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Cureus Aug 2023Public health efforts to reduce the opioid overdose epidemic and treat opioid use disorder (OUD) have met with challenges associated with current non-standardized... (Review)
Review
Public health efforts to reduce the opioid overdose epidemic and treat opioid use disorder (OUD) have met with challenges associated with current non-standardized approaches to managing opioid withdrawal symptoms, such as itching, jitteriness, anxiety, depression, craving, vomiting, diarrhea, insomnia, and anorexia. These symptoms pose substantial obstacles to the safe initiation of medications for OUD, maintenance of long-term sobriety, and prevention of relapse. In clinical practice, multiple medications (polypharmacy) are prescribed to manage these withdrawal symptoms, including ondansetron and promethazine for vomiting and nausea, loperamide and Lomotil for diarrhea, hydroxyzine and doxepin for pruritus, benzodiazepines, the Z-drugs, and melatonin for insomnia, and benzos, tricyclic antidepressants (TCAs), and various serotonergic agents for anxiety. This polypharmacy is associated with an increased risk of adverse drug-drug interactions and adverse drug events, increased medical costs, and increased odds of medication non-adherence and relapse. We propose an alternative single medication, mirtazapine, a noradrenergic and specific serotonergic receptor antagonist, that can be used for myriad symptoms of opioid withdrawal. Case series, clinical studies, and clinical trials have shown mirtazapine to be effective for treating nausea and vomiting resulting from multiple etiologies, including hyperemesis gravidarum and chemotherapy-induced emesis. Other evidence supports the salutary effects of mirtazapine on itching and craving. Research findings support mirtazapine's beneficial effects on diarrhea and anxiety, a consequence of its modulating effects on serotonergic receptors mediating mood and gastrointestinal symptoms. There is also evidence supporting its efficacy as a potent and non-addictive sleep aid, which presents itself as a solution for insomnia associated with opioid withdrawal. The current review presents evidence from extant literature supporting mirtazapine as a one-drug strategy to treat the variety of symptoms of opioid withdrawal. This one-drug strategy has much potential to decrease polypharmacy, adverse drug events, relapse, and healthcare cost and increase the likelihood of prolonged sobriety and better quality of life for people living with OUD.
PubMed: 37736438
DOI: 10.7759/cureus.43821 -
Frontiers in Oncology 2023The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One... (Review)
Review
The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One promising avenue lies in the repurposing of existing drugs. This review explores the impact of phenothiazines, primarily used as antipsychotic agents, on key mechanisms driving tumor growth and metastasis. The cationic and amphiphilic nature of phenothiazines allows interaction with the lipid bilayer of cellular membranes, resulting in alterations in lipid composition, modulation of calcium channels, fluidity, thinning, and integrity of the plasma membrane. This is especially significant in the setting of increased metabolic activity, a higher proliferative rate, and the invasiveness of cancer cells, which often rely on plasma membrane repair. Therefore, properties of phenothiazines such as compromising plasma membrane integrity and repair, disturbing calcium regulation, inducing cytosolic K-RAS accumulation, and sphingomyelin accumulation in the plasma membrane might counteract multidrug resistance by sensitizing cancer cells to membrane damage and chemotherapy. This review outlines a comprehensive overview of the mechanisms driving the anticancer activities of phenothiazines derivates such as trifluoperazine, prochlorperazine, chlorpromazine, promethazine, thioridazine, and fluphenazine. The repurposing potential of phenothiazines paves the way for novel approaches to improve future cancer treatment.
PubMed: 38074670
DOI: 10.3389/fonc.2023.1320621 -
Substance Abuse : Research and Treatment 2023The substance combination of codeine and promethazine, commonly termed /, has been identified as a method that some individuals use to cope with PTSD and other mental...
The substance combination of codeine and promethazine, commonly termed /, has been identified as a method that some individuals use to cope with PTSD and other mental health symptomology. A sample of 1423 adults with self-reported past year lean use was recruited from substance-related Reddit pages to complete a survey about lean, including information about using lean to cope with emotions, thoughts, or feelings. To be included in the sample, persons needed to: (1) be ⩾18 years old, (2) report past year lean use, (3) complete lean use screeners, and (4) pass data quality checks (eg, bot detection). As Reddit is an online forum, no geographic restrictions were placed on study participation. Data on demographic characteristics, lean use, and mental health disorder symptomology were captured from participants. Logistic regression models included anxiety, depression, and trauma as independent variables along with covariates to examine using lean to cope with emotions, thoughts, or feelings in the past 30 days. Most participants were male (n = 1102; 77.4%), with an average age of 26.9 (SD = 5.2) years. Most participants used included codeine as an ingredient in lean (n = 1060; 74.5%); promethazine was added as an ingredient by 31.7% of the sample (n = 451), and the combination of codeine and promethazine was included as ingredients by 13.5% (n = 192) of the sample. Participants with anxiety, lifetime trauma exposure, and who were female had increased odds of using lean to cope with emotions, thoughts, or feelings in the past 30 days. Those with depression and unstable housing exhibited decreased odds of using lean to cope with emotions, thoughts, or feelings in the past 30 days. This study recruited persons via social media to learn more about lean use, especially lean use to cope with mental health symptoms; future population-level studies are needed.
