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1.
Clin Drug Investig ; 41(12): 1087-1098, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34784012

RESUMO

BACKGROUND: Transdermal fentanyl is not yet approved for pediatric and adolescent use in Japan. OBJECTIVE: Serum fentanyl concentration and the safety and efficacy of once-a-day fentanyl citrate patch were investigated in pediatric and adolescent patients with cancer pain. METHODS: In this open-label, uncontrolled study, cancer patients aged 2-19 years being treated with strong opioid analgesics were switched to fentanyl citrate patch for 2 weeks. Serum fentanyl concentration was measured at steady state, and severity of pain was evaluated. RESULTS: Eleven patients (four patients aged 2-5 years and seven patients aged 6-19 years) were enrolled. No patient received a dose exceeding 2 mg. Mean serum fentanyl concentrations after administration of 0.5 mg, 1 mg, and 2 mg were 144 pg/mL (n = 4), 277 pg/mL (n = 3), and 2070 pg/mL (n = 4), respectively. All patients were included in the efficacy and safety analysis, but one patient was excluded from the pharmacokinetic analysis because blood was sampled on the day after blood transfusion. A subgroup analysis showed that the mean serum fentanyl concentration tended to be higher in pre-school patients (aged 2-5 years) than in school-aged and adolescent patients (aged 6-19 years) and than in reports of adult patients (aged 20 years and above) who received the same dose. No respiratory adverse events were observed, and pain was well controlled. CONCLUSION: Fentanyl citrate patch tended to result in a higher serum fentanyl concentration in pre-school patients than in school-aged, adolescent, and adult patients who received the same dose. The patch provided adequate pain control, was well tolerated, and did not cause respiratory adverse events. TRIAL REGISTRATION NUMBER: JPRN-JapicCTI-183909.


Assuntos
Dor do Câncer , Neoplasias , Administração Cutânea , Adolescente , Adulto , Analgésicos Opioides/efeitos adversos , Dor do Câncer/tratamento farmacológico , Criança , Fentanila/efeitos adversos , Humanos , Japão , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Dor/diagnóstico , Dor/tratamento farmacológico
2.
Medicine (Baltimore) ; 100(42): e27409, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34678869

RESUMO

INTRODUCTION: The comparison of ketamine with fentanyl for pain control of pediatric orthopedic emergencies remains controversial. We conduct a systematic review and meta-analysis to explore the influence of ketamine versus fentanyl on pain management among pediatric orthopedic emergencies. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2020 for randomized controlled trials assessing the effect of ketamine versus fentanyl on pain management for pediatric orthopedic emergencies. RESULTS: Five randomized controlled trials are included in the meta-analysis. Overall, compared with fentanyl for pediatric orthopedic emergencies, ketamine led to similar change in pain scores at 15 to 20 minutes (standard mean difference = -0.05; 95% confidence interval [CI] = -0.38 to 0.28; P = .77) and 30 minutes (standard mean difference = 0.11; 95% CI = -0.20 to 0.42; P = .49), as well as rescue analgesia (RR = 0.90; 95% CI = 0.54 to 1.51; P = .69), but revealed the increase in nausea/vomiting (RR = 2.65; 95% CI = 1.13 to 6.18; P = .02) and dizziness (RR = 3.83; 95% CI = 1.38 to 10.60; P = .01). CONCLUSIONS: Ketamine may be similar to fentanyl in terms of the analgesic efficacy for pediatric orthopedic emergencies.


