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Journal of Medical Toxicology :... Apr 2024
Topics: Humans; Naltrexone; Narcotic Antagonists; Alcoholism
PubMed: 38393519
DOI: 10.1007/s13181-024-00998-y -
Drug and Therapeutics Bulletin Aug 2023Etminan M, Rezaeianzadeh R, Kezouh A, et al. Association between sublingual buprenorphine-naloxone exposure and dental disease. JAMA. 2022;328:2269-71. (Review)
Review
Etminan M, Rezaeianzadeh R, Kezouh A, et al. Association between sublingual buprenorphine-naloxone exposure and dental disease. JAMA. 2022;328:2269-71.
Topics: Humans; Administration, Sublingual; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug-Related Side Effects and Adverse Reactions; Naloxone; Narcotic Antagonists; Opioid-Related Disorders
PubMed: 37353308
DOI: 10.1136/dtb.2023.000034 -
Blocking Palmitoylation of Apelin Receptor Alleviates Morphine Tolerance in Neuropathic Cancer Pain.International Journal of Biological... 2024Neuropathic cancer pain (NCP) is an important symptom in patients with cancer. However, significant analgesic tolerance and other side effects critically hamper the...
Neuropathic cancer pain (NCP) is an important symptom in patients with cancer. However, significant analgesic tolerance and other side effects critically hamper the administration of morphine. Protein palmitoylation mediated by the DHHC family may be involved in the glial activation and inflammatory responses underlying organ failure. In this study, we investigated the key role of protein palmitoylation in cancer pain and sought to target palmitoylation to suppress morphine tolerance. We found that long-term use of morphine led to the accumulation of the morphine metabolite, morphine-3-glucuronide, and activated ERK1/2 and microglia to release inflammatory factors through the apelin receptor APLNR. Palmitoyltransferase ZDHHC9 was upregulated in NCP, and APLNR was palmitylated to protect it from lysosomal degradation and to maintain its stability. We also designed competitive inhibitors of APLNR palmitoylation to inhibit the development of NCP, release of inflammatory factors, and attenuation of morphine tolerance. Therefore, targeting APLNR palmitoylation in combination with morphine is a potent method for cancer pain treatment. Our data provide a basis for the future clinical use of related drugs combined with morphine for the treatment of cancer-related pain.
Topics: Humans; Morphine; Apelin Receptors; Cancer Pain; Lipoylation; Neuralgia; Neoplasms
PubMed: 38164190
DOI: 10.7150/ijbs.86888 -
Missouri Medicine 2024
Topics: Naloxone; Humans; Narcotic Antagonists; Drug Overdose
PubMed: 38694597
DOI: No ID Found -
Journal of Addiction MedicineBuprenorphine is not reliably stocked in many pharmacies, and pharmacy-level barriers may deter patients from opioid use disorder care. We surveyed all outpatient...
OBJECTIVES
Buprenorphine is not reliably stocked in many pharmacies, and pharmacy-level barriers may deter patients from opioid use disorder care. We surveyed all outpatient pharmacies in Philadelphia to describe variation in buprenorphine access and developed a map application to aid in identifying pharmacies that stock the medication.
METHODS
Using a dataset from the Bureau of Professional and Occupational Affairs, we conducted a telephone survey of operating outpatient pharmacies (N = 422) about their buprenorphine stocking and dispensing practices. We used ArcGIS Pro 3.0.3 to join US Census Bureau ZIP code-level race and ethnicity data, conduct descriptive analyses, and create a map application.
RESULTS
We collected data from 351 pharmacies (83% response rate). Two hundred thirty-eight pharmacies (68%) indicated that they regularly stock buprenorphine; 6 (2%) would order it when a prescription is sent. Ninety-one (26%) said that they do not stock or order buprenorphine, and 16 (5%) were unsure. We identified 137 "easier access" pharmacies (39%), meaning they regularly stock buprenorphine, dispense to new patients, and have no dosage maximums. Zip codes with predominantly White residents had a median (interquartile range) of 3 (2-4) "easier access" pharmacies, and those with predominantly Black residents a median (interquartile range) of 2 (1-4.5). Nine zip codes had no "easier access" pharmacies, and 3 had only one; these 3 zip codes are areas with predominantly Black residents.
