Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 858
Filtrar
1.
Anesth Analg ; 132(2): 406-419, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33332902

RESUMO

A serious adverse effect of prescription opioid analgesics is addiction, both to these analgesics and to illicit drugs like heroin that also activate the µ-opioid receptor (MOR). Opioid use disorder (OUD) and opioid overdose deaths represent a current American health crisis, and the prescription of opioid analgesics has contributed significantly to this crisis. While prescription opioids are highly effective analgesics, there currently exists no facile way to use them for extended periods without the risk of addiction. If addiction caused by MOR-targeting analgesics could be blocked by blending in a new "antiaddiction" ingredient that does not diminish analgesia and does not introduce its own therapeutically limiting side effects, then continued clinical use of prescription opioids for treating pain could be maintained (or even enhanced) instead of curtailed. In this narrative review, we contextualize this hypothesis, first with a brief overview of the current American opioid addiction crisis. The neurobiology of 2 key receptors in OUD development, MOR and the κ-opioid receptor (KOR), is then discussed to highlight the neuroanatomical features and circuitry in which signal transduction from these receptors lie in opposition-creating opportunities for pharmacological intervention in curtailing the addictive potential of MOR agonism. Prior findings with mixed MOR/KOR agonists are considered before exploring new potential avenues such as biased KOR agonists. New preclinical data are highlighted, demonstrating that the G protein-biased KOR agonist nalfurafine reduces the rewarding properties of MOR-targeting analgesics and enhances MOR-targeting analgesic-induced antinociception. Finally, we discuss the recent discovery that a regulator of G protein signaling (namely, RGS12) is a key component of signaling bias at KOR, presenting another drug discovery target toward identifying a single agent or adjuvant to be added to traditional opioid analgesics that could reduce or eliminate the addictive potential of the latter drug.


Assuntos
Desenho de Fármacos , Antagonistas de Entorpecentes/farmacologia , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Receptores Opioides kappa/agonistas , Receptores Opioides mu/agonistas , Animais , Humanos , Estrutura Molecular , Antagonistas de Entorpecentes/efeitos adversos , Antagonistas de Entorpecentes/química , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/psicologia , Transtornos Relacionados ao Uso de Opioides/etiologia , Proteínas RGS/metabolismo , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/metabolismo , Transdução de Sinais , Relação Estrutura-Atividade
2.
JAMA Netw Open ; 3(12): e2029676, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33320266

RESUMO

Importance: Whereas outpatient treatment with medication for opioid use disorder (MOUD) is evidence based, there is a large network of inpatient facilities in the US that are reimbursed by commercial insurers and do not typically offer MOUD. Objective: To compare the rates of opioid-related overdose and all-cause hospitalization after outpatient MOUD treatment vs inpatient care. Design, Setting, and Participants: This comparative effectiveness research study used deidentified claims of commercially insured individuals in the US from the MarketScan Commercial Claims and Encounters Database from January 1, 2010, to December 31, 2017, to obtain a sample of 37 090 individuals with opioid use disorder who initiated treatment with inpatient care and/or MOUD. Data were analyzed from October 1, 2019, to May 1, 2020. To address nonrandom treatment assignment, individuals with opioid use disorder who initiated MOUD or who entered inpatient care were matched 1:1 based on propensity scores. Exposures: The independent variable of interest was the type of treatment initiated. Individuals could initiate 1 of 5 potential treatments: (1) outpatient MOUD, (2) short-term inpatient care, (3) short-term inpatient care followed by outpatient MOUD within 30 days, (4) long-term inpatient care, or (5) long-term inpatient care followed by outpatient MOUD within 30 days. Main Outcomes and Measures: Opioid-related overdose and all-cause hospitalization at any point within the 12 months after treatment of opioid use disorder. The hazard for each outcome was estimated using a time-to-event Cox proportional hazards regression model. Results: The cohort included 37 090 individuals matched 1:1 between inpatient and outpatient treatment (20 723 [56%] were younger than 30 years; 23 250 [63%] were male). After propensity score matching, compared with the inpatient treatments, initiation of outpatient MOUD alone was followed by the lowest 1-year overdose rate (2.2 [95% CI, 2.0-2.5] per 100 person-years vs 3.5 [95% CI, 2.7-4.4] to 7.0 [95% CI, 4.6-10.7] per 100 person-years) and hospitalization rate (39 [95% CI, 38-40] per 100 person-years vs 57 [95% CI, 54-61] to 74 [95% CI, 73-76] per 100 person-years). Outpatient MOUD was also associated with the lowest hazard of these events compared with inpatient care, which had hazard ratios ranging from 1.71 (95% CI, 1.35-2.17) to 2.67 (95% CI, 1.68-4.23) for overdose and 1.33 (95% CI, 1.23-1.44) to 1.90 (95% CI, 1.83-1.97) for hospitalizations. Conclusions and Relevance: The results of this comparative effectiveness research study suggest that lower rates of subsequent overdose and hospitalization are associated with outpatient MOUD compared with short- or long-term inpatient care. When patients and clinicians have a choice of treatment, outpatient MOUD treatment may be associated with lower overdose and hospitalization on balance. Future research should assess which patients benefit most from inpatient care and how best to leverage existing inpatient treatment infrastructure.


