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1.
Toxicol Lett ; 320: 109-112, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778775

RESUMO

BACKGROUND: Since 2016 an increase has been observed in the availability of new synthetic opioids (NSO) in Europe. Cyclopropylfentanyl is a very potent and selective µ-opioid agonist, which was reported for the first time in August 2017 in Europe. METHODS: The case was included in a prospective observational study of patients treated in emergency departments after the intake of novel psychoactive substances (NPS). Clinical features were acquired using a structured questionnaire for physicians. Serum and/or urine samples of ED patients were analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) screening methods for NPS. CASE REPORT: Within 10 min after intranasal intake of fentanyl, a 25-year-old male developed nausea, profuse sweating and dyspnoe. Because soon afterwards coma and respiratory insufficiency was noticed, the patient was admitted to hospital. After administration of naloxone (0.8 mg) breathing stabilized. However, the patient displayed recurrent decreases of oxygen saturation for 12 h. The intake of cyclopropylfentanyl was analytically confirmed. CONCLUSION: The constantly growing diversity of NSO still poses a high risk for drug users and can be a challenging task for clinicians and forensic toxicologists. Clinicians treating opioid overdoses should be aware of the potentially long lasting respiratory depression induced by fentanyl analogs.


Assuntos
Analgésicos Opioides/envenenamento , Overdose de Drogas/diagnóstico , Fentanila/análogos & derivados , Transtornos Relacionados ao Uso de Opioides , Detecção do Abuso de Substâncias/métodos , Administração Intranasal , Adulto , Aerossóis , Analgésicos Opioides/administração & dosagem , Cromatografia Líquida de Alta Pressão , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/fisiopatologia , Fentanila/administração & dosagem , Fentanila/envenenamento , Humanos , Masculino , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Resultado do Tratamento
2.
J Opioid Manag ; 15(5): 357-361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849026

RESUMO

OBJECTIVE: To evaluate current practices in naloxone prescribing upon hospital discharge. DESIGN: Electronic cross-sectional survey. SETTING: Academic medical center. PARTICIPANTS: Inpatient physicians and advanced practice providers. MAIN OUTCOME MEASURES: Respondents completed survey items including current naloxone prescribing practices, barriers to naloxone prescribing, and methods to improve naloxone prescribing. RESULTS: The survey response rate was 51.6 percent. Greater than 90 percent of respondents agreed that naloxone should be prescribed for patients with an active opioid use disorder, history of overdose, and use of greater than 50 morphine milligram equivalents per day. Lack of patient education on proper use of naloxone was the most identified barrier to prescribing. CONCLUSIONS: Providers agree with the Centers for Disease Control and Prevention recommendations to prescribe naloxone to high-risk patients. Certain barriers affect the rate of naloxone prescribing at discharge, including lack of time, patient education, provider training, and concern for increasing riskier behaviors.


Assuntos
Overdose de Drogas , Naloxona , Alta do Paciente , Padrões de Prática Médica , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Overdose de Drogas/prevenção & controle , Humanos , Antagonistas de Entorpecentes
3.
J Opioid Manag ; 15(5): 375-387, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849029

RESUMO

OBJECTIVES: Assessment of opioid-induced constipation (OIC) prevalence and relationship with demographic, clinical, and drug predictors in our daily practice. DESIGN: Observational and retrospective study. SETTING: Chronic pain (CP) center of Bologna's Teaching Hospital, Italy. SUBJECTS: Mixed consecutive CP opioid-user outpatients (n = 128). MAIN OUTCOME MEASURE(S): OIC was assessed with the Bowel Function Index (BFI) in three consecutive visits. Absolute difference and Student's t-test were used to compare BFI scores. Predictors (opioid compound and type, morphine-equivalent daily-dose [MEDD], and laxatives) were retrieved from the patients' charts. BFI and predictors relationships were checked by multinomial logistic regression (MLR); independent predictors of BFI scores were assessed with χ2 analysis. RESULTS: Of the 384 evaluations, 85 percent were on strong opioids with a MEDD range of 11-50 mg per day in the majority (60 percent) and 64 percent showed moderate constipation; 42 percent did not use laxatives while 24 percent used macrogol with significant decrease in the BFI. MLR showed that oxycodone was associated with a risk for moderate constipation. Lactulose and glycerin suppositories were associated with severe constipation. Non-opioid users and cancer patients were associated with normal bowel function and severe constipation, respectively. CONCLUSIONS: OIC was found in almost all evaluations of weak or strong opioidusers (97 percent); moderate to severe OIC was found in 72 percent of the evaluations. Cancer patients were associated with severe constipation. Macrogol was superior to other laxatives. In our experience, macrogol relieved constipation in those on the combination of oxycodone and naloxone and in those on fentanyl patches. Lactulose and glycerol suppositories were associated with severe constipation.