Assuntos
Emergências , Fentanila/uso terapêutico , Ketamina/uso terapêutico , Ortopedia/métodos , Dor/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Vias de Administração de Medicamentos , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Lactente , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Manejo da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Drug Alcohol Depend ; 227: 108974, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34492557

RESUMO

BACKGROUND: High doses of the synthetic opioid fentanyl cause rapid and sustained vocal cord closure (VCC) leading to airway obstruction that prevents overdose victims from breathing. This airway effect is not caused by morphine-derived opiates (e.g. heroin), is distinct from respiratory depression, resistant to naloxone, and can be lethal. However, VCC has not been previously included in animal models of opioid overdose. METHODS: Video laryngoscopy was used to monitor vocal cord movement in anesthetized Sprague-Dawley rats. Rats were administered saline, fentanyl (5, 25, or 50 µg/kg) or morphine (5 mg/kg) in an intravenous (IV) bolus delivered over a 10 s period. The mu opioid receptor (MOR) antagonist naloxone was administered as a pre-treatment (1 mg/kg, IV) 5 min prior to fentanyl (25 µg/kg) or a post-treatment (1 and 2 mg/kg) 1 min after fentanyl (25 µg/kg). RESULTS: Fentanyl (25 and 50 µg/kg) caused sustained and lethal VCC within 10 s. Morphine (5 mg/kg) and fentanyl (5 µg/kg) caused only brief laryngospasm with full recovery. Pre-treatment with naloxone (1 mg/kg) prevented fentanyl-induced VCC, but naloxone (1 and 2 mg/kg) was unable to reverse VCC when administered after fentanyl. CONCLUSIONS: These results indicate sustained VCC is a lethal physiological reaction, specific to fentanyl and resistant to naloxone treatment. While pre-treatment with naloxone prevented fentanyl-induced VCC, naloxone was unable to reverse the effect, suggesting a non-opioid receptor-mediated mechanism. These findings demonstrate the necessity of VCC inclusion in animal models of synthetic opioid overdose and the urgent need for more effective treatments for fentanyl-related overdoses.


Assuntos
Overdose de Drogas , Overdose de Opiáceos , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Animais , Overdose de Drogas/tratamento farmacológico , Fentanila/efeitos adversos , Fentanila/uso terapêutico , Naloxona/farmacologia , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/farmacologia , Antagonistas de Entorpecentes/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptores Opioides mu , Prega Vocal
4.
J Biomed Sci ; 28(1): 62, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503531

RESUMO

BACKGROUND: One of the most prominent opioid analgesics in the United States is the high potency agonist fentanyl. It is used in the treatment of acute and chronic pain and as an anesthetic adjuvant. When used inappropriately, however, ingestion of just a few milligrams of fentanyl or other synthetic opioid can cause opioid-induced respiratory depression (OIRD), often leading to death. Currently, the treatment of choice for OIRD is the opioid receptor antagonist naloxone. Recent reports, however, suggest that higher doses or repeated dosing of naloxone (due to recurrence of respiratory depression) may be required to reverse fully fentanyl-induced respiratory depression, rendering this treatment inadequate. To combat this synthetic opioid overdose crisis, this research aims at identifying a novel opioid reversal agent with enhanced efficacy towards fentanyl and other synthetic opioids. METHODS: A series of naltrexone analogues were characterized for their ability to antagonize the effects of fentanyl in vitro utilizing a modified forskolin-induced cAMP accumulation assay. Lead analogue 29 was chosen to undergo further PK studies, followed by in vivo pharmacological analysis to determine its ability to antagonize opioid-induced antinociception in the hot plate assay. RESULTS: A series of potent MOR antagonists were identified, including the highly potent analogue 29 (IC50 = 2.06 nM). Follow-up PK studies revealed 29 to possess near 100% bioavailability following IP administration. Brain concentrations of 29 surpassed plasma concentrations, with an apparent terminal half-life of ~ 80 min in mice. In the hot plate assay, 29 dose-dependently (0.01-0.1 mg/kg; IP) and fully antagonized the antinociception induced by oxycodone (5.6 mg/kg; IP). Furthermore, the dose of 29 that is fully effective in preventing oxycodone-induced antinociception (0.1 mg/kg) was ineffective against locomotor deficits caused by the KOR agonist U50,488. CONCLUSIONS: Methods have been developed that have utility to identify enhanced rescue agents for the treatment of OIRD. Analogue 29, possessing potent MOR antagonist activity in vitro and in vivo, provides a promising lead in our search for an enhanced synthetic opioid rescue agent.