Assuntos
Buprenorfina , Overdose de Drogas , Hospitalização/estatística & dados numéricos , Pacientes Internados/estatística & dados numéricos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Pacientes Ambulatoriais/estatística & dados numéricos , Adulto , Buprenorfina/administração & dosagem , Buprenorfina/efeitos adversos , Pesquisa Comparativa da Efetividade , Overdose de Drogas/epidemiologia , Overdose de Drogas/etiologia , Overdose de Drogas/terapia , Feminino , Humanos , Masculino , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/efeitos adversos , Avaliação de Processos e Resultados em Cuidados de Saúde
3.
PLoS One ; 15(9): e0238618, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915834

RESUMO

INTRODUCTION: British Columbia's (BC) Take-Home Naloxone (THN) program provides naloxone to bystanders for use in cases of suspected opioid overdose. This study seeks to provide trends and analysis from the provincial BC THN program since inception in 2012 to the end of 2018. MATERIALS AND METHODS: BC THN shipment and distribution records from 2012-2018 were retrieved. Frequency distributions were used to describe characteristics of individuals accessing the program. To evaluate correlates of distribution after the addition of hundreds of pharmacy distribution sites, an analytic sample was limited to records from 2018, and multivariate logistic regression was used to evaluate correlates of collecting naloxone at a pharmacy site. RESULTS: Since program inception to the end of 2018, there were 398,167 naloxone kits shipped to distribution sites, 149,999 kits reported distributed, and 40,903 kits reported used to reverse an overdose in BC. There was a significant increasing trend in the number of naloxone kits used to reverse an overdose over time (p<0.01), and more than 90% of kits that were reported used were distributed to persons at risk of an overdose. Individuals not personally at risk of overdose had higher odds of collecting naloxone at a pharmacy site, compared to other community sites (including harm reduction supply distribution sites, peer led organizations, drop-in centers, and supportive housing sites) (Adjusted Odds Ratio (AOR): 2.69; 95% CI: 2.50-2.90). CONCLUSIONS: This study documents thousands of opioid overdose reversals facilitated through the BC THN program. While those at highest risk of overdose may preferentially access naloxone through community sites, naloxone distribution through pharmacies has allowed the BC THN program to expand dramatically, increasing naloxone availability through longer opening hours on evenings and weekends. and in rural and remote regions. A diversity of naloxone distribution sites and strategies is crucial to prevent rising opioid overdose deaths.


Assuntos
Overdose de Drogas/tratamento farmacológico , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Adulto , Colúmbia Britânica/epidemiologia , Overdose de Drogas/epidemiologia , Overdose de Drogas/prevenção & controle , Feminino , Redução do Dano , Humanos , Masculino , Pessoa de Meia-Idade , Naloxona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Farmácias/tendências
4.
Acta Med Port ; 33(10): 693-702, 2020 Oct 01.
Artigo em Português | MEDLINE | ID: mdl-32705981

RESUMO

INTRODUCTION: The COVID-19 pandemic is a particularly relevant threat to mentally ill patients, and it constitutes a new challenge for health care providers. To the best of our knowledge, there is not any embracing published review about the use of psychotropic drugs during the COVID-19 pandemic. MATERIALS AND METHODS: Non-systematic literature review. A search in the PubMed database was performed, with the terms 'psychotropic drugs', 'COVID-19', 'psychiatry' and 'pandemic'. Consensus and clinical guidelines about psychotropic drugs and COVID-19 approach, published by scientific societies, governmental entities and drug regulatory agencies were included. RESULTS AND DISCUSSION: We present the recommendations about the use of psychotropic drugs during the COVID-19 pandemic, in the outpatient and inpatient settings. The treatment of affective bipolar disorder and schizophrenia have now added increased difficulties. Some psychotropic drugs interfere with the pathophysiology of the novel coronavirus infection and they could interact with the drugs used in the treatment of COVID-19. Some patients will need pharmacological interventions due to the presence of delirium. Smoking cessation changes the serum levels of some psychotropic drugs and may influence their use. CONCLUSION: The COVID-19 pandemic has created new challenges in clinical practice. Psychiatric patients are a vulnerable population and often a careful clinical, laboratorial and electrocardiographic evaluation may be needed, particularly in those diagnosed with COVID-19. The regular treatment of mentally ill patients with COVID-19 presents increased complexity.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transtornos Mentais/tratamento farmacológico , Pneumonia Viral/epidemiologia , Psicotrópicos/uso terapêutico , Antivirais/uso terapêutico , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Regulação da Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/fisiologia , Buprenorfina/efeitos adversos , Buprenorfina/uso terapêutico , Clozapina/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Preparações de Ação Retardada/uso terapêutico , Interações Medicamentosas , Hospitalização , Humanos , Compostos de Lítio/uso terapêutico , Transtornos Mentais/complicações , Metadona/efeitos adversos , Metadona/uso terapêutico , Antagonistas de Entorpecentes/efeitos adversos , Antagonistas de Entorpecentes/uso terapêutico , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Ácido Valproico/uso terapêutico
5.
JAMA ; 323(22): 2310-2328, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515820