Assuntos
Dor Crônica , Constipação Intestinal/induzido quimicamente , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Constipação Intestinal/epidemiologia , Preparações de Ação Retardada , Combinação de Medicamentos , Humanos , Naloxona , Oxicodona , Prevalência , Estudos Retrospectivos
4.
J Opioid Manag ; 15(5): 428-432, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849033

RESUMO

Fentanyl overdoses are growing at an alarming rate. Fentanyl is often mixed into heroin and counterfeit prescription opioid pills without the customer's knowledge and only detected upon laboratory analysis. This is problematic because fentanyl analogues like carfentanil are 10,000 times more potent than morphine and pose new challenges to opioid overdose management. A 62-year-old male with an overdose from a rare fentanyl analogue, acrylfentanyl, was given two doses of intranasal 2 mg naloxone with improvements in respiratory rate. In lieu of more naloxone, his trachea was intubated and he was admitted to the intensive care unit. He subsequently developed ventilator-associated pneumonia and then a pulmonary embolism. He did not receive any opioid use disorder treatment and returned back to the emergency department with an opioid overdose 21 days after discharge. We are encountering an unprecedented rise in synthetic opioid overdose deaths as we enter the third decade of the opioid epidemic. Thus, it is imperative to be aware of the features and management of overdoses from fentanyl and its analogues. This includes protecting against occupational exposure, administering adequate doses of naloxone, and working with public health departments to respond to fentanyl outbreaks. Additionally, fentanyl overdoses represent a critical opportunity to move beyond acute stabilization, start buprenorphine or methadone for opioid use disorder during hospitalization, link patients to ongoing addiction treatment, and distribute naloxone into the community to help curb the overdose epidemic.


Assuntos
Analgésicos Opioides , Overdose de Drogas , Fentanila/envenenamento , Naloxona/administração & dosagem , Analgésicos Opioides/envenenamento , Overdose de Drogas/tratamento farmacológico , Heroína , Humanos , Masculino , Pessoa de Meia-Idade
5.
J Opioid Manag ; 15(6): 479-485, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850509

RESUMO

INTRODUCTION: In response to the US opioid epidemic, the Centers for Disease Control and Prevention issued a guideline (CDCG) for prescribing opioids for chronic pain. Successful implementation of the CDCG requires identification of the information, skills, and support physicians need to carry out its recommendations. However, such data are currently lacking. METHODS: The authors performed one-on-one interviews with nine practicing physicians regarding their needs and perspectives for successful CDCG implementation, including the perceived barriers, focusing on communication strategies. Interviews were audio recorded, transcribed, and a thematic qualitative analysis was performed. FINDINGS: Three major themes were identified: communication, knowledge, and information technology (IT). Physicians reported that open communication with patients about opioids was difficult and burdensome, but essential; they shared their communication strategies. Knowledge gaps included patient-specific topics (eg, availability of/insurance coverage for non-opioid treatments) and more general areas (eg, opioid dosing/equivalencies, prescribing naloxone). Finally, physicians discussed the importance of innovation in IT, focusing on the electronic medical record for decision support and to allow safer opioid prescribing within the time constraints of clinical practice. DISCUSSION: These qualitative data document practical issues that should be considered in the development of implementation plans for safer opioid prescribing practices. Specifically, healthcare systems may need to provide opioid-relevant communication strategies and training, education on key topics such as naloxone prescribing, resources for referrals to appropriate nonpharmacologic treatments, and innovative IT solutions. Future research is needed to establish that such measures will be effective in producing better outcomes for patients on opioids for chronic pain.