Assuntos
Analgésicos Opioides/efeitos adversos , Fentanila/efeitos adversos , Naltrexona , Antagonistas de Entorpecentes , Animais , Desenho de Fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naltrexona/síntese química , Naltrexona/farmacocinética , Naltrexona/farmacologia , Antagonistas de Entorpecentes/síntese química , Antagonistas de Entorpecentes/farmacocinética , Antagonistas de Entorpecentes/farmacologia
5.
Ann Palliat Med ; 10(8): 8665-8671, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34379981

RESUMO

BACKGROUND: Bronchoscopic examination including endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is well established for lung cancer diagnosis and staging. Sedation using fentanyl and midazolam is recommended during bronchoscopic examinations. Meanwhile, inadvertent oversedation is a clinical problem. The objective of this research was to estimate the frequency of apnea episodes by end-tidal capnography under fentanyl and midazolam sedation during bronchoscopy. METHODS: Eighty-five patients were enrolled retrospectively between August 2017 and March 2018 at Okayama Medical Center. Apnea was defined as the cessation of airflow for more than 10 seconds. We reviewed medical records, including capnographic data, by cap-ONE YG-227T (NIHON KOHDEN, Tokyo, Japan) during flexible bronchoscopy under fentanyl and midazolam sedation. RESULTS: Patients received 49.4±20.6 µg of fentanyl [mean ± standard deviation (SD)] and 4.35±2.0 mg of midazolam (mean ± SD). The patients included 52 males and 33 females; the median age was 71 (range, 31-88) years were enrolled. Apnea episodes were recorded (median duration 18 seconds) in 85 patients (100%). Prolonged apnea episodes with more than 30 seconds occurred in 56 patients (65.8%). Furthermore, the median time was 32 (range, 5-102) seconds whose delay between the onset of an apnea episode and decline in the SpO2 level of ≥4% from baseline. CONCLUSIONS: End-tidal capnography, cap-ONE YG-227T was effective for detecting the occurrence of apnea in patients undergoing a bronchoscopic examination under fentanyl and midazolam sedation. Monitoring might be useful for preventing inadvertent oversedation.


Assuntos
Broncoscopia , Midazolam , Idoso , Sedação Consciente , Feminino , Fentanila/efeitos adversos , Humanos , Masculino , Midazolam/uso terapêutico , Estudos Retrospectivos
6.
Br J Anaesth ; 127(4): 501-505, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34362559

RESUMO

Intrathecal morphine in combination with fentanyl is an effective and safe alternative to diamorphine for Caesarean delivery analgesia. Evidence suggests minimal differences in clinical efficacy and side-effects between intrathecal morphine and diamorphine. Recommended intrathecal morphine doses for Caesarean delivery analgesia are 100-150 ug.


Assuntos
Analgesia Obstétrica/métodos , Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Morfina/administração & dosagem , Analgesia Obstétrica/efeitos adversos , Analgésicos Opioides/efeitos adversos , Cesárea/métodos , Relação Dose-Resposta a Droga , Medicina Baseada em Evidências , Feminino , Fentanila/efeitos adversos , Heroína/administração & dosagem , Heroína/efeitos adversos , Humanos , Injeções Espinhais , Morfina/efeitos adversos , Gravidez
7.
Ned Tijdschr Geneeskd ; 1652021 08 05.
Artigo em Holandês | MEDLINE | ID: mdl-34351717

RESUMO

Serious complications of drug abuse are frequently seen in acute care. When the clinical signs and symptoms of drug use are discordant with the expected clinical features of the intended substance used, it may involve misleading, contaminated and therefore dangerous illicit drugs. In 2014 and 2015, multiple young patients presented to several Dutch emergency departments in Amsterdam with an opioid toxidrome after supposed use of cocaine. However, it required months and multiple patient presentations, including fatalities, to discover that heroin was sold as cocaine, resulting in serious opioid toxidrome complications. The improvement and formalization of local collaboration and the instatement of an accessible central coordinating party enables early pattern recognition, treatment, sample testing and prevention of future cases of serious drug complications. This was demonstrated in a case of accidental fentanyl intoxication after alleged cocaine use in 2018. Extension of such collaborative networks to create a national coverage is desirable.