PubMed: 37746632
DOI: 10.1177/11782218231195226 -
Frontiers in Pharmacology 2023Drug-induced QT prolongation and (or) Torsade de Pointes (TdP) is a well-known serious adverse reaction (ADR) for some drugs, but the widely recognized comprehensive...
Drug-induced QT prolongation and (or) Torsade de Pointes (TdP) is a well-known serious adverse reaction (ADR) for some drugs, but the widely recognized comprehensive landscape of culprit-drug of QT prolongation and TdP is currently lacking. To identify the top drugs reported in association with QT prolongation and TdP and provide information for clinical practice. We reviewed the reports related to QT prolongation and TdP in the FDA Adverse Event Reporting System (FAERS) database from January 1, 2004 to December 31, 2022, and summarized a potential causative drug list accordingly. Based on this drug list, the most frequently reported causative drugs and drug classes of QT prolongation and TdP were counted, and the disproportionality analysis for all the drugs was conducted to in detect ADR signal. Furthermore, according to the positive-negative distribution of ADR signal, we integrated the risk characteristic of QT prolongation and TdP in different drugs and drug class. A total of 42,713 reports in FAERS database were considered to be associated with QT prolongation and TdP from 2004 to 2022, in which 1,088 drugs were reported as potential culprit-drugs, and the largest number of drugs belonged to antineoplastics. On the whole, furosemide was the most frequently reported drugs followed by acetylsalicylic acid, quetiapine, citalopram, metoprolol. In terms of drug classes, psycholeptics was the most frequently reported drug classes followed by psychoanaleptics, analgesics, beta blocking agents, drugs for acid related disorders. In disproportionality analysis, 612 drugs showed at least one positive ADR signals, while citalopram, ondansetron, escitalopram, loperamide, and promethazine were the drug with the maximum number of positive ADR signals. However, the positive-negative distribution of ADR signals between different drug classes showed great differences, representing the overall risk difference of different drug classes. Our study provided a real-world overview of QT prolongation and TdP to drugs, and the presentation of the potential culprit-drug list, the proportion of reports, the detection results of ADR signals, and the distribution characteristics of ADR signals may help understand the safety profile of drugs and optimize clinical practice.
PubMed: 38186652
DOI: 10.3389/fphar.2023.1259611 -
European Clinical Respiratory Journal 2023Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without...
BACKGROUND
Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome.
METHODS
Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma.
RESULTS
In our registry of 56,523 patients with COPD, 5,661 collected promethazine ( = 3,723) or melatonin ( = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis.Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27-1.58, < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32-1.77, < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine ( = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94-2.38, <0.0001).
CONCLUSIONS
Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin.
PubMed: 37680536
DOI: 10.1080/20018525.2023.2250604 -
PloS One 2024The concoction known as "lean" containing codeine and promethazine, holds a prominent cultural presence and is often referenced in mass media platforms (e.g., music and...
BACKGROUND
The concoction known as "lean" containing codeine and promethazine, holds a prominent cultural presence and is often referenced in mass media platforms (e.g., music and social media). Surprisingly, there's a scarcity of national data characterizing the use of lean. Therefore, the current study investigated the use of lean using national survey data and online forum participant input, and focused on identifying concurrent substance use, exploring co-administration with other substances (e.g., alcohol, cannabis), and determining lean-related experiences.
METHODS
We analyzed data from the National Survey on Drug Use and Health (NSDUH) spanning 2007-2019, identifying persons who used lean (weighted N = 42,275). Additionally, we conducted a Reddit-based study to gather insights about lean consumtion (N = 192).
RESULTS
The NSDUH data indicated that lean use was most prevalent among teenagers and young adults (ages 13-21), accounting for 66% of the sample. This trend was more pronounced in male respondents (75%) compared to females. Additionally, the use was predominantly observed among Black/African American (29%), Hispanic (28%), and White (33%) populations, with these groups also reporting higher levels of concurrent alcohol and cannabis use. Similarly, findings from Reddit showed that individuals who used lean were predominantly male (67%) and exhibited elevated concurrent rates of alcohol (83%) and cannabis (46%) use in the past 30 days. Moreover, approximately 66% of respondents met criteria for severe lean use disorder, and 37% acknowledged driving under its influence.
