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Neuropeptides Aug 2023Naloxone has been used as an opioid antagonist to prevent multiple adverse side effects of opioid-like tolerance and hyperalgesia. This study has investigated naloxone...
BACKGROUND
Naloxone has been used as an opioid antagonist to prevent multiple adverse side effects of opioid-like tolerance and hyperalgesia. This study has investigated naloxone combined with morphine to limit pain hypersensitivity. In addition, the expression of brain-derived neurotrophic factor (BDNF) and K Cl cotransporter2 (KCC2) were also studied.
METHODS
Forty-eight adult male Wistar rats (180-220 g) were divided into eight groups, with six rats in each group. Rats were divided into two tolerance and hyperalgesia groups; the sham group, the morphine group, the treatment group (naloxone along with morphine), and the sham group (naloxone along with saline) for eight consecutive days. Tail-flick test was performed on days 1, 5, and 8, and the plantar test on days 1 and 10. On days 8 and 10, the lumbar segments of the spinal cord were collected, and BDNF and KCC2 expression were analyzed using western blotting and immunohistochemistry, respectively.
RESULTS
Results showed that tolerance and hyperalgesia developed following eight days of repeated morphine injection. BDNF expression significantly increased, but KCC2 was downregulated. Co-administration of naloxone and morphine decreased tolerance and hyperalgesia by decreasing BDNF and increasing KCC2 expression, respectively.
CONCLUSION
This study suggests that BDNF and KCC2 may be candidate molecules for decreased morphine tolerance and hyperalgesia.
Topics: Male; Rats; Animals; Morphine; Naloxone; Brain-Derived Neurotrophic Factor; Hyperalgesia; Rats, Wistar; Analgesics, Opioid; Symporters; Spinal Cord
PubMed: 37172403
DOI: 10.1016/j.npep.2023.102345 -
Cancer Dec 2023Clinicians treating cancer-related pain with opioids regularly encounter nonmedical stimulant use (i.e., methamphetamine, cocaine), yet there is little evidence-based...
BACKGROUND
Clinicians treating cancer-related pain with opioids regularly encounter nonmedical stimulant use (i.e., methamphetamine, cocaine), yet there is little evidence-based management guidance. The aim of the study is to identify expert consensus on opioid management strategies for an individual with advanced cancer and cancer-related pain with nonmedical stimulant use according to prognosis.
METHODS
The authors conducted two modified Delphi panels with palliative care and addiction experts. In Panel A, the patient's prognosis was weeks to months and in Panel B the prognosis was months to years. Experts reviewed, rated, and commented on the case using a 9-point Likert scale from 1 (very inappropriate) to 9 (very appropriate) and explained their responses. The authors applied the three-step analytical approach outlined in the RAND/UCLA to determine consensus and level of clinical appropriateness of management strategies. To better conceptualize the quantitative results, they thematically analyzed and coded participant comments.
RESULTS
Consensus was achieved for all management strategies. The 120 Experts were mostly women (47 [62%]), White (94 [78%]), and physicians (115 [96%]). For a patient with cancer-related and nonmedical stimulant use, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering. Buprenorphine/naloxone transition was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis.
CONCLUSION
Study findings provide urgently needed consensus-based guidance for clinicians managing cancer-related pain in the context of stimulant use and highlight a critical need to develop management strategies to address stimulant use disorder in people with cancer.
PLAIN LANGUAGE SUMMARY
Among palliative care and addiction experts, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering in the context of cancer-related pain and nonmedical stimulant use. Buprenorphine/naloxone transition as a harm reduction measure was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis.
Topics: Humans; Female; Male; Analgesics, Opioid; Cancer Pain; Consensus; Buprenorphine; Naloxone; Neoplasms
PubMed: 37691479
DOI: 10.1002/cncr.34921 -
Pain Management Nov 2023Enhancing the effect of peripheral nerve blockade by adding other classes of medications has long history of trial and error. Studies have identified multiple... (Review)
Review
Enhancing the effect of peripheral nerve blockade by adding other classes of medications has long history of trial and error. Studies have identified multiple potentially beneficial adjuncts that work to either speed the onset of analgesia or prolong its duration. The benefits of these adjuncts must be weighed against the risks of systemic negative side effects. To date, the most commonly used adjuncts, and ones with the most robust scientific efficacy are, dexamethasone, dexmedetomidine and buprenorphine. This narrative review will discuss several classes of local anesthetic adjuncts and provide evidence for the clinical efficacy and side effect profile of the most commonly studied medications.
Topics: Humans; Anesthetics, Local; Anesthesia, Conduction; Peripheral Nerves; Buprenorphine
PubMed: 37937437
DOI: 10.2217/pmt-2023-0049 -
Journal of Minimally Invasive Gynecology Oct 2023Discover the rate of post-operative constipation in participants undergoing elective laparoscopy for benign gynecological indications DESIGN: Prospective observational... (Observational Study)
Observational Study
STUDY OBJECTIVE
Discover the rate of post-operative constipation in participants undergoing elective laparoscopy for benign gynecological indications DESIGN: Prospective observational study SETTING: Single site, tertiary level gynecology unit with a focus on pelvic pain and endometriosis.