CONCLUSIONS
Buprenorphine access is not equitable across Philadelphia and a quarter of pharmacies choose not to carry the medication. Our map application may be used to identify pharmacies in Philadelphia that stock buprenorphine.
Topics: Buprenorphine; Humans; Philadelphia; Opioid-Related Disorders; Health Services Accessibility; Pharmacies; Opiate Substitution Treatment; Narcotic Antagonists
PubMed: 38345212
DOI: 10.1097/ADM.0000000000001284 -
Cleveland Clinic Journal of Medicine Sep 2023Buprenorphine is a safe and effective treatment for opioid use disorder but remains underutilized because a major challenge of conventional buprenorphine initiation... (Review)
Review
Buprenorphine is a safe and effective treatment for opioid use disorder but remains underutilized because a major challenge of conventional buprenorphine initiation (termed ) is that the patient must already be in opioid withdrawal. Previous legal barriers and clinician lack of familiarity with the unique pharmacology of buprenorphine have also limited its use. In this review, we outline changes regarding buprenorphine prescribing laws and physician perceptions of buprenorphine. We also review buprenorphine pharmacology and novel low-dose buprenorphine induction procedures that can be adopted in primary care settings to improve treatment acceptability, retention, and outcomes.
Topics: Humans; Buprenorphine; Opioid-Related Disorders; Physicians; Substance Withdrawal Syndrome; Primary Health Care
PubMed: 37657832
DOI: 10.3949/ccjm.90a.23022 -
BMJ Supportive & Palliative Care Jan 2024Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using... (Review)
Review
INTRODUCTION
Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using opioids other than morphine.
METHODS
The author conducted a non-systematic literature review in the PubMed/Medline and Embase until 4 October 2022. Eligible studies have evaluated the efficacy of opioids other than morphine for cancer-related breathlessness. Studies focused on sedation, anaesthesia, paediatric patients, opioid toxicity or basic research were excluded. Reviews/meta-analyses and non-English language publications were also excluded.
RESULTS
A total of 1556 records were identified, of which 23 studies including 469 patients who were treated with fentanyl (n=223), oxycodone (n=171) and hydromorphone (n=75) were considered eligible. Six phase II randomised clinical trials (RCTs), four observational studies and four case reports of fentanyl were found. For breathlessness on exertion, fentanyl yielded promising results, but no RCT showed significant superiority of fentanyl to placebo or morphine. For terminal breathlessness, three RCTs, five non-randomised or observational studies and one case report on oxycodone or hydromorphone were found. Although the results of the observational studies suggested that oxycodone and hydromorphone might be effective alternatives to morphine, the superiority over placebo or non-inferiority to morphine had not been demonstrated in the RCTs.
CONCLUSION
As an alternative to morphine, the author recommends fentanyl for breathless crisis or breathlessness on exertion, and oxycodone or hydromorphone for terminal breathlessness in advanced cancer. Larger and well-designed studies based on firm research policies are needed to confirm this current knowledge.
Topics: Child; Humans; Analgesics, Opioid; Dyspnea; Fentanyl; Hydromorphone; Morphine; Neoplasms; Oxycodone
PubMed: 37468224
DOI: 10.1136/spcare-2022-004115 -
JAMA Network Open Aug 2023The DRAMES (Décès en Relation avec l'Abus de Médicaments Et de Substances) register is a database of drug-related deaths with the aim of identifying the psychoactive...
IMPORTANCE
The DRAMES (Décès en Relation avec l'Abus de Médicaments Et de Substances) register is a database of drug-related deaths with the aim of identifying the psychoactive substances associated with and estimating the trends in these deaths. Our novel approach is based on the collection of data on all deaths for which toxicology experts have performed analyses.
OBJECTIVE
To describe drug-related deaths in France and report trends over an 11-year period.
DESIGN, SETTING, AND PARTICIPANTS
This case series used a national register to assess 4460 drug-related deaths that occurred from 2011 to 2021 in France. Data analyses were performed from January 1, 2012, to December 31, 2022.
MAIN OUTCOMES AND MEASURES
Demographic characteristics; medical and substance abuse history; forensic autopsy findings; and toxicology reports.
