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1.
Yakugaku Zasshi ; 142(7): 755-760, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35781505

RESUMO

Naldemedine (Nal) is widely used as a therapeutic drug against opioid-induced constipation. However, patients in phase III trials are limited to those with good performance status (PS). Cancer patients may have inferior PS owing to progression of symptoms and adverse events from chemotherapy. Therefore, it is important to survey the efficacy of Nal in patients with poor PS. This study aimed to evaluate Nal efficacy in patients with poor PS. We retrospectively investigated patients from July 2017 to June 2019 and compared Nal efficacy between patients with good and poor PS. The efficacy of Nal was evaluated using changes in the number of spontaneous bowel movements 7 days before and after the introduction of Nal with reference to previous reports. Multivariate analysis was performed to reveal whether poor PS affects Nal efficacy. In total, 141 patients at the Hokkaido University Hospital were analyzed. The effective rate of Nal from day 1 to day 7 of administration was 71.7% and 71.4% in the patients with good and poor PS, respectively, that from day 1 to day 2 of administration was 61.1% and 57.1%, respectively, and that from day 3 to day 7 of administration was 60.2% and 71.4%, respectively, suggesting an absence of significant differences. Furthermore, results of multivariate analysis showed that "best supportive care" and "body weight (55 kg and above)" reduced Nal efficacy. In conclusion, Nal showed similar effectiveness in patients with poor PS as that in those with good PS.


Assuntos
Analgésicos Opioides , Antagonistas de Entorpecentes , Analgésicos Opioides/efeitos adversos , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Humanos , Naltrexona/análogos & derivados , Estudos Retrospectivos
2.
Neurosci Lett ; 786: 136816, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35901909

RESUMO

Mechanical allodynia has been studied in chronic naltrexone-treated people (N.T.P.) and rats (N.T.R.). After persistent naltrexone administration, patients acquired static and dynamic mechanical allodynia, as measured by von Frey filament (vFf) and brush stimulations. Pregabalin and levodopa administrations in N.T.P. significantly reduced allodynic behaviour, albeit these molecules did not completely stop it. As evidenced by the deployment of the vFf, subchronic treatment with Naltrexone delivered peripherally or intrathecally induced allodynic behaviour in rats. Increased expressions of two pain markers, pERK1/2 and PKCγ, in the spinal dorsal horn laminae were associated with naltrexone-induced allodynic behaviour. After vFf stimulation, pERK1/2 expression was substantially higher (p < 0.001) in superficial spinal dorsal horn laminae than in non-stimulated or naive non-stimulated rats. In addition, when compared to control rats, N.T.R. showed a substantial (p < 0.001) increase in PKCγ expression. PKCγ expression was found to be strong in lamina IIi and laminae III-IV. A cellular mechanism is proposed for the naltrexone effect. In both people and rats, Naltrexone induces static mechanical allodynia, according to this study.


Assuntos
Hiperalgesia , Naltrexona , Animais , Humanos , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Naltrexona/farmacologia , Dor , Ratos , Ratos Sprague-Dawley , Corno Dorsal da Medula Espinal/metabolismo
3.
Addict Sci Clin Pract ; 17(1): 36, 2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35850782

RESUMO

BACKGROUND: The opioid antagonist extended-release naltrexone (XR-NTX) in the treatment of opioid use disorder (OUD) is effective in terms of safety, abstinence from opioid use and retention in treatment. However, it is unclear how patients experience and adjust to losing the possibility of achieving an opioid effect. This qualitative study is the first to explore how people with opioid dependence experience XR-NTX treatment, focusing on the process of treatment over time. METHODS: Using a purposive sampling strategy, semi-structured interviews were undertaken with 19 persons with opioid use disorder (15 men, four women, 22-55 years of age) participating in a clinical trial of XR-NTX in Norway. The interviewees had received at least three XR-NTX injections. Qualitative content analysis with an inductive approach was used. FINDINGS: Participants described that XR-NTX treatment had many advantages. However they still faced multiple challenges, some of which they were not prepared for. Having to find a new foothold and adapt to no longer gaining an effect from opioids due to the antagonist medication was challenging. This was especially true for those struggling emotionally and transitioning into the harmful use of non-opioid substances. Additional support was considered crucial. Even so, the treatment led to an opportunity to participate in society and reclaim identity. Participants had strong goals for the future and described that XR-NTX enabled a more meaningful life. Expectations of a better life could however turn into broken hopes. Although participants were largely optimistic about the future, thinking about the end of treatment could cause apprehension. CONCLUSIONS: XR-NTX treatment offers freedom from opioids and can facilitate the recovery process for people with OUD. However, our findings also highlight several challenges associated with XR-NTX treatment, emphasizing the importance of monitoring emotional difficulties and increase of non-opioid substances during treatment. As opioid abstinence in itself does not necessarily equal recovery, our findings underscore the importance of seeing XR-NTX as part of a comprehensive, individualized treatment approach. TRIAL REGISTRATION: Clinicaltrials.gov # NCT03647774, first Registered: Aug 28, 2018.