Assuntos
Cocaína , Overdose de Drogas , Drogas Ilícitas , Analgésicos Opioides/efeitos adversos , Cocaína/efeitos adversos , Fentanila/efeitos adversos , Heroína/efeitos adversos , Humanos , Drogas Ilícitas/efeitos adversos
8.
J Interv Cardiol ; 2021: 9932171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34404983

RESUMO

Objective: We aimed to study the differences in perception of pain during cardiac catheterization with midazolam monotherapy compared to the current standard of midazolam plus fentanyl. Background: Procedural sedation is important to ensure comfort and safety in patients undergoing left heart catheterization. Despite the widespread use of midazolam and fentanyl for procedural sedation, the effectiveness of this dual agent approach to sedation has never been studied in comparison to midazolam monotherapy. Methods: A total of 129 patients undergoing sedation for outpatient elective cardiac catheterization were randomly assigned to either midazolam monotherapy (n = 69) or combination of midazolam and fentanyl (n = 60). The primary outcome was assessment of pain perception prior to discharge by patient completion of a pain questionnaire. Participants were asked if they experienced any pain during their procedure (yes/no) and, if yes, asked to rate their overall pain level using a 10-point Likert scale that ranged from 1 (minimal pain) to 10 (worst pain imaginable). Results: Most patients (n = 94, 73%) reported no pain during their procedure. Patients sedated with midazolam monotherapy reported similar average pain scores compared to patients sedated with the combination of midazolam and fentanyl (1.1 vs. 1.1, p=0.95). Conclusions: Among patients undergoing elective cardiac catheterization, no significant differences in pain scores were noted between sedation with midazolam alone compared to midazolam and fentanyl. Due to fentanyl's unfavorable interaction with P2Y12 agents, increased costs, and addiction potential, it is imperative that cardiologists revisit the role of effective procedural sedation with a single agent and avoid the use of fentanyl.


Assuntos
Cateterismo Cardíaco , Fentanila , Hipnóticos e Sedativos , Midazolam , Idoso , Cateterismo Cardíaco/efeitos adversos , Sedação Consciente/efeitos adversos , Feminino , Fentanila/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Midazolam/efeitos adversos , Pessoa de Meia-Idade
9.
J Investig Med High Impact Case Rep ; 9: 23247096211034036, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34301155

RESUMO

Wooden chest syndrome (WCS) describes a finding of fentanyl-induced skeletal muscle rigidity causing ventilatory failure. Known primarily to anesthesiology, pulmonary, and critical care fields, WCS is a rare complication that may affect patients of all ages if exposed to intravenous fentanyl, characterized by a patient's inability to properly ventilate. Given the rise of synthetic opioid deaths across the United States in the past decade, an understanding of all of fentanyl's effects on the body is necessary. In this article, we present a case of WCS in a patient with acute respiratory distress syndrome in a 61-year-old female.


Assuntos
Insuficiência Respiratória , Parede Torácica , Analgésicos Opioides/efeitos adversos , Feminino , Fentanila/efeitos adversos , Humanos , Pessoa de Meia-Idade , Rigidez Muscular/induzido quimicamente
10.
Emerg Med Clin North Am ; 39(3): 677-687, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34215409

RESUMO

In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic and several emerging opioids, including buprenorphine, loperamide, fentanyl, fentanyl derivatives, and others. Kratom, a plant occasionally used for opiate detoxification, along with the sedatives etizolam and phenibut, will be discussed. Lastly, this article discusses the phenethylamines and marijuana.