Assuntos
Analgésicos Opioides , Comunicação , Registros Eletrônicos de Saúde , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Padrões de Prática Médica , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Tomada de Decisões , Humanos , Naloxona , Médicos , Pesquisa Qualitativa
6.
Tidsskr Nor Laegeforen ; 139(13)2019 Sep 24.
Artigo em Norueguês, Inglês | MEDLINE | ID: mdl-31556537

RESUMO

BACKGROUND: Bystander administration with naloxone nasal spray can prevent deaths from opioid overdose. To achieve optimal nasal absorption of naloxone, the spray must be administered at low volume with high concentration of the drug. The study aimed to investigate the bioavailability and absorption pattern for a new naloxone nasal spray. MATERIAL AND METHOD: In an open, randomised, two-way crossover study undertaken in five healthy men, naloxone 2 mg (20 mg/ml) in nasal spray was compared with 1 mg intravenously administered naloxone. A total of 15 blood samples were taken over a period of six hours after administration. The drug concentration was determined using liquid chromatography tandem-mass spectrometry. Pharmacokinetic variables were calculated using non-compartmental analysis. RESULTS: Bioavailability for intranasal naloxone was 47 % (minimum-maximum values 24-66 %). Maximum concentration (Cmax) was 4.2 (1.5-7.1) ng/ml, and this was achieved (Tmax ) after 16 (5-25) minutes. INTERPRETATION: The nasal spray resulted in a rapid systemic absorption with higher serum concentrations than intravenous naloxone 10-240 minutes after intake. The pilot study indicated that the highly concentrated nasal spray may provide a therapeutic dose of naloxone with a single spray actuation. The findings led to further commercial development of the medication.


Assuntos
Antídotos , Naloxona , Sprays Nasais , Administração Intravenosa , Adulto , Analgésicos Opioides/envenenamento , Antídotos/administração & dosagem , Antídotos/farmacocinética , Disponibilidade Biológica , Estudos Cross-Over , Overdose de Drogas/tratamento farmacológico , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Naloxona/administração & dosagem , Naloxona/farmacocinética , Projetos Piloto , Espectrometria de Massas em Tandem , Adulto Jovem
7.
Toxicol Lett ; 316: 127-135, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539569

RESUMO

Carfentanil (CRF) is an extremely potent opioid capable of inducing fatal respiratory depression. Naloxone (NX) and naltrexone (NTX) are opioid antagonists for which the efficacy against CRF remains largely unexplored. In this study, the effects of aerosolized CRF on respiratory function were investigated using adult male CD-1 mice. Mice were exposed to 0.4 mg/m3 of CRF for 15 min using custom whole-body plethysmograph units. Minute volume (MV), respiratory frequency (f), duty cycle (DC), and tidal volume (TV) were monitored and compared to control animals exposed to aerosolized H2O. CRF exposure induced respiratory depression, characterized by a marked decrease in MV, which was sustained throughout 24 h post-exposure. Prophylactic and therapeutic treatment with intramuscular (i.m.) NX marginally improved MV, with slight dose-dependent effects. Analogous treatment with i.m. NTX returned MV to baseline levels, with all doses and intervention times performing similarly. Despite improvements in MV, treatment administration did not reverse changes in DC, a measure of respiratory timing. Overall, NX and NTX administration alleviated volumetric aspects of opioid-induced respiratory toxicity, while changes in respiratory timing remained unresolved throughout post-exposure observation. These sustained changes and differences in recovery between two aspects of respiratory dynamics may provide insights for further exploration into the underlying mechanism of action of opioids and opioid antagonists.


Assuntos
Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/toxicidade , Fentanila/análogos & derivados , Pulmão/efeitos dos fármacos , Naloxona/administração & dosagem , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Respiração/efeitos dos fármacos , Insuficiência Respiratória/prevenção & controle , Administração por Inalação , Aerossóis , Analgésicos Opioides/farmacocinética , Animais , Simulação por Computador , Relação Dose-Resposta a Droga , Fentanila/administração & dosagem , Fentanila/farmacocinética , Fentanila/toxicidade , Humanos , Pulmão/fisiopatologia , Masculino , Camundongos , Modelos Biológicos , Pletismografia Total , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/fisiopatologia , Medição de Risco
8.
Endocrinology ; 160(11): 2646-2662, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504393