Assuntos
Naltrexona , Transtornos Relacionados ao Uso de Opioides , Adulto , Analgésicos Opioides/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Adulto Jovem
4.
Acta Neurobiol Exp (Wars) ; 82(2): 157-169, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35833815

RESUMO

This study was designed to investigate the involvement of opioidergic/nitrergic systems in the anticonvulsant effect of mefloquine, compared with chloroquine, in mice. Seizures were induced by pentylenetetrazol and maximal electroshock. Mice were randomly subjected to receive mefloquine or chloroquine thirty minutes in advance. The role of opioidergic/nitrergic systems was shown by co­administration of pharmacological intervention and nitrite levels measurement in mice hippocampi. Results indicated that mefloquine (40 mg/kg) and chloroquine (5 mg/kg) significantly decreased the occurrence of tonic hindlimb extension. Also, mefloquine 120 mg/kg and chloroquine 5 mg/kg significantly increased seizure latency and decreased mortality rate. Mefloquine decreased seizure frequency too. Besides, mefloquine (20 mg/kg) and chloroquine (5, 10 mg/kg) significantly increased seizure threshold. Interestingly, L­NAME, 7­NI and naltrexone pre­treatment reversed the anticonvulsant effects of both mefloquine (20 mg/kg) and chloroquine (5 mg/kg). Moreover, co­administration of minimal­effective doses of morphine with mefloquine/chloroquine (both 1 mg/kg) potentiated anticonvulsant effects, which was reversed by naltrexone and endorsed the involvement of opioid receptors. Also, nitrite levels in mice hippocampi remarkably increased after treatment with both mefloquine (20 mg/kg) and chloroquine (5 mg/kg). To conclude, mefloquine could protect the central nervous system against seizures in PTZ/MES­induced models through opioidergic/nitrergic pathways, with similarity to chloroquine effects.


Assuntos
Anticonvulsivantes , Pentilenotetrazol , Convulsões , Animais , Anticonvulsivantes/farmacologia , Cloroquina/farmacologia , Modelos Animais de Doenças , Eletrochoque , Mefloquina/farmacologia , Camundongos , Naltrexona , Nitritos , Pentilenotetrazol/toxicidade , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
5.
J Acquir Immune Defic Syndr ; 90(S1): S206-S214, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35703773

RESUMO

BACKGROUND: Given substance use disorders (SUDs) among people with HIV are highly prevalent, integrating SUD services within HIV service settings is needed to help end the HIV epidemic. In this study, we assessed the setting-intervention fit (SIF) of 9 evidence-based SUD interventions: acamprosate, disulfiram, oral naltrexone, injectable naltrexone, oral buprenorphine, injectable buprenorphine, contingency management, motivational interviewing, and cognitive behavioral therapy (CBT). SETTING: Clinical and nonclinical HIV service organizations (HSOs) in the United States. METHODS: In May 2020, a stakeholder-engaged real-time Delphi was completed with 202 HSOs. HSO respondents rated the extent to which each SUD intervention was fundable, implementable, retainable, sustainable, scalable, and timely for their HSO, and these 6 items were summed into an SIF score (possible range of 0-18). RESULTS: Motivational interviewing had the highest average SIF score (11.42), with SIF scores above the midpoint (9.5) for clinical (11.51) and nonclinical HSOs (11.36). For nonclinical HSOs, none of the other interventions were above the midpoint. For clinical HSOs, the average SIF scores were above the midpoint for CBT (10.97) and oral buprenorphine (9.51). Multivariate regression analyses, which controlled for characteristics of the HSO respondent, revealed geographic region of the United States and whether the HSO currently offered any substance use services as 2 of the best predictors of SIF scores. CONCLUSIONS: Notwithstanding the need to improve the SIF for the other evidence-based SUD interventions, motivational interviewing, CBT, and oral buprenorphine are currently the evidence-based SUD interventions with greatest perceived fit for integration within HSOs in the United States.


Assuntos
Buprenorfina , Infecções por HIV , Transtornos Relacionados ao Uso de Substâncias , Técnica Delfos , Medicina Baseada em Evidências , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Naltrexona , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/terapia , Estados Unidos/epidemiologia
6.
Contrast Media Mol Imaging ; 2022: 6572499, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685666