CONCLUSION
The NSDUH data found that mostly young adult males reported consuming lean in the past twelve months, though the racial/ethnic breakdown of persons who used lean was diverse. The Reddit data found that most individuals in the sample met the criteria for a substance use disorder pertaining to their lean consumption. These findings underscore the clinical significance and necessity for further controlled research on lean.
Topics: Adolescent; Female; Young Adult; Humans; Male; United States; Codeine; Promethazine; Health Surveys; Hispanic or Latino; Substance-Related Disorders; Cannabis
PubMed: 38527052
DOI: 10.1371/journal.pone.0301024 -
Environmental Science and Pollution... Jul 2023This research aims to remove two phenothiazines, promazine (PRO) and promethazine (PMT), from their individual and binary mixtures using olive tree pruning biochar...
Competitive adsorptive removal of promazine and promethazine from wastewater using olive tree pruning biochar: operational parameters, kinetics, and equilibrium investigations.
This research aims to remove two phenothiazines, promazine (PRO) and promethazine (PMT), from their individual and binary mixtures using olive tree pruning biochar (BC-OTPR). The impact of individual and combinatory effects of operational variables was evaluated for the first time using central composite design (CCD). Simultaneous removal of both drugs was maximized utilizing the composite desirability function. At low concentrations, the uptake of PRO and PMT from their individual solutions was achieved with high efficiency of 98.64%, 47.20 mg/g and 95.87%, 38.16 mg/g, respectively. No major differences in the removal capacity were observed for the binary mixtures. Characterization of BC-OTPR confirmed successful adsorption and showed that the OTPR surface was predominantly mesoporous. Equilibrium investigations revealed that the Langmuir isotherm model best describes the sorption of PRO/PMT from their individual solutions with maximum adsorption capacities of 640.7 and 346.95 mg/g, respectively. The sorption of PRO/PMT conforms to the pseudo-second-order kinetic model. Regeneration of the adsorbent surface was successfully done with desorption efficiencies of 94.06% and 98.54% for PRO and PMT, respectively, for six cycles.
Topics: Wastewater; Promethazine; Olea; Promazine; Kinetics; Adsorption; Charcoal; Water Pollutants, Chemical; Hydrogen-Ion Concentration
PubMed: 37326738
DOI: 10.1007/s11356-023-27688-6 -
International Journal of Surgery Case... Oct 2023Baclofen is a γ -aminobutyric acid (GABA) agonist used to treat spasticity; however, it may be toxic at dosages above 200 mg. The psychological, nervous,...
INTRODUCTION
Baclofen is a γ -aminobutyric acid (GABA) agonist used to treat spasticity; however, it may be toxic at dosages above 200 mg. The psychological, nervous, cardiovascular, gastrointestinal, musculoskeletal, and respiratory systems are all affected. This report represents a case with the rare respiratory complications brought on by baclofen toxicity: atelectasis and pneumomediastinum.
PRESENTATION OF CASE
A 19-year-old female was admitted to the emergency department after attempting suicide by taking 20 baclofen tablets (500 mg). Imaging revealed pneumomediastinum, atelectasis, and a leftward displacement of mediastinal structures. Her therapy included a chest tube to relieve the pneumomediastinum and sodium valproate, promethazine, biperiden, and quetiapine for neurological symptoms. Four days after being admitted, she was successfully extubated without any complications.
DISCUSSION
Baclofen activates GABA-A and GABA-B receptors. High doses of baclofen may induce central nervous system and respiratory depression, requiring intensive care. GABA receptors may cause hallucinations, delusions, and agitation in baclofen overdose. High dosages of baclofen may cause bronchial and bronchiolar muscular spasms, leading to breathing problems and atelectasis. Recent animal studies on baclofen toxicity showed that increased alveolar pressure, circulatory abnormalities, edema, alveolar hemorrhages, and infiltration cause rupture and pneumomediastinum. Pneumomediastinum may need bed rest, oxygen, antitussives, and analgesics, but severe cases may necessitate a chest tube.
CONCLUSION
A high index of suspicion is required for early diagnosis of acute baclofen poisoning, which could manifest as respiratory complications, including pneumomediastinum and atelectasis. Since most cases are benign, it is still crucial for clinicians to detect complications early for further management.
PubMed: 37801962
DOI: 10.1016/j.ijscr.2023.108901