RESUMO

Inflammation elicited by infection or noninfectious insults during gestation induces proinflammatory cytokines that can shift the trajectory of development to alter offspring phenotype, promote adiposity, and increase susceptibility to metabolic disease in later life. In this study, we use mice to investigate the utility of a small molecule Toll-like receptor (TLR)4 antagonist (+)-naloxone, the nonopioid isomer of the opioid receptor antagonist (-)-naloxone, for mitigating altered fetal metabolic programming induced by a modest systemic inflammatory challenge in late gestation. In adult progeny exposed to lipopolysaccharide (LPS) challenge in utero, male but not female offspring exhibited elevated adipose tissue, reduced muscle mass, and elevated plasma leptin at 20 weeks of age. Effects were largely reversed by coadministration of (+)-naloxone following LPS. When given alone without LPS, (+)-naloxone elicited accelerated postweaning growth and elevated muscle and fat mass in adult male but not female offspring. LPS induced expression of inflammatory cytokines Il1a, Il1b, Il6, Tnf, and Il10 in fetal brain, placental, and uterine tissues, and (+)-naloxone suppressed LPS-induced cytokine expression. Fetal sex-specific regulation of cytokine expression was evident, with higher Il1a, Il1b, Il6, and Il10 induced by LPS in tissues associated with male fetuses, and greater suppression by (+)-naloxone of Il6 in females. These data demonstrate that modulating TLR4 signaling with (+)-naloxone provides protection from inflammatory diversion of fetal developmental programming in utero, associated with attenuation of gestational tissue cytokine expression in a fetal sex-specific manner. The results suggest that pharmacologic interventions targeting TLR4 warrant evaluation for attenuating developmental programming effects of fetal exposure to maternal inflammatory mediators.


Assuntos
Desenvolvimento Fetal/efeitos dos fármacos , Naloxona/uso terapêutico , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Receptor 4 Toll-Like/antagonistas & inibidores , Adipocinas/sangue , Animais , Citocinas/sangue , Feminino , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Naloxona/farmacologia , Gravidez , Caracteres Sexuais
9.
BMC Health Serv Res ; 19(1): 632, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488142

RESUMO

BACKGROUND: Overdose deaths can be prevented by distributing take home naloxone (THN) kits. The emergency department (ED) is an opportune setting for overdose prevention, as people who use opioids frequently present for emergency care, and those who have overdosed are at high risk for future overdose death. We evaluated the implementation of an ED-based THN program by measuring the extent to which THN was offered to patients presenting with opioid overdose. We analyzed whether some patients were less likely to be offered THN than others, to identify areas for program improvement. METHODS: We retrospectively reviewed medical records from all ED visits between April 2016 and May 2017 with a primary diagnosis of opioid overdose at a large, urban tertiary hospital located in Alberta, Canada. A wide array of patient data was collected, including demographics, opioid intoxicants, prescription history, overdose severity, and whether a naloxone kit was offered and accepted. Multivariable analyses were used to identify patient characteristics and situational variables associated with being offered THN. RESULTS: Among the 342 ED visits for opioid overdose, THN was offered in 49% (n = 168) of cases. Patients were more likely to be offered THN if they had been found unconscious (Adjusted Odds Ratio 3.70; 95% Confidence Interval [1.63, 8.37]), or if they had smoked or injected an illegal opioid (AOR 6.05 [2.15,17.0] and AOR 3.78 [1.32,10.9], respectively). In contrast, patients were less likely to be offered THN if they had a current prescription for opioids (AOR 0.41 [0.19, 0.88]), if they were admitted to the hospital (AOR 0.46 [0.22,0.97], or if they unexpectedly left the ED without treatment or before completing treatment (AOR 0.16 [0.22, 0.97). CONCLUSIONS: In this real-world evaluation of an ED-based THN program, we observed that only half of patients with opioid overdose were offered THN. ED staff readily identify patients who use illegal opioids or experience a severe overdose as potentially benefitting from THN, but may miss others at high risk for future overdose. We recommend that hospital EDs provide additional guidance to staff to ensure that all eligible patients at risk of overdose have access to THN.