RESUMO

This study aimed to explore the effect of naltrexone on the expression of lipid metabolism-related proteins in liver steatosis induced by endoplasmic reticulum stress in mice. Thirty inbred mice (C57BL/6J) were divided into three groups: group A (normal control group), group B (model control), and group C (naltrexone group). The male mice in group A were fed a regular diet, and the mice in groups B and C were fed a high-fat diet. Liver steatosis was observed by histopathological sections. Mouse liver (alanine aminotransferase (ALT) and triglyceride (TC)) content (glucose regulatory protein (GRP78), endoplasmic reticulum transmembrane protein kinase-1α (IRE-1α), C/EBP source protein (CHOP), cysteine-containing aspartate proteolytic enzyme 12 (caspase-12), B lymphoma-2 (Bcl-2), and cell death mediator (Bim)) was detected. Compared with group A, bodyweight, fat weight, ALT, TG, and hepatic steatosis were significantly increased in B and C groups (P < 0.05); compared with group B, group C showed a significant decrease in bodyweight, fat weight, ALT, TG, and hepatic steatosis (P < 0.05). Compared with group A, the expression levels of GRP78, IRE-1α, CHOP, caspase-12, and Bim in liver tissue of groups B and C mice were increased. Bcl-2 decreased (P < 0.05). Compared with group B and group C after naltrexone intervention, the expression levels of GRP78, IRE-1α, CHOP, caspase-12, and Bim decreased significantly, and Bcl-2 increased significantly (P < 0.05). Naltrexone can effectively reduce bodyweight and adipose tissue accumulation, reduce liver fat lesions, improve the expression of lipid metabolism-related proteins and endoplasmic reticulum stress, reduce liver lipid synthesis, and protect liver cells.


Assuntos
Fígado Gorduroso , Metabolismo dos Lipídeos , Animais , Caspase 12 , Estresse do Retículo Endoplasmático , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naltrexona/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2
7.
Alcohol Clin Exp Res ; 46(6): 1094-1102, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35723682

RESUMO

RATIONALE: Investigations show that medications for alcohol use disorders (MAUD) reduce heavy drinking and relapses. However, only 1.6% of individuals with alcohol use disorders (AUD) receive MAUD across care settings. The epidemiology of MAUD prescribing in the acute care setting is incompletely described. We hypothesized that MAUD would be under prescribed in inpatient acute care hospital settings compared to the outpatient, emergency department (ED), and inpatient substance use treatment settings. METHODS: We evaluated electronic health record (EHR) data from adult patients with an International Classification of Diseases, 10th revision (ICD-10) alcohol-related diagnosis in the University of Colorado Health (UCHealth) system between January 1, 2016 and 31 December, 2019. Data from patients with an ICD-10 diagnosis code for opioid use disorder and those receiving MAUD prior to their first alcohol-related episode were excluded. The primary outcome was prescribing of MAUD, defined by prescription of naltrexone, acamprosate, and/or disulfiram. We performed bivariate and multivariate analyses to identify independent predictors of MAUD prescribing at UCHealth. RESULTS: We identified 48,421 unique patients with 136,205 alcohol-related encounters at UCHealth. Encounters occurred in the ED (42%), inpatient acute care (17%), inpatient substance use treatment (18%), or outpatient primary care (12%) settings. Only 2270 (5%) patients received MAUD across all settings. Female sex and addiction medicine consults positively predicted MAUD prescribing. In contrast, encounters outside inpatient substance use treatment, Hispanic ethnicity, and black or non-white race were negative predictors of MAUD prescribing. Compared to inpatient substance use treatment, inpatient acute care hospitalizations for AUD was associated with a 93% reduced odds of receiving MAUD. CONCLUSIONS: AUD-related ED and inpatient acute care hospital encounters in our healthcare system were common. Nevertheless, prescriptions for MAUD were infrequent in this population, particularly in inpatient settings. Our findings suggest that the initiation of MAUD for patients with alcohol-related diagnoses in acute care settings deserves additional evaluation.


Assuntos
Alcoolismo , Transtornos Relacionados ao Uso de Opioides , Adulto , Alcoolismo/tratamento farmacológico , Alcoolismo/epidemiologia , Colorado/epidemiologia , Atenção à Saúde , Etanol/uso terapêutico , Feminino , Humanos , Naltrexona/uso terapêutico
8.
J Clin Psychiatry ; 83(4)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35759785

RESUMO

Background: Stimulant use has substantially increased among people with opioid use disorder (OUD) and is associated with worse treatment outcomes. This study's objective was to compare risk of stimulant-related emergency department (ED) and hospital admissions associated with exposure to bupropion, OUD medication (buprenorphine, naltrexone, and methadone), and selective serotonin reuptake inhibitors (SSRIs; active comparator) relative to days without active prescriptions for medication.Methods: This recurrent-event, case-crossover study used insurance claims from 51,084 individuals with OUD enrolled in the IBM MarketScan (2006-2016) Databases who had at least 1 stimulant-related ED or hospital admission. Conditional logistic regression models estimated the risk of admissions between days without active prescriptions and days with prescriptions for bupropion, OUD medication, and SSRIs. Secondary analyses were conducted by stimulant subtype (cocaine; amphetamine) and event subtype (falls, injuries, or poisonings; psychotic events).Results: Compared to days without active prescriptions, days with bupropion treatment were associated with decreased odds of stimulant-related ED or hospital admissions (odds ratio [OR] = 0.77; 95% confidence interval [CI], 0.72-0.82) Among OUD medications, we observed strong protective associations with decreased admissions for buprenorphine (OR = 0.67; 95% CI, 0.64-0.71), naltrexone (OR = 0.65; 95% CI, 0.60-0.70), and methadone (OR = 0.59; 95% CI, 0.51-0.67). The SSRI active comparator group was associated with a small protective association with decreased admissions (OR = 0.90; 95% CI, 0.86-0.93). These effects were sustained in secondary analyses stratifying by stimulant and event subtype.Conclusions: Bupropion and OUD medication, including both naltrexone and opioid agonists, are associated with fewer stimulant-related ED or hospital admissions in patients with OUD. Bupropion may show promise as adjunctive therapy targeting stimulant-specific poisoning risk.