PATIENTS
Recruited participants were patients of the institution over the age of 18 who had planned to undergo an elective laparoscopy for benign gynecological indications prior to enrolment in the study. Participants were excluded if they were not English speaking, had a chronic bowel condition (with the exception of irritable bowel syndrome), were planned to have bowel surgery, hysterectomy, or converted to laparotomy.
INTERVENTION
In this prospective study, participants completed 3 consecutive surveys. One prior to surgery, one a week post-surgery, and a third 3 months post-surgery. The surveys collected data regarding the participant's bowel habits, pain relief used, laxatives used, and the distress or bother caused by their bowels.
MEASUREMENT AND MAIN RESULTS
Constipation was defined by a modified ROME IV criteria. Opiate use and laxative use were defined by patient-reported tablet counts. The level of distress was measured as a continuously variable scale from 0 to 100. Variables adjusted for included subject's demographics, pre-operative constipation, indication for surgery, duration of surgery, estimated blood loss, opiate use (preoperative, peri-operative, and post-operative), laxative use, and length of stay. A total of 153 participants were recruited, of which 103 completed both the pre-operative and post-operative survey. Post-operative constipation was present in 70% of participants. The mean length of time to first bowel motion was 3 days, with 32% of participants having their first bowel motion after the third post-operative day. The level of bother caused by their bowel habit was higher in the constipation group compared to those without constipation. Post-operatively opiates were used in 84.9% of participants, and laxatives were used in 47.1%. Visits to the general practitioner for constipation occurred in 5.8% of participants.
CONCLUSION
Post-operative constipation is common and bothersome in participants who undergo elective laparoscopy for benign gynecological indications. Analysis of individual variables failed to identify any factors that influenced the rate of constipation.
Topics: Adult; Female; Humans; Middle Aged; Chronic Disease; Constipation; Laparoscopy; Laxatives; Opiate Alkaloids; Prospective Studies; Pelvic Pain; Endometriosis
PubMed: 37321297
DOI: 10.1016/j.jmig.2023.06.005 -
Organic & Biomolecular Chemistry Nov 2023Defluorination of the readily available 21,21,21-trifluorothevinone (7) with Mg + MeSiCl allows the preparation of 21,21-difluorothevinone (10) and 21-fluorothevinone...
Defluorination of the readily available 21,21,21-trifluorothevinone (7) with Mg + MeSiCl allows the preparation of 21,21-difluorothevinone (10) and 21-fluorothevinone (11), which can be used as the starting compounds for syntheses of 21,21-difluoro- and 21-fluoro-substituted relatives of thevinols and orvinols. Taken together, thevinols and orvinols are well known to constitute a family of the highly potent 4,5α-epoxy-18,19--(etheno/ethano)morphinan-type opioid receptor ligands. Alternatively, 10 and 18,19-dihydro-21,21-difluorothevinone (13) have been synthesized by the addition of MeSiCHF to the carbonyl function of thevinal (12) and dihydrothevinal (18) followed by oxidation of the intermediate C(21)-difluorinated secondary alcohols. 21,21-Difluorothevinols were obtained both by the addition of RMgX or RLi to the 21,21-difluoroketones and by the addition of MeSiCHF to the carbonyl function of the non-fluorinated 18,19--(etheno/ethano)morphinan ketones. In general, these addition reactions have been shown to result in mixtures of the C(21)-epimeric alcohols. However, in some cases, the reactions proceeded with high stereoselectivity allowing the isolation of one of the epimeric alcohols by conventional crystallization. Preparations of the 21,21-difluorothevinols bearing an allyl, cyclopropylmethyl, or cyclobutylmethyl group at the N(17) nitrogen are also reported.
Topics: Receptors, Opioid; Morphinans; Oxidation-Reduction; Ligands; Protein Binding; Receptors, Opioid, mu
PubMed: 37947030
DOI: 10.1039/d3ob01577g -
Advanced Emergency Nursing JournalThe emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last... (Review)
Review
The emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last several years, investigations into the use of medications via the nebulization route have greatly increased, with varying degrees of efficacy identified. This route has multiple theoretical advantages. Medications affecting bronchopulmonary function or secretions can be administered directly to the site of action, possibly utilizing a lower dose and hence minimizing side effects. It is also possible to have a faster onset of action compared with other routes, given the enhanced surface area for absorption. One group of medications that has been explored via this route of administration, and is frequently administered in EDs across the nation, is opioids, most notably fentanyl, hydromorphone, and morphine. However multiple questions exist regarding the implementation of these therapies via this route, including efficacy, dosing, and the functional aspects of medication administration that are more complex than that of more traditional routes. The intent of this review is to explore the supporting literature behind the use of nebulized opioids, most specifically fentanyl, hydromorphone, and morphine, in the ED for the treatment of acute pain presentations and provide the most up-to-date guidance for practitioners.
Topics: Humans; Analgesics, Opioid; Emergency Service, Hospital; Fentanyl; Hydromorphone; Morphine
PubMed: 37885077
DOI: 10.1097/TME.0000000000000480 -
Chemical Communications (Cambridge,... Jun 2024The enantioselective synthesis of pharmacologically important 14-hydroxy-6-oxomorphinans is described. 4,5-Desoxynaltrexone and 4,5-desoxynaloxone were prepared using...