RESULTS
Among the 4460 deceased individuals (mean [SD] age, 37.8 [10.5] years), the mortality rate was highest among men (sex ratio, 4.4:1). Of the deaths involving a single or predominant drug, the legal substitution product, methadone, was the leading cause of death during the entire study period, ahead of heroin-44.7% and 35.9% for methadone vs 15.8% and 21.8% for heroin in 2011 and 2021, respectively. Between 2011 and 2021, most of the drug-related deaths shifted from licit to illicit drugs, and statistically significant variations were found for buprenorphine, cocaine, heroin, methadone, and other licit opioids. Deaths related to polydrug use increased from 23.2% in 2011 to 30.6% in 2021. In this context, opioids remained associated with most deaths, with at least 1 opioid being involved in approximately 9 of 10 cases (85.9%) in 2021. However, the main trend was the dramatic increase in drug combinations with cocaine, from less than one-third of cases in 2011 (30.8%) to more than half in 2021 (57.8%).
CONCLUSIONS AND RELEVANCE
This case series assessment of 4460 drug-related deaths found that opioids used alone or in combination were the main contributor to drug-related deaths, despite having a lower prevalence than other drugs. This finding is similar to that of other countries; however, in France licit methadone was the leading cause of opioid-related deaths (ahead of heroin) during the study period. Deaths associated with use of cannabis, new psychoactive substances, and stimulants (including amphetamine-type stimulants and cocaine, especially in combination) have increased and should be closely monitored.
Topics: Male; Humans; Adult; Drug Users; Analgesics, Opioid; Heroin; Methadone; Cocaine
PubMed: 37647066
DOI: 10.1001/jamanetworkopen.2023.31398 -
JAMA Internal Medicine Dec 2023Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments.
IMPORTANCE
Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments.
OBJECTIVE
To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization.
DESIGN, SETTING, AND PARTICIPANTS
The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after.
INTERVENTION
The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine.
MAIN OUTCOMES AND MEASURES
The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up.
RESULTS
During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70).
CONCLUSIONS AND RELEVANCE
The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03407638.
Topics: Humans; Female; Middle Aged; Adolescent; Young Adult; Adult; Aged; Aged, 80 and over; Male; Naltrexone; Opiate Substitution Treatment; Leadership; Opioid-Related Disorders; Buprenorphine
PubMed: 37902748
DOI: 10.1001/jamainternmed.2023.5701 -
Frontiers in Public Health 2024Opioid-induced respiratory depression (OIRD) deaths are ~80,000 a year in the US and are a major public health issue. Approximately 90% of fatal opioid-related deaths... (Review)
Review
Opioid-induced respiratory depression (OIRD) deaths are ~80,000 a year in the US and are a major public health issue. Approximately 90% of fatal opioid-related deaths are due to synthetic opioids such as fentanyl, most of which is illicitly manufactured and distributed either on its own or as an adulterant to other drugs of abuse such as cocaine or methamphetamine. Other potent opioids such as nitazenes are also increasingly present in the illicit drug supply, and xylazine, a veterinary tranquilizer, is a prevalent additive to opioids and other drugs of abuse. Naloxone is the main treatment used to reverse OIRD and is available as nasal sprays, prefilled naloxone injection devices, and generic naloxone for injection. An overdose needs to be treated as soon as possible to avoid death, and synthetic opioids such as fentanyl are up to 50 times more potent than heroin, so the availability of new, higher-dose, 5-mg prefilled injection or 8-mg intranasal spray naloxone preparations are important additions for emergency treatment of OIRDs, especially by lay people in the community. Higher naloxone doses are expected to reverse a synthetic overdose more rapidly and the current formulations are ideal for use by untrained lay people in the community. There are potential concerns about severe withdrawal symptoms, or pulmonary edema from treatment with high-dose naloxone. However, from the perspective of first responders, the balance of risks would point to administration of naloxone at the dose required to combat the overdose where the risk of death is very high. The presence of xylazines as an adulterant complicates the treatment of OIRDs, as naloxone is probably ineffective, although it will reverse the respiratory depression due to the opioid. For these patients, hospitalization is particularly vital. Education about the benefits of naloxone remains important not only in informing people about how to treat emergency OIRDs but also how to obtain naloxone. A call to emergency services is also essential after administering naloxone because, although the patient may revive, they may overdose again later because of the short half-life of naloxone and the long-lasting potency of fentanyl and its analogs.
Topics: Humans; Naloxone; Analgesics, Opioid; Narcotic Antagonists; Fentanyl; Heroin; Drug Overdose
PubMed: 38481848
DOI: 10.3389/fpubh.2024.1346109