Assuntos
Buprenorfina , Estimulantes do Sistema Nervoso Central , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Buprenorfina/efeitos adversos , Bupropiona/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estudos Cross-Over , Humanos , Metadona/efeitos adversos , Naltrexona/efeitos adversos , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia
9.
CNS Drugs ; 36(6): 605-616, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35644903

RESUMO

Olanzapine is a second-generation antipsychotic with established efficacy in several psychiatric disease states, but its use is limited because of weight gain and metabolic side effects. Samidorphan is a novel opioid antagonist that binds to mu-opioid, kappa-opioid, and delta-opioid receptors and is hypothesized to reduce cravings for high-calorie foods thus attenuating antipsychotic-induced weight gain. The combination product olanzapine/samidorphan was approved by the US Food and Drug Administration in June 2021 for the treatment of schizophrenia and bipolar I disorder; this article reviews the pharmacological properties of oral olanzapine/samidorphan and its clinical efficacy and tolerability with a focus on mitigation of olanzapine-induced weight gain in these patient populations. In clinical trials, the combination of olanzapine/samidorphan was associated with significantly less weight gain and smaller increases in waist circumference as compared with olanzapine monotherapy. Olanzapine/samidorphan demonstrated similar efficacy as olanzapine monotherapy and was well tolerated. Weight gain and metabolic side effects associated with olanzapine monotherapy can result in tolerability issues and potentially medication nonadherence. Olanzapine/samidorphan is an effective treatment for schizophrenia and bipolar I disorder with less weight gain than olanzapine monotherapy.


Assuntos
Antipsicóticos , Transtorno Bipolar , Esquizofrenia , Analgésicos Opioides/uso terapêutico , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Humanos , Naltrexona/análogos & derivados , Olanzapina/efeitos adversos , Esquizofrenia/tratamento farmacológico , Aumento de Peso
11.
J Pharmacol Exp Ther ; 382(2): 181-187, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35643857

RESUMO

Methocinnamox (MCAM), a long-acting µ-opioid receptor antagonist, attenuates the positive reinforcing effects of opioids, such as heroin and fentanyl, suggesting it could be an effective treatment of opioid use disorder (OUD). Because treatment of OUD often involves repeated administration of a medication, this study evaluated effects of daily injections of a relatively small dose of MCAM on fentanyl self-administration and characterized the shift in the fentanyl dose-effect curve. Rhesus monkeys (3 males and 2 females) lever-pressed for intravenous infusions of fentanyl (0.032-10 µg/kg infusion) or cocaine (32-100 µg/kg infusion) under a fixed-ratio 30 schedule. MCAM (0.032 mg/kg) or naltrexone (0.0032-0.032 mg/kg) was administered subcutaneously 60 or 15 minutes, respectively, before sessions. When administered acutely, naltrexone and MCAM decreased fentanyl self-administration, with effects of naltrexone lasting less than 24 hours and effects of MCAM lasting for up to 3 days. Daily MCAM treatment attenuated responding for fentanyl, but not cocaine; effects were maintained for the duration of treatment with responding recovering quickly (within 2 days) following discontinuation of treatment. MCAM treatment shifted the fentanyl dose-effect curve in a parallel manner approximately 20-fold to the right. Naltrexone pretreatment decreased fentanyl intake with equal potency before and after MCAM treatment, confirming sensitivity of responding to antagonism by an opioid receptor antagonist. Although antagonist effects of treatment with a relatively small dose were surmountable, MCAM produced sustained and selective attenuation of opioid self-administration, supporting the view that it could be an effective treatment of OUD. SIGNIFICANCE STATEMENT: Opioid use disorder and opioid overdose continue to be significant public health challenges despite the availability of effective treatments. Methocinnamox (MCAM) is a long-acting µ-opioid receptor antagonist that blocks the reinforcing and ventilatory depressant effects of opioids in nonhuman subjects. This study demonstrates that daily treatment with MCAM reliably and selectively decreases fentanyl self-administration, further supporting the potential therapeutic utility of this novel antagonist.