RESUMO

Importance: Illicit drug use is among the most common causes of preventable morbidity and mortality in the US. Objective: To systematically review the literature on screening and interventions for drug use to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, Embase, and Cochrane Central Register of Controlled Trials through September 18, 2018; literature surveillance through September 21, 2019. Study Selection: Test accuracy studies to detect drug misuse and randomized clinical trials of screening and interventions to reduce drug use. Data Extraction and Synthesis: Critical appraisal and data abstraction by 2 reviewers and random-effects meta-analyses. Main Outcomes and Measures: Sensitivity, specificity, drug use and other health, social, and legal outcomes. Results: Ninety-nine studies (N = 84 206) were included. Twenty-eight studies (n = 65 720) addressed drug screening accuracy. Among adults, sensitivity and specificity of screening tools for detecting unhealthy drug use ranged from 0.71 to 0.94 and 0.87 to 0.97, respectively. Interventions to reduce drug use were evaluated in 52 trials (n = 15 659) of psychosocial interventions, 7 trials (n = 1109) of opioid agonist therapy, and 13 trials (n = 1718) of naltrexone. Psychosocial interventions were associated with increased likelihood of drug use abstinence (15 trials, n = 3636; relative risk [RR], 1.60 [95% CI, 1.24 to 2.13]; absolute risk difference [ARD], 9% [95% CI, 5% to 15%]) and reduced number of drug use days (19 trials, n = 5085; mean difference, -0.49 day in the last 7 days [95% CI, -0.85 to -0.13]) vs no psychosocial intervention at 3- to 4-month follow-up. In treatment-seeking populations, opioid agonist therapy and naltrexone were associated with decreased risk of drug use relapse (4 trials, n = 567; RR, 0.75 [95% CI, 0.59 to 0.82]; ARD, -35% [95% CI, -67% to -3%] and 12 trials, n = 1599; RR, 0.73 [95% CI, 0.62 to 0.85]; ARD, -18% [95% CI, -26% to -10%], respectively) vs placebo or no medication. While evidence on harms was limited, it indicated no increased risk of serious adverse events. Conclusions and Relevance: Several screening instruments with acceptable sensitivity and specificity are available to screen for drug use, although there is no direct evidence on the benefits or harms of screening. Pharmacotherapy and psychosocial interventions are effective at improving drug use outcomes, but evidence of effectiveness remains primarily derived from trials conducted in treatment-seeking populations.


Assuntos
Programas de Rastreamento/normas , Antagonistas de Entorpecentes/uso terapêutico , Psicoterapia , Detecção do Abuso de Substâncias/normas , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/métodos , Naloxona/efeitos adversos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/efeitos adversos , Guias de Prática Clínica como Assunto , Gravidez , Sensibilidade e Especificidade , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/terapia , Inquéritos e Questionários
6.
JAMA ; 323(22): 2301-2309, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32515821

RESUMO

Importance: An estimated 12% of adults 18 years or older and 8% of adolescents aged 12 to 17 years report unhealthy use of prescription or illegal drugs in the US. Objective: To update its 2008 recommendation, the USPSTF commissioned reviews of the evidence on screening by asking questions about drug use and interventions for unhealthy drug use in adults and adolescents. Population: This recommendation statement applies to adults 18 years or older, including pregnant and postpartum persons, and adolescents aged 12 to 17 years in primary care settings. This statement does not apply to adolescents or adults who have a currently diagnosed drug use disorder or are currently undergoing or have been referred for drug use treatment. This statement applies to settings and populations for which services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred. Evidence Assessment: In adults, the USPSTF concludes with moderate certainty that screening by asking questions about unhealthy drug use has moderate net benefit when services for accurate diagnosis of unhealthy drug use or drug use disorders, effective treatment, and appropriate care can be offered or referred. In adolescents, because of the lack of evidence, the USPSTF concludes that the benefits and harms of screening for unhealthy drug use are uncertain and that the balance of benefits and harms cannot be determined. Recommendation: The USPSTF recommends screening by asking questions about unhealthy drug use in adults 18 years or older. Screening should be implemented when services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred. (Screening refers to asking questions about unhealthy drug use, not testing biological specimens.) (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for unhealthy drug use in adolescents. (I statement).


