predict advice-seeking behavior. Objective: The objective of this analysis is to identify and describe advice-seekers on Reddit for buprenorphine-naloxone use using text annotation, social network analysis, and statistical modeling techniques. Methods: We collected 5258 posts and their comments from Reddit between 2014 and 2019. Among 202 posts which met our inclusion criteria, we annotated each post to determine which were advice-seeking (n = 137) or not advice-seeking (n = 65). We also annotated each posting user’s buprenorphine-naloxone use status (current versus formerly taking and, if currently taking, whether inducting or tapering versus other stages) and quantified their connectedness using social network analysis. To analyze the relationship between Reddit users’ advice-seeking and their social connectivity and medication use status, we constructed four models which varied in their inclusion of explanatory variables for social connectedness and buprenorphine use status. Results: The stepwise model containing “total degree” (p = 0.002), “using: inducting/tapering” (p < 0.001), and “using: other” (p = 0.01) outperformed all other models. Reddit users with fewer connections and who are currently using buprenorphine-naloxone are more likely to seek advice than those who are well-connected and no longer using the medication, respectively. Importantly, advice-seeking behavior is most accurately predicted using a combination of network characteristics and medication use status, rather than either factor alone. Conclusions: Our findings provide insights for the clinical care of people recovering from opioid use disorder and the nature of online medical advice-seeking overall. Clinicians should be especially attentive (e.g., through frequent follow-up) to patients who are inducting or tapering buprenorphine-naloxone or signal limited social support.
Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Humans; Opioid-Related Disorders; Social Media; Social Networking
PubMed: 35627818
DOI: 10.3390/ijerph19106281 -
WMJ : Official Publication of the State... Feb 2024Opioids prescribed for postoperative pain have exceeded patient need in the United States, playing a significant role in the opioid epidemic. In the preintervention...
BACKGROUND
Opioids prescribed for postoperative pain have exceeded patient need in the United States, playing a significant role in the opioid epidemic. In the preintervention phase of this project (September 2018 - March 2019), a chart review and patient survey revealed that patients were prescribed double the number of opioids they consumed following gynecologic surgery.
OBJECTIVE
To ascertain whether an educational intervention recommending opiate prescriptions based on postoperative opioid use decreases gynecologic surgeons' opiate prescriptions.
METHODS
An educational intervention implemented in January 2021 communicated the discrepancy between patient need and medications prescribed and made prescribing recommendations for common gynecologic procedures. A postintervention (February 2021 - April 2021) retrospective chart review ascertained postoperative opioid prescribing practices. Residents were surveyed about their prescribing practices in June 2021. Descriptive statistics compared each phase.
RESULTS
For laparoscopic hysterectomy, the median morphine milligram equivalent (MME) was 150 (IQR 112.5-166.9) for preintervention and 150 (IQR 112.5-150) postintervention. For vaginal hysterectomy, median MME declined from 150 (IQR 112.5-225) to 112.5 (IQR 112.5-150). For laparoscopic surgery without hysterectomy, the median MME was 75 for both preintervention (IQR 75-120) and postintervention (IQR 60-80). For vaginal surgery without hysterectomy median MME went from 75 (IQR 75-142.5) to 54 (IQR 22.5-112.5). Median MME for hysteroscopy and dilation and curettage was 0 for both phases. When surveyed, residents reported prescribing lower amounts than actual prescribing practices.
CONCLUSIONS
Despite education informing gynecologic surgeons that their opioid prescribing exceeded patient need, prescribing practices did not change. The difference between actual and resident-reported prescribing practices warrants further investigation.
Topics: Humans; Female; Analgesics, Opioid; Retrospective Studies; Practice Patterns, Physicians'; Gynecologic Surgical Procedures; Opiate Alkaloids; Endrin
PubMed: 38436635
DOI: No ID Found