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Molecules (Basel, Switzerland) Aug 2020Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their... (Review)
Review
Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their pharmacology, interactions, safety profiles, and how pharmacology is being manipulated to misuse these common medications, with the aim to expand on the subject outlined by the authors focusing on abuse prevention and prevalence rates. The reviewed literature was identified in several online databases through searches conducted with phrases created by combining the international non-proprietary names of the drugs with terms related to drug misuse. The results show that OTC opioids are misused as an alternative for illicit narcotics, or prescription-only opioids. The potency of codeine and loperamide is strongly dependent on the individual enzymatic activity of CYP2D6 and CYP3A4, as well as P-glycoprotein function. Codeine can also be utilized as a substrate for clandestine syntheses of more potent drugs of abuse, namely desomorphine ("Krokodil"), and morphine. The dangerous methods used to prepare these substances can result in poisoning from toxic chemicals and impurities originating from the synthesis procedure. OTC opioids are generally safe when consumed in accordance with medical guidelines. However, the intake of supratherapeutic amounts of these substances may reveal surprising traits of common medications.
Topics: Analgesics, Opioid; Codeine; Drug Misuse; Humans; Loperamide; Nonprescription Drugs
PubMed: 32867117
DOI: 10.3390/molecules25173905 -
JAMA Psychiatry Jul 2021Opioid use disorder (OUD) is a significant cause of morbidity and mortality in the US, yet many individuals with OUD do not receive treatment.
IMPORTANCE
Opioid use disorder (OUD) is a significant cause of morbidity and mortality in the US, yet many individuals with OUD do not receive treatment.
OBJECTIVE
To assess the cost-effectiveness of OUD treatments and association of these treatments with outcomes in the US.
DESIGN AND SETTING
This model-based cost-effectiveness analysis included a US population with OUD.
INTERVENTIONS
Medication-assisted treatment (MAT) with buprenorphine, methadone, or injectable extended-release naltrexone; psychotherapy (beyond standard counseling); overdose education and naloxone distribution (OEND); and contingency management (CM).
MAIN OUTCOMES AND MEASURES
Fatal and nonfatal overdoses and deaths throughout 5 years, discounted lifetime quality-adjusted life-years (QALYs), and costs.
RESULTS
In the base case, in the absence of treatment, 42 717 overdoses (4132 fatal, 38 585 nonfatal) and 12 660 deaths were estimated to occur in a cohort of 100 000 patients over 5 years, and 11.58 discounted lifetime QALYs were estimated to be experienced per person. An estimated reduction in overdoses was associated with MAT with methadone (10.7%), MAT with buprenorphine or naltrexone (22.0%), and when combined with CM and psychotherapy (range, 21.0%-31.4%). Estimated deceased deaths were associated with MAT with methadone (6%), MAT with buprenorphine or naltrexone (13.9%), and when combined with CM, OEND, and psychotherapy (16.9%). MAT yielded discounted gains of 1.02 to 1.07 QALYs per person. Including only health care sector costs, methadone cost $16 000/QALY gained compared with no treatment, followed by methadone with OEND ($22 000/QALY gained), then by buprenorphine with OEND and CM ($42 000/QALY gained), and then by buprenorphine with OEND, CM, and psychotherapy ($250 000/QALY gained). MAT with naltrexone was dominated by other treatment alternatives. When criminal justice costs were included, all forms of MAT (with buprenorphine, methadone, and naltrexone) were associated with cost savings compared with no treatment, yielding savings of $25 000 to $105 000 in lifetime costs per person. The largest cost savings were associated with methadone plus CM. Results were qualitatively unchanged over a wide range of sensitivity analyses. An analysis using demographic and cost data for Veterans Health Administration patients yielded similar findings.
CONCLUSIONS AND RELEVANCE
In this cost-effectiveness analysis, expanded access to MAT, combined with OEND and CM, was associated with cost-saving reductions in morbidity and mortality from OUD. Lack of widespread MAT availability limits access to a cost-saving medical intervention that reduces morbidity and mortality from OUD. Opioid overdoses in the US likely reached a record high in 2020 because of COVID-19 increasing substance use, exacerbating stress and social isolation, and interfering with opioid treatment. It is essential to understand the cost-effectiveness of alternative forms of MAT to treat OUD.