Assuntos
Drogas Desenhadas/efeitos adversos , Drogas Ilícitas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Buprenorfina/administração & dosagem , Buprenorfina/efeitos adversos , Canabinoides/efeitos adversos , Drogas Desenhadas/administração & dosagem , Overdose de Drogas/tratamento farmacológico , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Loperamida/administração & dosagem , Loperamida/efeitos adversos , Mitragyna/efeitos adversos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Fenetilaminas/efeitos adversos
11.
Clin Ter ; 172(4): 271-272, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34247209

RESUMO

Abstract: Currently, the world is facing an unprecedent change of everyday life, due to the Covid-19 pandemic that has been affecting all the nations for more than one year. The public health systems were restructured in all the countries as a response to the constant emergency status, ne-glecting some services like toxicological analyses. In this scenario, the current spread of the New Psychoactive Substances is less controlled than before and the data on its expected mutation come from seizures analyses. Where the global distribution of drugs of abuse was affected by the restriction, fentanyl seizures did not drop during the pandemic. Moreover, new synthesis of fentanyl analogues resulted in new toxic adulterants as by products. Furthermore, diversion of benzodiazepines and new designer benzodiazepines were reported during the pandemic period. In this scenario, the scientific community and the international agencies should tighten their collaboration in order to monitor the emerging of new unknown substances.


Assuntos
Benzodiazepinas/efeitos adversos , COVID-19/epidemiologia , Contaminação de Medicamentos/estatística & dados numéricos , Fentanila/efeitos adversos , Psicotrópicos/efeitos adversos , Saúde Pública/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Humanos , Pandemias , SARS-CoV-2
12.
Medicine (Baltimore) ; 100(26): e26438, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190167

RESUMO

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complaint in patients following general anesthesia. Various antiemetics, including 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, are effective but still have limited efficacy. Therefore, combination therapy is preferable to using a single drug alone in high-risk patients. We performed a comparative study on the antiemetic effect of palonosetron, a 5-HT3 receptor antagonist, monotherapy vs palonosetron-midazolam combination therapy for the prevention of PONV. METHODS: A total of 104 female patients scheduled for breast cancer surgery were enrolled. They were randomly divided into 2 groups, a palonosetron monotherapy group (group P) and palonosetron-midazolam combination therapy group (group PM). Both groups received 0.075 mg palonosetron intravenously after induction of anesthesia. Patient-controlled analgesia (PCA) was applied according to the allocated group. Intravenous (IV)-PCA in group P consisted of fentanyl 20 µg/kg plus normal saline (total volume: 100 ml); IV-PCA in group PM consisted of fentanyl 20 µg/kg plus midazolam 4 mg plus normal saline (total volume: 100 ml). Efficacy parameters were collected during 0 to 1, 1 to 6, 6 to 24, and 24 to 48 hours postoperative time intervals. These measures included complete response (defined as no PONV and no rescue anti-emetic use) rate, incidence of PONV, sedation score, rescue antiemetic use, rescue analgesic use, and numerical rating scale (NRS) for pain. The complete response rate during the 0 to 24 hours interval was analyzed as the primary outcome. RESULTS: Although the complete response rate between 0 and 24 hours was higher in group PM (42.3% and 48.1% in group P and PM, respectively), there was no statistically significant difference (P = .55). The complete response rates in other time intervals were not different between the 2 groups as well. The sedation score and NRS score also showed no differences between the 2 groups. CONCLUSIONS: The combination therapy of palonosetron with midazolam did not lead to a greater reduction in the incidence of PONV than monotherapy in patients undergoing breast surgery and receiving IV-PCA containing fentanyl.