Assuntos
Cinamatos , Derivados da Morfina , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides , Animais , Cinamatos/uso terapêutico , Cocaína/farmacologia , Relação Dose-Resposta a Droga , Feminino , Fentanila/farmacologia , Macaca mulatta , Masculino , Derivados da Morfina/uso terapêutico , Naltrexona/farmacologia , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/farmacologia , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Receptores Opioides mu , Autoadministração
12.
J Control Release ; 348: 841-848, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35752252

RESUMO

The complexity of scale-up manufacturing of PLGA microparticles creates a significant challenge when transitioning from benchtop-scale formulation development into larger clinical scale batches. Minor changes in the initial formulation composition (e.g., PLGA molecular weight, solvent type, and drug concentration) and processing parameters (e.g., extraction kinetics and drying condition) during scale-up production can result in significantly different performance of the prepared microparticles. The objectives of the present study were to highlight the in vitro and in vivo performance of a candidate benchtop-scale batch created with a rotor-stator mixer, transitioned into an in-line manufacturing process at ~15× scale of a long-acting naltrexone formulation. Physicochemical properties (such as drug loading, residual benzyl alcohol content, and morphology) as well as the in vitro release characteristics of the prepared naltrexone microparticles between the benchtop-scale and in-line process pilot-scale were determined. The pharmacokinetics of the naltrexone microspheres were investigated using the rat model. The results demonstrate that while the morphologies of the particles were different from a visual assessment and slight differences were observed in the in vitro release profiles, the in vivo pharmacokinetics illustrate similar kinetics. Our study shows that scale-up production having the same drug release kinetics can be made by controlling the formulation and processing parameters.


Assuntos
Ácido Láctico , Ácido Poliglicólico , Animais , Portadores de Fármacos/química , Ácido Láctico/química , Microesferas , Naltrexona , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos
13.
JAMA Netw Open ; 5(6): e2214765, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35648400

RESUMO

Importance: COVID-19 disrupted delivery of buprenorphine and naltrexone treatment for opioid use disorder (OUD), and during the pandemic, members of racial and ethnic minority groups experienced increased COVID-19 and opioid overdose risks compared with White individuals. However, whether filled buprenorphine and naltrexone prescriptions varied across racial and ethnic groups during the COVID-19 pandemic remains unknown. Objective: To investigate whether disruptions in filled buprenorphine and naltrexone prescriptions differed by race and ethnicity and insurance status or payer type. Design, Setting, and Participants: This cross-sectional study used retail pharmacy claims from May 2019 to June 2021 from the Symphony Health database, which includes 92% of US retail pharmacy claims, with race and ethnicity data spanning all insurance status and payer categories. Interrupted time series were used to estimate levels and trends of dispensed buprenorphine and naltrexone prescriptions before and after pandemic onset. Included individuals were those who filled buprenorphine and extended-release naltrexone prescriptions. Data were analyzed from July 2021 through March 2022. Main Outcomes and Measures: Weekly rates of dispensed buprenorphine and extended-release naltrexone prescription fills per 1000 patients and proportion of longer (ie, ≥14 days' supply) buprenorphine prescription fills were calculated. Analyses were stratified by patient race and ethnicity and further by insurance status and payer type for White and Black patients. Results: A total of 1 556 860 individuals who filled buprenorphine prescriptions (4359 Asian [0.3%], 94 657 Black [6.1%], 55 369 Hispanic [3.6%], and 664 779 White [42.7%]) and 127 506 individuals who filled extended-release naltrexone prescriptions (344 Asian [0.3%], 8186 Black [6.4%], 5343 Hispanic [4.2%], and 53 068 White [41.6%]) from May 6, 2019, to June 5, 2021, were analyzed. Prepandemic increases in buprenorphine fill rate flattened for all groups after COVID-19 onset (30.5 percentage point difference in trend; P < .001) compared with prepandemic trends. Significant level decreases in buprenorphine fills (ranging from 2.5% for Black patients; P = .009 to 4.0% for Hispanic patients; P = .009) at pandemic onset were observed for members of racial and ethnic minority groups but not White patients. At pandemic onset, rate of buprenorphine fills decreased in level for Medicare and cash-paying patients but with greater decreases for Black patients (Medicare: 10.0%; P < .001; cash: 20.0%; P < .001) than White patients (Medicare: 3.5%; P = .004; cash: 15.0%; P < .001). No decreases were found among Medicaid patients. Unlike buprenorphine, extended-release naltrexone had uniform level (from 10.0% for White patients with private insurance; P < .001 to 23.3% for Black patients with Medicare; P < .001) and trend (from 15.5 percentage points for White patients with Medicaid; P = .001 to 52.0 percentage points for Black patients with private insurance; P < .001) decreases across groups. Conclusions and Relevance: This study found that the COVID-19 pandemic was associated with immediate decreases in filled buprenorphine prescriptions by members of racial and ethnic minority groups but not White individuals. These findings suggest that members of racial and ethnic minority groups had larger losses in buprenorphine access during the pandemic across payer types.