The enantioselective synthesis of pharmacologically important 14-hydroxy-6-oxomorphinans is described. 4,5-Desoxynaltrexone and 4,5-desoxynaloxone were prepared using this route and their biological activities against the opioid receptors were measured.
Topics: Stereoisomerism; Morphinans; Naltrexone; Molecular Structure; Narcotic Antagonists; Receptors, Opioid
PubMed: 38787679
DOI: 10.1039/d4cc01788a -
Harm Reduction Journal Aug 2023Drug consumption rooms offer heroin and cocaine consumers a secure and hygienic environment including medical and social guidance. Despite the support and mentoring,...
BACKGROUND
Drug consumption rooms offer heroin and cocaine consumers a secure and hygienic environment including medical and social guidance. Despite the support and mentoring, only sparse information is available about how drug quality, drug prices and user expectations match at these locations. The present study reports analysis of these three parameters in two drug consumption rooms in Luxembourg.
METHODS
Drug users were invited to participate in the project by handing in a few milligrams of the product they planned to consume for chemical analysis and filling out a short questionnaire about the price and their expectations. After consumption, they were asked to report the experienced effects. Drug quality was accessed using LC-Q-ToF and HPLC-UV, and a statistical analysis was carried out of the questionnaires that were correctly filled out.
RESULTS
A total of 513 drug samples have been analyzed. Most consumers were looking for the relaxing/calming effects of heroin and the stimulating effects of cocaine, but they generally overestimated heroin potency and underestimated cocaine potency. No strong correlation based on Spearman's ρ between drug user estimations, drug prices and drug quality was found.
CONCLUSION
To the best of our knowledge, this study is the first to combine drug analysis with heroin and cocaine user feedback about expectation, drug prices and drug effects. The analytical results were of great interest for users and the staff working at the drug consumption rooms. They may be a strong supplementary communication tool for health care workers when discussing effects and risks of highly toxic substance consumption.
Topics: Humans; Cocaine; Heroin; Motivation; Drug Users; Surveys and Questionnaires
PubMed: 37542248
DOI: 10.1186/s12954-023-00837-3 -
South African Medical Journal =... Aug 2023Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the... (Review)
Review
BACKGROUND
Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice.
OBJECTIVE
To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults.
METHODS
A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12 February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines.
RESULTS
We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151 735 participants), resulting in 15 more per 1 000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09 - 6.80; low certainty of evidence; four observational studies, n=167 847 participants), resulting in 45 more per 1 000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews or trials.
CONCLUSION
Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects.
Topics: Adult; Animals; Humans; Hominidae; Morphine Derivatives; Pulmonary Edema; Randomized Controlled Trials as Topic; South Africa; Systematic Reviews as Topic
PubMed: 37882120
DOI: 10.7196/SAMJ.2023.v113i8.348 -
Journal of Substance Use and Addiction... Nov 2023Few studies investigate the natural history of patients on long-term treatment for opioid use disorder (OUD). We evaluated the long-term efficacy, safety, and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Few studies investigate the natural history of patients on long-term treatment for opioid use disorder (OUD). We evaluated the long-term efficacy, safety, and tolerability experience of monthly extended-release buprenorphine (BUP-XR) in participants seeking treatment for OUD, via integrated analysis of phase 3 studies.
METHODS
Study 1 was a 24-week randomized, double-blind, placebo-controlled trial of participants receiving monthly injections of BUP-XR (300 mg × 2, 100 mg × 4 [n = 203] or 300 mg × 6 [n = 201]) or placebo (n = 100). Study 2 was a 48-week, open-label trial enrolling 257 participants who completed study 1 and 412 de novo participants, to receive 6 and 12 BUP-XR injections, respectively. Study 3 was a 24-week, open-label extension enrolling 208 participants who completed study 2 for 6 additional injections. We assessed opioid abstinence as the proportion of urine opioid negative participants by visit and the percentage of each participant's negative opioid assessments during the first 6 months.
RESULTS
In total, 916 participants were treated with BUP-XR or placebo. By the end of 18 months, 92.7 % of the de novo cohort and 81.8 % of the study 1 cohort were urine negative for opioids. Among early nonresponders (percentage of abstinence ≤20 %), 73.1 % were urine negative after 18 months. The longer treatment period was well tolerated, with no new safety concerns, and a low incidence of opioid withdrawal signs and symptoms, and hepatic disorder.
CONCLUSIONS
Extending BUP-XR treatment beyond 6 months sustained improvement in opioid abstinence and was well tolerated, supporting clinical benefit up to 18 months.
TRIAL REGISTRATION
NCT02357901 (study 1); NCT02510014 (study 2); NCT02896296 (study 3).
Topics: Humans; Buprenorphine; Analgesics, Opioid; Narcotic Antagonists; Naltrexone; Opioid-Related Disorders; Injections, Subcutaneous
PubMed: 37657559
DOI: 10.1016/j.josat.2023.209155