Assuntos
Analgesia Controlada pelo Paciente/efeitos adversos , Neoplasias da Mama/cirurgia , Fentanila , Midazolam/administração & dosagem , Palonossetrom/administração & dosagem , Náusea e Vômito Pós-Operatórios , Anestésicos Intravenosos/administração & dosagem , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/métodos , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Mastectomia/efeitos adversos , Mastectomia/métodos , Midazolam/efeitos adversos , Pessoa de Meia-Idade , Palonossetrom/efeitos adversos , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Resultado do Tratamento
13.
Int J Drug Policy ; 95: 103303, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34112568

RESUMO

BACKGROUND: Although toxicologists, medical professionals, and service providers have determined that the risk of overdose from fentanyl exposure is extremely low for law enforcement and other first responders, hundreds of media and social media accounts contradict these facts, making these civil servants unnecessarily concerned about such occupational hazards. METHODS: We conducted a qualitative study to explore knowledge and fear of fentanyl exposure by interviewing 23 law enforcement leaders and officers in five diverse law enforcement agencies in the United States. RESULTS: Nearly all leaders and officers interviewed wrongly believed that dermal exposure to fentanyl was deadly and expressed fear about such exposure on scene. Officers had a lack of education about fentanyl exposure and faulty or dubious sources of information about it. CONCLUSION: There is a substantial, pressing need for dissemination of research about the lack of overdose risk associated with dermal fentanyl exposure through channels that law enforcement trust, including through basic academy, in-service training, and law enforcement bulletins and newsletters.


Assuntos
Overdose de Drogas , Socorristas , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/epidemiologia , Fentanila/efeitos adversos , Humanos , Aplicação da Lei , Polícia , Estados Unidos
14.
Bioorg Med Chem ; 41: 116225, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34034147

RESUMO

Unintentional overdose deaths related to opioids and psychostimulants have increased in prevalence due to the adulteration of these drugs with fentanyl. Synergistic effects between illicit compounds and fentanyl cause aggravated respiratory depression, leading to inadvertent fatalities. Traditional small-molecule therapies implemented in the expanding opioid epidemic present numerous problems since they interact with the same opioid receptors in the brain as the abused drugs. In this study, we report an optimized dual hapten for use as an immunopharmacotherapeutic tool in order to develop antibodies capable of binding to fentanyl-contaminated heroin in the periphery, thus impeding the drugs' psychoactive effects on the central nervous system. This vaccine produced antibodies with nanomolar affinities and effectively blocked opioid analgesic effects elicited by adulterated heroin. These findings provide further insight into the development of chemically contiguous haptens for broad-spectrum immunopharmacotherapies against opioid use disorders.


Assuntos
Overdose de Drogas/prevenção & controle , Fentanila/imunologia , Haptenos/imunologia , Heroína/efeitos adversos , Heroína/química , Vacinas/imunologia , Animais , Contaminação de Medicamentos , Overdose de Drogas/mortalidade , Fentanila/efeitos adversos , Fentanila/química , Humanos , Camundongos , Transtornos Relacionados ao Uso de Opioides
15.
J Subst Abuse Treat ; 125: 108313, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34016300

RESUMO

BACKGROUND: Standard public health approaches to risk communication do not address the gendered dynamics of drug use. The aim of this study was to explore perceptions of fentanyl-related risks among women and men to inform future risk communication approaches. METHODS: We conducted a qualitative study, purposively sampling English-speaking women and men, aged 18-25 or 35+ years, with past 12-month illicitly manufactured fentanyl use. In-depth individual interviews explored experiences of women and men related to overdose and fentanyl use. We conducted a grounded content analysis examining specific codes related to overdose and other health or social risks attributed to drug use. Using a constant comparison technique, we explored commonalities and differences in themes between women and men. RESULTS: The study enrolled twenty-one participants, 10 women and 11 men. All participants had personal overdose experiences. Both women and men described overdosing as a "chronic" condition and expressed de-sensitization to the risk of overdose. Women and men described other risks around health, safety, and state services that often superseded their fear of overdose. Women feared physical and sexual violence and prioritized caring for children and maintaining relations with child protective services, while men feared violence arising from obtaining and using street drugs and incarceration. Only women reported that fear of violence prevented their utilization of harm reduction services. CONCLUSIONS: Experiences with overdose and risk communication among people who use fentanyl-containing opioids varied by gender. The development of gender-responsive programs that address targeted concerns may be an avenue to enhance engagement with harm reduction and treatment services and create safe spaces for women not currently accessing available services.