Assuntos
Analgésicos Opioides/envenenamento , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Adulto , Alberta , Overdose de Drogas/reabilitação , Serviços Médicos de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Serviços de Assistência Domiciliar/estatística & dados numéricos , Hospitais Urbanos/estatística & dados numéricos , Humanos , Masculino , Registros Médicos , Transtornos Relacionados ao Uso de Opioides/reabilitação , Estudos Retrospectivos
11.
MMWR Morb Mortal Wkly Rep ; 68(31): 679-686, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31393863

RESUMO

BACKGROUND: The CDC Guideline for Prescribing Opioids for Chronic Pain recommends considering prescribing naloxone when factors that increase risk for overdose are present (e.g., history of overdose or substance use disorder, opioid dosages ≥50 morphine milligram equivalents per day [high-dose], and concurrent use of benzodiazepines). In light of the high numbers of drug overdose deaths involving opioids, 36% of which in 2017 involved prescription opioids, improving access to naloxone is a public health priority. CDC examined trends and characteristics of naloxone dispensing from retail pharmacies at the national and county levels in the United States. METHODS: CDC analyzed 2012-2018 retail pharmacy data from IQVIA, a health care, data science, and technology company, to assess U.S. naloxone dispensing by U.S. Census region, urban/rural status, prescriber specialty, and recipient characteristics, including age group, sex, out-of-pocket costs, and method of payment. Factors associated with naloxone dispensing at the county level also were examined. RESULTS: The number of naloxone prescriptions dispensed from retail pharmacies increased substantially from 2012 to 2018, including a 106% increase from 2017 to 2018 alone. Nationally, in 2018, one naloxone prescription was dispensed for every 69 high-dose opioid prescriptions. Substantial regional variation in naloxone dispensing was found, including a twenty-fivefold variation across counties, with lowest rates in the most rural counties. A wide variation was also noted by prescriber specialty. Compared with naloxone prescriptions paid for with Medicaid and commercial insurance, a larger percentage of prescriptions paid for with Medicare required out-of-pocket costs. CONCLUSION: Despite substantial increases in naloxone dispensing, the rate of naloxone prescriptions dispensed per high-dose opioid prescription remains low, and overall naloxone dispensing varies substantially across the country. Naloxone distribution is an important component of the public health response to the opioid overdose epidemic. Health care providers can prescribe or dispense naloxone when overdose risk factors are present and counsel patients on how to use it. Efforts to improve naloxone access and distribution work most effectively with efforts to improve opioid prescribing, implement other harm-reduction strategies, promote linkage to medications for opioid use disorder treatment, and enhance public health and public safety partnerships.


Assuntos
Naloxona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Farmácias/estatística & dados numéricos , Prescrições/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Overdose de Drogas/mortalidade , Overdose de Drogas/prevenção & controle , Epidemias/prevenção & controle , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
12.
Br J Anaesth ; 123(4): 406-407, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31420087

Assuntos
Naloxona , Humanos
13.
Drugs ; 79(13): 1395-1418, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352603

RESUMO

Naloxone is a well-established essential medicine for the treatment of life-threatening heroin/opioid overdose in emergency medicine. Over two decades, the concept of 'take-home naloxone' has evolved, comprising pre-provision of an emergency supply to laypersons likely to witness an opioid overdose (e.g. peers and family members of people who use opioids as well as non-medical personnel), with the recommendation to administer the naloxone to the overdose victim as interim care while awaiting an ambulance. There is an urgent need for more widespread naloxone access considering the growing problem of opioid overdose deaths, accounting for more than 100,000 deaths worldwide annually. Rises in mortality are particularly sharp in North America, where the ongoing prescription opioid problem is now overlaid with a rapid growth in overdose deaths from heroin and illicit fentanyl. Using opioids alone is dangerous, and the mortality risk is clustered at certain times and contexts, including on prison release and discharge from hospital and residential care. The provision of take-home naloxone has required the introduction of new legislation and new naloxone products. These include pre-filled syringes and auto-injectors and, crucially, new concentrated nasal sprays (four formulations recently approved in different countries) with speed of onset comparable to intramuscular naloxone and relative bioavailability of approximately 40-50%. Choosing the right naloxone dose in the fentanyl era is a matter of ongoing debate, but the safety margin of the approved nasal sprays is superior to improvised nasal kits. New legislation in different countries permits over-the-counter sales or other prescription-free methods of provision. However, access remains uneven with take-home naloxone still not provided in many countries and communities, and with ongoing barriers contributing to implementation inertia. Take-home naloxone is an important component of the response to the global overdose problem, but greater commitment to implementation will be essential, alongside improved affordable products, if a greater impact is to be achieved.