Assuntos
Programas de Rastreamento/normas , Antagonistas de Entorpecentes/uso terapêutico , Psicoterapia , Detecção do Abuso de Substâncias/normas , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Adulto , Humanos , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/métodos , Antagonistas de Entorpecentes/efeitos adversos , Sensibilidade e Especificidade , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/terapia , Inquéritos e Questionários
7.
Lancet ; 395(10241): 1938-1948, 2020 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-32563380

RESUMO

The treatment of opioid withdrawal is an important area of clinical concern when treating patients with chronic, non-cancer pain, patients with active opioid use disorder, and patients receiving medication for opioid use disorder. Current standards of care for medically supervised withdrawal include treatment with µ-opioid receptor agonists, (eg, methadone), partial agonists (eg, buprenorphine), and α2-adrenergic receptor agonists (eg, clonidine and lofexidine). Newer agents likewise exploit these pharmacological mechanisms, including tramadol (µ-opioid receptor agonism) and tizanidine (α2 agonism). Areas for future research include managing withdrawal in the context of stabilising patients with opioid use disorder to extended-release naltrexone, transitioning patients with opioid use disorder from methadone to buprenorphine, and tapering opioids in patients with chronic, non-cancer pain.


Assuntos
Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Esquema de Medicação , Humanos , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/efeitos adversos
8.
Aliment Pharmacol Ther ; 52(1): 37-53, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32462777

RESUMO

BACKGROUND: When opioid-induced constipation is treated with centrally acting opioid antagonists, there may be opioid withdrawal or aggravation of pain due to inhibition of µ-opioid analgesia. This led to the development of peripherally acting µ-opioid receptor antagonists (PAMORAs). AIM: To evaluate the efficacy of available PAMORAs and other approved or experimental treatments for relieving constipation in patients with opioid-induced constipation, based on a systematic review and meta-analysis of published studies. METHODS: A search of MEDLINE, EMBASE and EBM Reviews Cochrane Central Register of Controlled Trials was completed in July 2019 for randomised trials compared to placebo. FDA approved doses or highest studied dose was evaluated. Efficacy was based on diverse endpoints, including continuous variables (the bowel function index, number of spontaneous bowel movements and stool consistency based on Bristol Stool Form Scale), or responder analysis (combination of >3 spontaneous bowel movements or complete spontaneous bowel movements plus 1 spontaneous bowel movement or complete spontaneous bowel movements, respectively, over baseline [so-called FDA endpoints]). Adverse effects evaluated included central opioid withdrawal, serious adverse events, abdominal pain and diarrhoea. RESULTS: We included 35 trials at low risk of bias enrolling 13 566 patients. All PAMORAs demonstrated efficacy on diverse patient response endpoints. There was greater efficacy with approved doses of the PAMORAs (methylnaltrexone, naloxegol and naldemidine), with lower efficacy or lower efficacy and greater adverse effects with combination oxycodone with naloxone, lubiprostone and linaclotide. CONCLUSIONS: Therapeutic response in opioid-induced constipation is best achieved with the PAMORAs, methylnaltrexone, naloxegol and naldemidine, which are associated with low risk of serious adverse events.


Assuntos
Analgésicos Opioides/efeitos adversos , Constipação Intestinal/tratamento farmacológico , Laxantes/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Receptores Opioides mu/antagonistas & inibidores , Constipação Intestinal/induzido quimicamente , Humanos , Laxantes/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Medicine (Baltimore) ; 99(15): e19781, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282741

RESUMO

INTRODUCTION: Surgical stress and pain are potential provoking factors for postoperative myasthenic crisis (POMC). We report the occurrence of early POMC and late deep vein thrombosis (DVT) in a man with myasthenia gravis (MG) undergoing thymectomy, addressing possible link between reversal of opioid overdose with naloxone and the triggering of POMC. PATIENT CONCERNS: A 71-year-old man with impaired renal function (ie, estimated glomerular filtration rate [egfr]: 49.1 mL/min/1.73 m) with diagnosis of MG made 2 months ago was scheduled for thymectomy. After uncomplicated surgery, he experienced opioid overdose that was treated with naloxone. Hyperlactatemia then developed with a concomitant episode of hypertension. Three hours after reversal, he suffered from myasthenic crisis presenting with respiratory failure and difficult weaning from mechanical ventilation. DIAGNOSIS: Stress-induced hyperlactatemia and subsequent myasthenic crisis INTERVENTIONS:: Pyridostigmine and immunosuppressive therapy with prednisolone were initiated. Hyperlactatemia subsided on postoperative day (POD) 5. Tracheal extubation was performed successfully on POD 6. OUTCOMES: During the course of hospitalization, his eGFR (ie, 88.9 mL/min/1.73 m) was found to improve postoperatively. After discharge from hospital, he developed DVT in the left femoral and popliteal veins on POD 24 when he was readmitted for immediate treatment with low-molecular-weight heparin. He was discharged without sequelae on POD 31. There was no recurrence of myasthenic crisis or DVT at 3-month follow-up. CONCLUSIONS: Following naloxone administration, hyperlactatemia may be an indicator of pain-related stress response, which is a potential provoking factor for myasthenic crisis. Additionally, patients with MG may have an increased risk of DVT possibly attributable to immune-mediated inflammation. These findings highlight the importance of perioperative avoidance of provoking factors including monitoring of stress-induced elevations in serum lactate concentration, close postoperative surveying for myasthenic crisis, and early recognition of possible thromboembolic complications in this patient population.