Assuntos
Overdose de Drogas , Drogas Ilícitas , Adolescente , Adulto , Analgésicos Opioides/efeitos adversos , Criança , Overdose de Drogas/tratamento farmacológico , Feminino , Fentanila/efeitos adversos , Redução do Dano , Humanos , Masculino , Adulto Jovem
16.
Eur J Pharmacol ; 903: 174132, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33933466

RESUMO

Opioid-induced constipation is the most prevalent adverse effect of opioid drugs. Peripherally acting mu opioid receptor antagonists (PAMORAs), including naloxegol, are indicated for the treatment of opioid-induced constipation. The aim of this study was the in vitro and in vivo pharmacological characterization of naloxegol in comparison with naloxone. In vitro experiments were performed to measure calcium mobilization in cells coexpressing opioid receptors and chimeric G proteins and mu receptor interaction with G protein and ß-arrestin 2 using bioluminescence resonance energy transfer. In vivo experiments were performed in mice to measure pain threshold using the tail withdrawal assay and colonic transit using the bead expulsion assay. In vitro, naloxegol behaved as a selective and competitive mu receptor antagonist similarly to naloxone, being 3-10-fold less potent. In vivo, naloxone was effective in blocking fentanyl actions when given subcutaneously (sc), but not per os (po). In contrast, naloxegol elicited very similar effects with sc or po administration counteracting in a dose dependent manner the constipating effects of fentanyl without interfering with the fentanyl mediated analgesia. Thus, a useful PAMORA action could be obtained with naloxegol both after po and sc administration.


Assuntos
Constipação Intestinal/tratamento farmacológico , Morfinanos/farmacologia , Antagonistas de Entorpecentes/farmacologia , Polietilenoglicóis/farmacologia , Administração Oral , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Células CHO , Cálcio/metabolismo , Constipação Intestinal/induzido quimicamente , Cricetulus , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Fentanila/farmacologia , Injeções Subcutâneas , Masculino , Camundongos , Morfinanos/administração & dosagem , Morfina/farmacologia , Naloxona/administração & dosagem , Naloxona/farmacologia , Antagonistas de Entorpecentes/administração & dosagem , Dor/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Receptores Opioides mu/antagonistas & inibidores , Receptores Opioides mu/efeitos dos fármacos
17.
J Med Chem ; 64(11): 7555-7564, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34008968

RESUMO

RFamide-related peptide-3 (RFRP-3) and neuropeptide FF (NPFF) target two different receptor subtypes called neuropeptide FF1 (NPFF1R) and neuropeptide FF2 (NPFF2R) that modulate several functions. However, the study of their respective role is severely limited by the absence of selective blockers. We describe here the design of a highly selective NPFF1R antagonist called RF3286, which potently blocks RFRP-3-induced hyperalgesia in mice and luteinizing hormone release in hamsters. We then showed that the pharmacological blockade of NPFF1R in mice prevents the development of fentanyl-induced hyperalgesia while preserving its analgesic effect. Altogether, our data indicate that RF3286 represents a useful pharmacological tool to study the involvement of the NPFF1R/RFRP-3 system in different functions and different species. Thanks to this compound, we showed that this system is critically involved in the development of opioid-induced hyperalgesia, suggesting that NPFF1R antagonists might represent promising therapeutic tools to improve the use of opioids in the treatment of chronic pain.