Topics: Adult; Buprenorphine; Combined Modality Therapy; Cost-Benefit Analysis; Delayed-Action Preparations; Female; Humans; Male; Methadone; Middle Aged; Naloxone; Opiate Overdose; Opiate Substitution Treatment; Opioid-Related Disorders; Psychotherapy; Treatment Outcome
PubMed: 33787832
DOI: 10.1001/jamapsychiatry.2021.0247 -
Nature Communications Oct 2022The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms...
The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAc) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAc) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAc neurons impairs reward seeking behavior, while silencing of NAc or NAc→LH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion.
Topics: Mice; Animals; Nucleus Accumbens; Reward; Ventral Tegmental Area; Dopaminergic Neurons; Opiate Alkaloids
PubMed: 36271048
DOI: 10.1038/s41467-022-33843-3 -
British Journal of Anaesthesia Oct 2019
Topics: Humans; Naloxone
PubMed: 31420087
DOI: 10.1016/j.bja.2019.07.007 -
Anesthesiology Jun 2020Intrathecal opioids are routinely administered during spinal anesthesia for postcesarean analgesia. The effectiveness of intrathecal morphine for postcesarean analgesia... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Intrathecal opioids are routinely administered during spinal anesthesia for postcesarean analgesia. The effectiveness of intrathecal morphine for postcesarean analgesia is well established, and the use of intrathecal hydromorphone is growing. No prospective studies have compared the effectiveness of equipotent doses of intrathecal morphine versus intrathecal hydromorphone as part of a multimodal analgesic regimen for postcesarean analgesia. The authors hypothesized that intrathecal morphine would result in superior analgesia compared with intrathecal hydromorphone 24 h after delivery.
METHODS
In this single-center, double-blinded, randomized trial, 138 parturients undergoing scheduled cesarean delivery were randomized to receive 150 µg of intrathecal morphine or 75 µg of intrathecal hydromorphone as part of a primary spinal anesthetic and multimodal analgesic regimen; 134 parturients were included in the analysis. The primary outcome was the numerical rating scale score for pain with movement 24 h after delivery. Static and dynamic pain scores, nausea, pruritus, degree of sedation, and patient satisfaction were assessed every 6 h for 36 h postpartum. Total opioid consumption was recorded.
RESULTS
There was no significant difference in pain scores with movement at 24 h (intrathecal hydromorphone median [25th, 75th] 4 [3, 5] and intrathecal morphine 3 [2, 4.5]) or at any time point (estimated difference, 0.5; 95% CI, 0 to 1; P = 0.139). Opioid received in the first 24 h did not differ between groups (median [25th, 75th] oral morphine milligram equivalents for intrathecal hydromorphone 30 [7.5, 45.06] vs. intrathecal morphine 22.5 [14.0, 37.5], P = 0.769). From Kaplan-Meier analysis, the median time to first opioid request was 5.4 h for hydromorphone and 12.1 h for morphine (log-rank test P = 0.200).
CONCLUSIONS
Although the hypothesis was that intrathecal morphine would provide superior analgesia to intrathecal hydromorphone, the results did not confirm this. At the doses studied, both intrathecal morphine and intrathecal hydromorphone provide effective postcesarean analgesia when combined with a multimodal analgesia regimen.
Topics: Adult; Analgesia, Epidural; Analgesia, Obstetrical; Analgesics, Opioid; Cesarean Section; Double-Blind Method; Female; Humans; Hydromorphone; Male; Morphine; Pain, Postoperative; Treatment Outcome
PubMed: 32251031
DOI: 10.1097/ALN.0000000000003283 -
Molecules (Basel, Switzerland) May 2022-dealkylation, the removal of an -alkyl group from an amine, is an important chemical transformation which provides routes for the synthesis of a wide range of... (Review)
Review
-dealkylation, the removal of an -alkyl group from an amine, is an important chemical transformation which provides routes for the synthesis of a wide range of pharmaceuticals, agrochemicals, bulk and fine chemicals. -dealkylation of amines is also an important in vivo metabolic pathway in the metabolism of xenobiotics. Identification and synthesis of drug metabolites such as -dealkylated metabolites are necessary throughout all phases of drug development studies. In this review, different approaches for the -dealkylation of amines including chemical, catalytic, electrochemical, photochemical and enzymatic methods will be discussed.