Assuntos
Miastenia Gravis/complicações , Timectomia/efeitos adversos , Trombose Venosa/etiologia , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hiperlactatemia/induzido quimicamente , Hiperlactatemia/diagnóstico , Hiperlactatemia/tratamento farmacológico , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Miastenia Gravis/diagnóstico , Miastenia Gravis/cirurgia , Naloxona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Brometo de Piridostigmina/administração & dosagem , Brometo de Piridostigmina/uso terapêutico , Respiração Artificial/métodos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Resultado do Tratamento
10.
Mo Med ; 117(1): 59-64, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158052

RESUMO

The opioid crisis has shaped the national public health dialogue for some time now. A "call to action" is a strong and resounding cry from multiple disciplines. This piece intends to detail the nuts and bolts of prescribing medications used for the treatment of opioid use disorder. The underlying message here is that opioid use disorder is a chronic, treatable illness and physicians of all specialties have a responsibility to not turn a blind eye.


Assuntos
Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Buprenorfina/administração & dosagem , Buprenorfina/efeitos adversos , Medicina Baseada em Evidências , Humanos , Metadona/administração & dosagem , Metadona/efeitos adversos , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/efeitos adversos , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Guias de Prática Clínica como Assunto
11.
BMC Gastroenterol ; 20(1): 25, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005157

RESUMO

BACKGROUND: Naldemedine, a novel peripherally-acting mu-opioid receptor antagonist, has improved opioid-induced constipation in randomized controlled trials. The most frequent adverse event of naldemedine is diarrhea, which can cause abdominal pain and often leads to treatment discontinuation. We aimed to identify risk factors and appropriate management strategies for key adverse events including diarrhea associated with naldemedine, since those have not been extensively studied. METHODS: We conducted a multi-center retrospective cohort study. Eligible patients had cancer, had undergone palliative care at participating centers, had been prescribed regular opioids, and had taken at least one dose of naldemedine between June 2017 and March 2018. The primary endpoint was the incidence of diarrhea according to baseline characteristics. Secondary endpoints included the duration of naldemedine administration, daily defecation counts before and after starting naldemedine, duration and severity of diarrhea as an adverse event of naldemedine, other adverse events, and the incidence of constipation within 7 days after recovery from diarrhea. We defined patients who started naldemedine within three days of starting a regularly prescribed opioid as the early group, and the remainder as the late group. RESULTS: Among 103 patients who received naldemedine, 98 fulfilled the eligibility criteria. The median age was 68 years and 48% of the patients were female. Median performance status was 3, and the median oral intake was 50%. The median duration of naldemedine administration and overall survival were 25 and 64 days, respectively. The incidence of diarrhea in the early group (n = 26) was significantly lower than in the late group (n = 72) (3.9% vs. 22.2%, p = 0.02). Daily defecation counts increased after late (median 0.43 to 0.88, p < 0.001), but remained stable after early naldemedine administration (median 1.00 to 1.00, p = 0.34). Constipation after the diarrhea was resolved was common (53%), especially among patients who stopped naldemedine (78%). The diarrhea was improved within three days in 92% of patients who stopped other laxatives. CONCLUSIONS: The early administration of naldemedine is beneficial because it reduces adverse events including diarrhea. Diarrhea caused by naldemedine can be effectively managed by stopping other laxatives while continuing naldemedine.


Assuntos
Analgésicos Opioides/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/prevenção & controle , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/efeitos adversos , Receptores Opioides mu/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/administração & dosagem , Neoplasias/terapia , Cuidados Paliativos , Estudos Retrospectivos
12.
Drugs Aging ; 37(4): 271-279, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32086791