Assuntos
Buprenorfina , COVID-19 , Idoso , Buprenorfina/uso terapêutico , COVID-19/tratamento farmacológico , Estudos Transversais , Etnicidade , Humanos , Medicare , Grupos Minoritários , Naltrexona/uso terapêutico , Pandemias , Prescrições , Estados Unidos/epidemiologia
14.
Einstein (Sao Paulo) ; 20: eAO5587, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35649051

RESUMO

OBJECTIVE: To evaluate the effects of combining topiramate, bupropion and naltrexone in obesity-induced rats on their weight and subcutaneous adipose tissue. METHODS: A total of 40 male Wistar rats were induced to obesity for 8 weeks and the animals were divided into 8 groups: Ctr - control, G0 - Sham, G1 - oral saline solution (1.0mL/day), G2 - topiramate (20.0mg/kg) and bupropion (5.0mg/kg), G3 - naltrexone (20.0mg/kg), G4 - topiramate (20.0mg/kg), G5 - bupropion (5.0mg/kg) and G6 - topiramate (20.0mg/kg), bupropion (5.0mg/kg) and naltrexone (20.0mg/kg). During the experiment, all animals were weighed weekly. After 30 days of treatment animals were euthanized and their skin fragments were processed and stained with hematoxylin and eosin for morphological, morphometric and biochemical analyzes. RESULTS: The only group that presented a decrease in the volume of subcutaneous adipose tissue was G3, but this decrease was not significant when compared with the other groups. The G4, the G5 and the G6 presented increased adipose tissue volume. Data showed that until the eighth week all animals increased their weight by approximately 50%. After treatment animals of all groups, except G3, increased their weight from 4% to 9% approximately. The G3 was the only group that lost weight, but this decrease was not significant. CONCLUSION: The medicines studied were not efficient in reducing weight in obese rats. However, it should be considered that 30-day treatment period is not enough to observe the stronger effects of these drugs.


Assuntos
Bupropiona , Naltrexona , Animais , Bupropiona/farmacologia , Bupropiona/uso terapêutico , Humanos , Masculino , Naltrexona/farmacologia , Naltrexona/uso terapêutico , Obesidade/tratamento farmacológico , Ratos , Ratos Wistar , Gordura Subcutânea , Topiramato/farmacologia , Topiramato/uso terapêutico
15.
J Drugs Dermatol ; 21(6): 671-673, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35674753

RESUMO

Lichen planopilaris (LPP) is a cicatricial alopecia that presents with patchy or diffuse hair loss at the vertex or parietal scalp. The literature has limited evidence on treatments for this challenging disease, with most reports involving small groups of patients with varied or suboptimal clinical responses. Amongst individuals who do respond to therapy and eventually achieve disease remission, hair regrowth within scarred alopecic patches is rare.1 Herein, we report a patient with biopsy confirmed LPP who demonstrated remarkable hair regrowth at a previously scarred alopecic patch after initiating low-dose naltrexone (LDN) and platelet-rich plasma (PRP), despite minimal response to 4 months of prior therapy with intralesional corticosteroids, topical clobetasol, topical minoxidil, finasteride, doxycycline, and ketoconazole shampoo. This case highlights the importance of remaining flexible and diligent in therapeutic approaches to LPP and the need for more robust literature on prognosis and treatment options for LPP patients. J Drugs Dermatol. 2022;21(6):671-673. doi:10.36849/JDD.6810.


Assuntos
Alopecia em Áreas , Líquen Plano , Plasma Rico em Plaquetas , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Cicatriz/patologia , Humanos , Líquen Plano/diagnóstico , Líquen Plano/tratamento farmacológico , Líquen Plano/patologia , Naltrexona/uso terapêutico
16.
Am J Vet Res ; 83(6)2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35524961

RESUMO

OBJECTIVE: To compare ketamine-butorphanol-azaperone-medetomidine (KBAM) to detomidine-etorphine-acepromazine (DEA) for field anesthesia in captive Przewalski horses (Equus przewalskii). ANIMALS: 10 adult Przewalski horses. PROCEDURES: A prospective randomized crossover trial was conducted. Each horse was immobilized once with KBAM (200 mg ketamine, 109.2 mg butorphanol, 36.4 mg azaperone, and 43.6 mg medetomidine) and once with DEA (40 mg detomidine premedication, followed 20 minutes later by 3.9 to 4.4 mg etorphine and 16 to 18 mg acepromazine). Both protocols were administered by IM remote dart injection with a washout period of 6 months between treatments. Selected cardiorespiratory variables and quality of anesthesia were recorded. Antagonists were administered IM (KBAM, 215 mg atipamezole and 50 mg naltrexone; DEA, 4 mg RX821002 and 100 mg naltrexone). RESULTS: All horses were anesthetized and recovered uneventfully. Inductions (DEA, 6.8 min; KBAM, 11.6 min; P = 0.04) and recoveries (DEA, 3.2 min; KBAM, 19.6 min; P < 0.01) were faster with DEA compared with KBAM. Quality scores for induction and recovery did not differ between protocols, but maintenance quality was poorer for DEA (P < 0.01). Clinical concerns during DEA immobilizations included apnea, severe hypoxemia (arterial partial pressure of oxygen < 60 mm Hg), muscle rigidity, and tremors. Horses treated with KBAM were moderately hypoxemic, but arterial partial pressures of oxygen were higher compared with DEA (P < 0.01). CLINICAL RELEVANCE: Captive Przewalski horses are effectively immobilized with KBAM, and this protocol results in superior muscle relaxation and less marked hypoxemia during the maintenance phase, but slower inductions and recoveries, compared with DEA.