Topics: Amines; Dealkylation
PubMed: 35630770
DOI: 10.3390/molecules27103293 -
Journal of Substance Abuse Treatment Nov 2022At age 16, I injected morphine for the first time, and then started injecting heroin. By most standards, I was highly functioning, although I eventually became addicted....
At age 16, I injected morphine for the first time, and then started injecting heroin. By most standards, I was highly functioning, although I eventually became addicted. I was and remain socioeconomically privileged, but my relationship to heroin resulted in behaviors and consequences that I never could have conceived of, and which I sometimes strain to remember occurred. My life now is stable and conventional. Some aspects of my past addiction are unerasable, but the most salient of those are the social and legal consequences of having a criminal record-not any hallmarks of a chronic brain disease or disorder. I do not consider myself "in recovery." Rather, I am recovered, by standards both my own and derived from clinical nosology. I have been in sustained remission for over a decade. Yet feelings are not facts, as is often said. I still use alcohol, and occasionally (though not recently) I have used other drugs, so there remains the possibility that my brain is indeed "diseased" and I am not objectively recovered, my self-assessment notwithstanding. My aim in writing about my lived experience of drug use, addiction, and recovery is to highlight the heterogeneity of people's experiences and the insight that personal narratives can provide. Debates about the brain disease model of addiction are often confined to academia, with the real-world, unintended consequences of the "disease" label seldom considered. Stigmatization of people with addiction comes from moralizing about drug use but may also originate from well-intended labels. I posit that we should not need labels to care about addicted people and make scientifically informed treatment accessible. Addicted people deserve help because they either need or want it, regardless of labels that presume to describe the etiology or likely trajectory of their problems. I conclude that some labels, even those needed for clinical classification of human behavior, may be pernicious. Clinicians and researchers have an obligation to reflect more deeply on the implications of the disease conceptualization of complex human behaviors such as addiction.
Topics: Adolescent; Behavior, Addictive; Brain Diseases; Heroin; Humans; Substance-Related Disorders
PubMed: 36108442
DOI: 10.1016/j.jsat.2022.108874 -
Canadian Family Physician Medecin de... Dec 2020
Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Humans; Naloxone; Opioid-Related Disorders; Substance Withdrawal Syndrome
PubMed: 33334955
DOI: 10.46747/cfp.6612891 -
American Journal of Respiratory and... Aug 2020
Topics: Critical Care; Humans; Intensive Care Units; Opiate Alkaloids; Patient Discharge; Respiration, Artificial
PubMed: 32464072
DOI: 10.1164/rccm.202005-1815ED -
British Journal of Hospital Medicine... Sep 2022The forearm is the most common site of fracture in children. At the time of initial assessment, a thorough examination and neurovascular assessment of the limb is... (Review)
Review
The forearm is the most common site of fracture in children. At the time of initial assessment, a thorough examination and neurovascular assessment of the limb is necessary. X-rays allow evaluation of the fracture location and type, in addition to the degree of displacement. With the help of intranasal opiates, manipulation of fracture fragments can be performed in the emergency department. Immobilisation in plaster is the gold standard treatment for paediatric forearm fractures where the degree of displacement is within acceptable parameters. Manipulation and casting should be followed by orthogonal radiographs and a repeated neurovascular assessment of the limb. Oral analgesia and safety netting information should be provided on discharge and the child should be reviewed in fracture clinic within a week of the injury. This article reviews the British Orthopaedic Association Standards for Trauma and Orthopaedics for the early management of paediatric forearm fractures that do not require operative management.
Topics: Child; Forearm; Forearm Injuries; Humans; Opiate Alkaloids; Radiography; Radius Fractures
PubMed: 36193916
DOI: 10.12968/hmed.2021.0564