RESUMO

BACKGROUND: Opioid-induced constipation (OIC), the most common side effect of opioid treatment, is under-recognized and undertreated in older patients. Naldemedine, an oral, peripherally acting µ-opioid receptor antagonist (PAMORA), is approved in Japan, the United States, and the European Union for treatment of OIC in adult patients. OBJECTIVE: This integrated analysis of three phase 3 trials (COMPOSE-1, COMPOSE-2, and COMPOSE-3) evaluated the safety and efficacy of naldemedine for up to 12 weeks in a subgroup of patients aged ≥ 65 years. METHODS: Patients aged 18-80 years with chronic non-cancer pain for ≥ 3 months (treated with opioids for ≥ 3 months in COMPOSE-1 and COMPOSE-2) and OIC received oral naldemedine 0.2 mg or placebo once daily. Safety assessments included overall incidence of treatment-emergent adverse events (TEAEs), TEAEs in the gastrointestinal disorders System Organ Class, and TEAEs of opioid withdrawal or possible opioid withdrawal. Efficacy was based on the proportion of responders in COMPOSE-1 and COMPOSE-2, defined as having ≥ 3 spontaneous bowel movements/week and a ≥ 1-spontaneous bowel movement/week increase from baseline for ≥ 9 of 12 weeks and ≥ 3 of the last 4 weeks. RESULTS: A total of 14.8% (344/2328) of patients were aged ≥ 65 years in all studies. The incidence of TEAEs in naldemedine-treated patients aged ≥ 65 years (45.9%) was comparable to that in patients aged ≥ 65 years receiving placebo (51.6%) and in the overall naldemedine group (47.1%). The incidence of gastrointestinal disorders System Organ Class TEAEs in naldemedine-treated patients aged ≥ 65 years (20.2%) was also comparable to that in patients aged ≥ 65 years receiving placebo (16.1%) and in the overall naldemedine group (21.8%). The incidence of TEAEs of opioid withdrawal with naldemedine was 1.1% in patients aged ≥ 65 years and 1.0% overall, and the incidence of TEAEs of possible opioid withdrawal was 1.1% in patients aged ≥ 65 years and 1.7% overall. The proportion of responders was higher in naldemedine-treated patients versus placebo, both overall (50.1% vs 34.1%; p < 0.0001) and in those aged ≥ 65 years (51.8% vs 37.6%). CONCLUSIONS: This integrated analysis confirmed that OIC treatment with naldemedine 0.2 mg was generally well tolerated and effective in patients aged ≥ 65 years with chronic non-cancer pain. Safety and efficacy results were consistent with the overall patient population. CLINICALTRIALS. GOV REGISTRATION: NCT01965158, NCT01993940, NCT01965652.


Assuntos
Dor Crônica/tratamento farmacológico , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/efeitos adversos , Antagonistas de Entorpecentes/uso terapêutico , Constipação Induzida por Opioides/tratamento farmacológico , Segurança , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Naltrexona/efeitos adversos , Naltrexona/uso terapêutico
13.
Mayo Clin Proc ; 95(6): 1253-1267, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32061413

RESUMO

The use of buprenorphine, a mixed opioid agonist-antagonist, for the management of chronic pain and/or opioid use disorder is increasing. As such, medical providers will more frequently encounter patients on this therapy. In this paper, we synthesize existing knowledge (derived through keyword searches using MEDLINE databases) in a novel conceptual framework for patients on buprenorphine presenting with acute pain or for those requiring surgical or invasive procedures. This framework is based on three unique domains: the patient, the features of the acute pain insult, and the environment. We discuss important considerations regarding the unique aspects of buprenorphine formulations and dosing, and we describe the importance of multidisciplinary planning and multimodal analgesic strategies. We also highlight important differences in management strategies based upon the presence or absence of opioid use disorder. All medical providers must be prepared to guide the patient on buprenorphine safely through the acute care episode, which includes adequate treatment of acute pain and avoidance of iatrogenic harm, including both short-term complications (eg, respiratory depression) and long-term complications (eg, relapse to opioid use).


Assuntos
Dor Aguda/tratamento farmacológico , Buprenorfina/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Aguda/complicações , Buprenorfina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Antagonistas de Entorpecentes/administração & dosagem , Tratamento de Substituição de Opiáceos/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Dor Pós-Operatória/complicações
14.
Cutis ; 105(1): E17-E18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32074159

RESUMO

Low-dose naltrexone (LDN) has become a hot topic in many fields of medicine, including dermatology. It has gained popularity as an alternative, off-label treatment that works by targeting inflammation. Patients may ask you about LDN as a treatment option for a variety of inflammatory skin conditions, specifically in comparison to more traditional systemic treatments. It is important for dermatologists to know what LDN is, how it works, how to prescribe it, and what side effects should be monitored.