Assuntos
Anestesia , Ketamina , Acepromazina/farmacologia , Anestesia/veterinária , Animais , Azaperona/farmacologia , Butorfanol/farmacologia , Etorfina/farmacologia , Frequência Cardíaca , Cavalos , Hipnóticos e Sedativos/farmacologia , Hipóxia/tratamento farmacológico , Hipóxia/veterinária , Imidazóis , Imobilização/métodos , Imobilização/veterinária , Ketamina/farmacologia , Medetomidina/farmacologia , Naltrexona/farmacologia , Oxigênio/farmacologia , Estudos Prospectivos
17.
AAPS PharmSciTech ; 23(5): 143, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578146

RESUMO

The purpose of this work is to explore the effects of novel absorption enhancers on the nasal absorption of nalmefene hydrochloride (NMF). First, the influence of absorption enhancers with different concentrations and types and drug concentrations on the nasal absorption of NMF was investigated in vivo in rats. The absorption enhancers studied include n-dodecyl-ß-D-maltoside (DDM), hydroxypropyl-ß-cyclodextrin (HP-ß-CD), and polyethylene glycol (15)-hydroxy Stearate (Solutol®HS15). At the same time, the in situ toad palate model and rat nasal mucosa model were used to assess the cilia toxicity. The results showed that all the absorption enhancers investigated significantly promote the nasal absorption of NMF, but with different degrees and trends. Among them, the 0.5% (w/v) DDM had the strongest enhancement effect, followed by 0.5% (w/v) Solutol®HS15, 0.25% (w/v) DDM, 0.25% (w/v) Solutol®HS15, 0.1% (w/v) Solutol®HS15, 0.1% (w/v) DDM, and 0.25% (w/v) HP-ß-CD, with absolute bioavailability of 76.49%, 72.14%, 71.00%, 69.46%, 60.41%, 59.42%, and 55.18%, respectively. All absorption enhancers exhibited good safety profiles in nasal ciliary toxicity tests. From the perspective of enhancing effect and safety, we considered DDM to be a promising nasal absorption enhancer. And in addition to DDM, Solutol®HS15 can also promote intranasal absorption of NMF, which will provide another option for the development of nalmefene hydrochloride nasal spray.


Assuntos
Absorção Nasal , Mucosa Nasal , 2-Hidroxipropil-beta-Ciclodextrina/metabolismo , Administração Intranasal , Animais , Naltrexona/análogos & derivados , Mucosa Nasal/metabolismo , Ratos
18.
JAMA Netw Open ; 5(5): e2213014, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35594048

RESUMO

Importance: Alcohol-associated liver disease (ALD) is one of the most devastating complications of alcohol use disorder (AUD), an increasingly prevalent condition. Medical addiction therapy for AUD may play a role in protecting against the development and progression of ALD. Objective: To ascertain whether medical addiction therapy was associated with an altered risk of developing ALD in patients with AUD. Design, Setting, and Participants: This retrospective cohort study used the Mass General Brigham Biobank, an ongoing research initiative that had recruited 127 480 patients between its start in 2010 and August 17, 2021, when data for the present study were retrieved. The mean follow-up duration from AUD diagnosis was 9.2 years. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes were used to identify ALD and AUD diagnoses. Exposures: Medical addiction therapy was defined as the documented use of disulfiram, acamprosate, naltrexone, gabapentin, topiramate, or baclofen. Patients were considered to be treated if they initiated medical addiction therapy before the relevant outcome. Main Outcomes and Measures: Adjusted odds ratios (aORs) for the development of ALD and hepatic decompensation were calculated and adjusted for multiple risk factors. Results: The cohort comprised 9635 patients with AUD, of whom 5821 were male individuals (60.4%), and the mean (SD) age was 54.8 (16.5) years. A total of 1135 patients (11.8%) had ALD and 3906 patients (40.5%) were treated with medical addiction therapy. In multivariable analyses, medical addiction therapy for AUD was associated with decreased incidence of ALD (aOR, 0.37; 95% CI, 0.31-0.43; P < .001). This association was evident for naltrexone (aOR, 0.67; 95% CI, 0.46-0.95; P = .03), gabapentin (aOR, 0.36; 95% CI, 0.30-0.43; P < .001), topiramate (aOR, 0.47; 95% CI, 0.32-0.66; P < .001), and baclofen (aOR, 0.57; 95% CI, 0.36-0.88; P = .01). In addition, pharmacotherapy for AUD was associated with lower incidence of hepatic decompensation in patients with cirrhosis (aOR, 0.35; 95% CI, 0.23-0.53, P < .001), including naltrexone (aOR, 0.27; 95% CI, 0.10-0.64; P = .005) and gabapentin (aOR, 0.36; 95% CI, 0.23-0.56; P < .001). This association persisted even when medical addiction therapy was initiated only after the diagnosis of cirrhosis (aOR, 0.41; 95% CI, 0.23-0.71; P = .002). Conclusions and Relevance: Results of this study showed that receipt of medical addiction therapy for AUD was associated with reduced incidence and progression of ALD. The associations of individual pharmacotherapy with the outcomes of ALD and hepatic decompensation varied widely.