Assuntos
Analgésicos Opioides/efeitos adversos , Dipeptídeos/química , Receptores de Neuropeptídeos/antagonistas & inibidores , Animais , Cricetinae , Dipeptídeos/metabolismo , Dipeptídeos/farmacologia , Dipeptídeos/uso terapêutico , Feminino , Fentanila/efeitos adversos , Meia-Vida , Humanos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hormônio Luteinizante/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuropeptídeos/química , Neuropeptídeos/metabolismo , Neuropeptídeos/farmacologia , Neuropeptídeos/uso terapêutico , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Receptores de Neuropeptídeos/metabolismo , Receptores Opioides/química , Receptores Opioides/metabolismo , Relação Estrutura-Atividade
18.
Soc Sci Med ; 279: 113986, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33971445

RESUMO

The practice of prescription opioid (PO) diversion remains highly controversial and has been characterized as a source of significant drug-related harm by physicians and public health officials. We critically analyze the "problem" of diversion through an examination of the perspectives of people who divert POs during an overdose epidemic to better understand the practice, including benefits and challenges, as well as how diversion is shaped by structural contexts. Qualitative semi-structured interviews were conducted with 21 participants recruited from ongoing cohort studies involving people who use drugs in Vancouver, Canada. Prohibitive prescribing policies made accessing POs difficult, leading some to smuggle drugs out of clinics. Others would buy POs in bulk or do trades to acquire them. Participants risked having their prescriptions terminated, but rationalized this risk as a protective measure that allows them to provide safer drugs to others (e.g., to prevent overdose or treat withdrawal). Poverty also framed diversion, with some participants diverting their POs to generate income to pay for expenses including food and sometimes illicit fentanyl (perceived as a stronger alternative). However, diversion was shaped by other constraints, including criminalization, negative health impacts from not consistently consuming POs, and supplies running out, which led some participants to rely on other illegal means to generate income. This study highlights the intricate means by which POs are acquired and diverted and how environmental contexts frame how participants negotiated risk and rationalized diversion. Our study provides an alternative perspective on the "problem" of diversion and demonstrate a positive effect in providing a safer drug supply to others during an overdose crisis. Given that drug policy, criminalization, and poverty created challenges, our findings demonstrate the need for strategies that engender greater safety, reduce harm, and alleviate the effects of these constraints, including through policies promoting safer drug supplies, decriminalization, and employment.


Assuntos
Overdose de Drogas , Epidemias , Analgésicos Opioides/efeitos adversos , Canadá , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/epidemiologia , Overdose de Drogas/prevenção & controle , Fentanila/efeitos adversos , Humanos , Prescrições
20.
J Forensic Sci ; 66(4): 1186-1200, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33951192

RESUMO

Fentanyl is now the primary driver of the current opioid crisis. Fentanyl and its analogues are subject to the Controlled Substances Act of 1970, the Controlled Substances Analogue Enforcement Act of 1986 (Federal Analogue Act), state laws, international treaties, and the laws of foreign countries. The appearance of novel psychoactive substances led to further legislative developments in scheduling. New fentanyl analogues proliferated in a manner previously unseen since about 2016. Overdose deaths of these fentanyl analogues prompted the Drug Enforcement Administration to reactively emergency schedule each new fentanyl analogue as it appeared. The international community also acted. Finally, on February 6, 2018, a proactive temporary (emergency) class-wide scheduling of fentanyl-related substances was implemented based upon the fentanyl core structure to save lives. This action spurred a similar action in China. Fentanyl analogues fell dramatically in the marketplace, despite further increases in fentanyl itself. Congress temporarily extended this scheduling, but it will soon expire. Opposition to permanent class-wide was lodged due to concerns over law enforcement overreach, inadequate Health and Human Services input, and hindrance of research. This paper reaffirms the importance of a class-based scheduling strategy while also arguing for increased research of schedule I controlled substances.


Assuntos
Analgésicos Opioides/efeitos adversos , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , Fentanila/análogos & derivados , Fentanila/efeitos adversos , Humanos , Drogas Ilícitas/efeitos adversos , Epidemia de Opioides , Estados Unidos
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