Assuntos
Inflamação/tratamento farmacológico , Naltrexona/administração & dosagem , Dermatopatias/tratamento farmacológico , Relação Dose-Resposta a Droga , Humanos , Inflamação/patologia , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/efeitos adversos , Uso Off-Label , Dermatopatias/patologia
15.
Annu Rev Pharmacol Toxicol ; 60: 615-636, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31914893

RESUMO

Exposure to stressful stimuli activates kappa opioid receptor (KOR) signaling, a process known to produce aversion and dysphoria in humans and other species. This endogenous opioid system is dysregulated in stress-related disorders, specifically in major depressive disorder (MDD). These findings serve as the foundation for a growing interest in the therapeutic potential of KOR antagonists as novel antidepressants. In this review, data supporting the hypothesis of dysregulated KOR function in MDD are considered. The clinical data demonstrating the therapeutic efficacy and safety of selective and mixed opioid antagonists are then presented. Finally, the preclinical evidence illustrating the induction of behaviors relevant to the endophenotypes of MDD and KOR antagonist activity in stress-naïve and stress-exposed animals is evaluated. Overall, this review highlights the emergent literature supporting the pursuit of KOR antagonists as novel therapeutics for MDD and other stress-related disorders.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Receptores Opioides kappa/antagonistas & inibidores , Estresse Psicológico/tratamento farmacológico , Animais , Transtorno Depressivo Maior/fisiopatologia , Humanos , Antagonistas de Entorpecentes/efeitos adversos , Antagonistas de Entorpecentes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/fisiopatologia
16.
Intern Med ; 59(2): 293-296, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31534081

RESUMO

Opioid-induced-constipation (OIC) can be treated by naldemedine and other peripherally acting mu-opioid receptor antagonists (PAMORA) via a novel mechanism. We describe the case of a 52-year-old female outpatient who developed OIC while receiving oxycodone for pain due to cancer with multiple bone metastases. Although she did not have brain metastasis, opioid withdrawal syndrome (OWS) developed after taking naldemedine orally. Her Clinical Opiate-Withdrawal Score (COWS) was 19 (moderate symptoms). However, she recovered from OWS on intravenous fentanyl and a continuous infusion of oxycodone. She did not develop OWS thereafter and was discharged two days after recovery.


Assuntos
Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/efeitos adversos , Constipação Induzida por Opioides/tratamento farmacológico , Oxicodona/efeitos adversos , Síndrome de Abstinência a Substâncias/etiologia , Analgésicos Opioides/uso terapêutico , Neoplasias da Mama/patologia , Dor do Câncer/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Naltrexona/efeitos adversos , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Oxicodona/uso terapêutico , Síndrome de Abstinência a Substâncias/tratamento farmacológico
17.
Ann Emerg Med ; 75(1): 39-48, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31182316

RESUMO

STUDY OBJECTIVE: We aim to determine whether administration of higher doses of naloxone for the treatment of opioid overdose is associated with increased pulmonary complications. METHODS: This was a retrospective, observational, cross-sectional study of 1,831 patients treated with naloxone by the City of Pittsburgh Bureau of Emergency Medical Services. Emergency medical services and hospital records were abstracted for data in regard to naloxone dosing, route of administration, and clinical outcomes, including the development of complications such as pulmonary edema, aspiration pneumonia, and aspiration pneumonitis. For the purposes of this investigation, we defined high-dose naloxone as total administration exceeding 4.4 mg. Multivariable analysis was used to attempt to account for confounders such as route of administration and pretreatment morbidity. RESULTS: Patients receiving out-of-hospital naloxone in doses exceeding 4.4 mg were 62% more likely to have a pulmonary complication after opioid overdose (42% versus 26% absolute risk; odds ratio 2.14; 95% confidence interval 1.44 to 3.18). This association remained statistically significant after multivariable analysis with logistic regression (odds ratio 1.85; 95% confidence interval 1.12 to 3.04). A secondary analysis showed an increased risk of 27% versus 13% (odds ratio 2.57; 95% confidence interval 1.45 to 4.54) when initial naloxone dosing exceeded 0.4 mg. Pulmonary edema occurred in 1.1% of patients. CONCLUSION: Higher doses of naloxone in the out-of-hospital treatment of opioid overdose are associated with a higher rate of pulmonary complications. Furthermore, prospective study is needed to determine the causality of this relationship.


Assuntos
Analgésicos Opioides/envenenamento , Overdose de Drogas/tratamento farmacológico , Pneumopatias/etiologia , Naloxona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Administração Intranasal/efeitos adversos , Adulto , Estudos de Casos e Controles , Estudos Transversais , Relação Dose-Resposta a Droga , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Estudos Retrospectivos
18.
Am J Emerg Med ; 38(2): 411.e5-411.e6, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31831344

RESUMO

BACKGROUND: In a constantly increasing world of opioid addiction, naloxone has become a topic of great discussion and use. With seemingly minimal side effects, naloxone has become one of the most wellknown and widely used reversal agents for opioid intoxication. While more common effects of using naloxone include agitation, abdominal cramps, piloerection, diarrhea, nausea, and yawning, lesser known side effects involve muscle spasms, flushing, hyperreflexia in neonates, and seizures. This case study demonstrates a side effect of rigidity secondary to IV naloxone that has not previously been documented. CASE: A 56 year old man was brought in by EMS after being found unresponsive in a car with a bag of drugs beside him. He was given 0.5 mg naloxone IV by EMS and immediately brought to the hospital. On arrival, the pt was noted to have tight rigidity of his upper extremities, with severe flexion. This presentation was not noted before the delivery of naloxone by EMS. CONCLUSIONS: While this case highlights a patient with a rare side effect of naloxone, it reminds physicians that all medications come with a cost. Of course, ABCs remain the highest priority of resuscitation, however when administering a medication to reverse a drug overdose, it is important to keep in mind all possible consequences of said agent. Recognizing that complete muscle rigidity may remain a result of naloxone administration allows physicians to perhaps save patients from further medical workup.