Assuntos
Alcoolismo , Alcoolismo/complicações , Alcoolismo/epidemiologia , Baclofeno/uso terapêutico , Feminino , Gabapentina , Humanos , Incidência , Cirrose Hepática , Masculino , Pessoa de Meia-Idade , Naltrexona/uso terapêutico , Estudos Retrospectivos , Topiramato/uso terapêutico
19.
Mol Pharm ; 19(7): 2254-2267, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506882

RESUMO

The United States is in the midst of an opioid epidemic that is linked to a number of serious health issues, including an increase in cerebrovascular events, namely, stroke. Chronic prescription opioid use exacerbates the risk and severity of ischemic stroke, contributing to stroke as the fifth overall cause of death in the United States and costing the US health care system over $30 billion annually. Pathologically, opioids challenge the integrity of the blood-brain barrier (BBB), resulting in a dysregulation of tight junction (TJ) proteins that are crucial in maintaining barrier homeostasis. Despite this, treatment options for ischemic stroke are limited, and there are no pharmacological options to attenuate TJ damage, including in incidents that are linked to opioid use. Herein, we have generated carrier-free, pure "nanodrugs" or nanoparticles of naloxone and naltrexone with enhanced therapeutic properties compared to the original (parent) drugs. The generated nanoformulations of both opioid antagonists exhibited successful attenuation of morphine- or oxycodone-induced alterations of TJ protein expression and reduced oxidative stress to a greater extent than the parent drugs (non-nano). As a proof of concept, we then proceeded to evaluate the therapeutic effectiveness of the generated nanodrugs in an ischemic stroke model of mice exposed to morphine or oxycodone. Our results demonstrate that the opioid antagonist nanoformulations reduced stroke severity in mice. Overall, this research implements advances in nanotechnology-based repurposing of FDA-approved therapeutics, and the obtained results also suggest underlying pharmacological mechanisms of opioid antagonists, further supporting these opioid antagonists and their respective nanoformulations as potential therapeutic agents for ischemic stroke.


Assuntos
AVC Isquêmico , Nanopartículas , Transtornos Relacionados ao Uso de Opioides , Acidente Vascular Cerebral , Analgésicos Opioides/uso terapêutico , Animais , AVC Isquêmico/tratamento farmacológico , Camundongos , Morfina/uso terapêutico , Naloxona , Naltrexona , Nanopartículas/uso terapêutico , Antagonistas de Entorpecentes/farmacologia , Antagonistas de Entorpecentes/uso terapêutico , Oxicodona , Acidente Vascular Cerebral/tratamento farmacológico , Proteínas de Junções Íntimas
20.
Drug Alcohol Depend ; 236: 109469, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35605529

RESUMO

BACKGROUND: Methamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUD with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use. METHODS: Secondary analysis of data from a multi-site, open-label, randomized controlled trial of XR-NTX versus BUP-NX for 24 weeks. The outcome variable was MA/A use defined by either positive urine drug toxicology or self-report. The main predictor was treatment assignment (BUP-NX v. XR-NTX). Longitudinal mixed-effects logistic regression models were fit to model the odds of MA/A use during the study. Additional predictors included study visit and baseline MA/A use. RESULTS: Among the sample of 570 participants with OUD, baseline use of MA/A was observed in 105 (18.4%). There was no significant treatment effect over the study period, though BUP-NX subjects, on average, had about half the odds of MA/A use compared to XR-NTX subjects (OR=0.50; p = 0.051). In the same model, baseline MA/A use and study visit were both significantly associated with MA/A use over time. CONCLUSION: In this sample of treated OUD patients, nearly a fifth of participants had MA/A use at baseline and the frequency of use did not decline over time: in fact, the odds of use slightly increased for each later visit. These secondary analyses found no significant difference in MA/A use between BUP-NX and XR-NTX treatment arms, however, the observation of less MA/A in the buprenorphine arm merits further investigation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02032433).


Assuntos
Buprenorfina , Metanfetamina , Transtornos Relacionados ao Uso de Opioides , Buprenorfina/uso terapêutico , Combinação Buprenorfina e Naloxona/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Humanos , Injeções Intramusculares , Metanfetamina/efeitos adversos , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
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