Assuntos
Rigidez Muscular/induzido quimicamente , Naloxona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Parede Torácica/fisiopatologia , Adulto , Analgésicos Opioides/efeitos adversos , Serviço Hospitalar de Emergência , Feminino , Humanos , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Síndrome , Parede Torácica/efeitos dos fármacos
19.
Psychopharmacology (Berl) ; 237(3): 855-867, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31832720

RESUMO

RATIONALE: Kratom is proposed to exhibit therapeutic potential as an opium substitute, but little is known about its dependence-producing profile, particularly of its main psychoactive compound, mitragynine (MG). OBJECTIVES: This study examined the dependence-producing effects of MG using operant-scheduled behaviour in rats and investigated the potential therapeutic effect of MG by comparing effects to buprenorphine in morphine-dependent rats using the same schedule-controlled behavioural task. METHODS: The effects of acutely administered MG and morphine were determined in rats trained to respond under fixed-ratio (FR) 10 schedule of food reinforcement. Next, the rats were administered MG and morphine twice daily for 14 consecutive days to determine if physiological dependence would develop by examining cessation of drug treatment and following antagonist-precipitated withdrawal. The study then examined the effects of MG substitution to suppress naloxone-precipitated morphine withdrawal effects on scheduled responding. RESULTS: Acute doses of MG did not produce dose-related decreases on FR schedules of responding compared to morphine. Unlike morphine, MG-treated rats showed no suppression of response rates following cessation of MG treatment. However, withdrawal effects were evident for MG after precipitation by either naloxone or SR141716A (rimonabant), similar to morphine-treated rats. MG in higher doses (10 and 30 mg/kg) attenuated the naloxone-precipitated morphine withdrawal effects while smaller doses of buprenorphine (0.3 and 1.0 mg/kg) were necessary to alleviate these effects. CONCLUSION: The findings suggest that MG does not induce physiological dependence but can alleviate the physical symptoms associated with morphine withdrawal which represent the desired characteristics of novel pharmacotherapeutic interventions for managing opioid use disorder (OUD).


Assuntos
Esquema de Reforço , Reforço Psicológico , Alcaloides de Triptamina e Secologanina/efeitos adversos , Síndrome de Abstinência a Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Animais , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Relação Dose-Resposta a Droga , Masculino , Antagonistas de Entorpecentes/efeitos adversos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
20.
Drug Alcohol Depend ; 207: 107778, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816487

RESUMO

BACKGROUND: Prescription opioid abuse continues to be a public health concern of epidemic proportions. Notwithstanding the extensive literature regarding opioid action, there has been little systematic research regarding the effects of opioid dependence and withdrawal on aspects of cognition-related behavior in laboratory animals. The present studies examined the effects of the prescription opioid oxycodone on learning processes in nonhuman primates. METHODS: The ability of subjects to repeatedly learn novel touchscreen-based visual discriminations was examined during three conditions of opioid exposure. Discrimination learning was examined, first, during oxycodone self-administration (3-hr sessions, 0.1 mg/kg/injection) and, next, during non-contingent chronic treatment with oxycodone (10 mg/kg/day). Finally, discrimination learning was re-examined during antagonist-precipitated opioid withdrawal (0.001-0.1 mg/kg naltrexone) and, subsequently, following abrupt discontinuation of oxycodone treatment. RESULTS: Although motoric behavior was disrupted by oxycodone, neither the development of discrimination learning nor steady-state performance were impaired following oxycodone self-administration or during non-contingent chronic oxycodone treatment. However, discrimination learning was substantially impaired during oxycodone withdrawal, whether elicited by naltrexone or by abrupt oxycodone discontinuation. Moreover, these learning impairments were concordant with autonomic signs of opioid withdrawal. CONCLUSIONS: Taken together, the present studies indicate that impairment of learning processes can accompany the unconditioned signs of opioid withdrawal.


Assuntos
Analgésicos Opioides/administração & dosagem , Aprendizagem por Discriminação/efeitos dos fármacos , Transtornos Relacionados ao Uso de Opioides/psicologia , Oxicodona/administração & dosagem , Síndrome de Abstinência a Substâncias/psicologia , Animais , Aprendizagem por Discriminação/fisiologia , Relação Dose-Resposta a Droga , Masculino , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Oxicodona/efeitos adversos , Primatas , Saimiri , Autoadministração , Síndrome de Abstinência a Substâncias/diagnóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...