Assuntos
Analgésicos Opioides/efeitos adversos , Overdose de Drogas/tratamento farmacológico , Naloxona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Animais , Medicina de Emergência/métodos , Humanos , Saúde Pública/métodos
14.
J Opioid Manag ; 15(3): 253-259, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31343726

RESUMO

OBJECTIVES: The goal of this study was to investigate whether patients were knowledgeable about naloxone, and whether they would accept overdose (OD) education and naloxone distribution (OEND), if available. DESIGN: This is a cross-sectional study to ascertain participants knowledge about OEND. A questionnaire was designed requesting information regarding age, gender, ethnicity, previous OD experience, type of substance(s) used, availability and use of naloxone for reversal, other treatment interventions utilized if witnessed OD, ways of seeking help for OD, knowledge about OEND, and willingness to accept OEND. SETTING: Study was conducted at the ambulatory detoxification clinic of a tertiary healthcare institution. PARTICIPANTS: Consecutive 131 patients, who presented for primary treatment of opioid detoxification during their visits to the ambulatory detoxification clinic between a predefined timeline from October 2014 through February 2015, were invited to participate, and all 131 agreed to be included in the study. A total of 124 participants returned completed questionnaires (95 percent response rate.) RESULTS: Overall, 68 (52 percent) of the participants indicated that they would accept OEND. A logistic regression analysis showed that younger participants (95% CI: 0.9-1, p = 0.02) and those who identified as non-white (95% CI: 0-0.8, p = 0.01) had higher odds for accepting OEND. Furthermore, prior administration of naloxone was significantly associated with OEND acceptance (95% CI: 1.6-68.6, p = 0.01). CONCLUSIONS: Results indicate more than half of participants presenting for outpatient detoxification from opioids have had an OD or witnessed an OD. More than half of the participants were willing to accept OEND. This study provides evidence that patients starting their recovery are willing to accept naloxone.


Assuntos
Overdose de Drogas , Conhecimentos, Atitudes e Prática em Saúde , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Pacientes Ambulatoriais/psicologia , Analgésicos Opioides , Estudos Transversais , Overdose de Drogas/tratamento farmacológico , Humanos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico
15.
Bull Exp Biol Med ; 167(3): 301-304, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31346864

RESUMO

We studied the possibility of formation of endogenous opioid dependence in rats during periodic intake of 5% ethanol solution. In the control group, both drinking bottles contained water. In the experimental group, the second bottle was filled with 5% ethanol solution for 12 h per day; in the following 12 h, these rats were deprived of food and ethanol. This regimen was maintained over 8 days. The rats were subdivided into alcohol- and water-preferring subgroups. Ethanol deprivation followed by naloxone injection evoked the signs of opiate withdrawal syndrome in both subgroups. These findings suggest that periodic voluntary intake of a weak ethanol solution over 8 days led to the formation of endogenous opioid dependence in rats irrespective of amount of the consumed alcohol.


Assuntos
Etanol/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Animais , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Ratos , Ratos Wistar
16.
Prehosp Disaster Med ; 34(4): 350-355, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31322097

RESUMO

INTRODUCTION: The administration of naloxone therapy is restricted by scope of practice to Advanced Life Support (ALS) in many Emergency Medical Services (EMS) systems throughout the United States. In Delaware's two-tiered EMS system, Basic Life Support (BLS) often arrives on-scene prior to ALS, but BLS providers were not previously authorized to administer naloxone. Through a BLS naloxone pilot study, the researchers sought to evaluate BLS naloxone administration and timing compared to ALS. HYPOTHESIS: After undergoing specialized training, BLS providers would be able to appropriately administer naloxone to opioid overdose patients in a more timely manner than ALS providers. METHODS: This was a retrospective, observational study using data collected from February 2014 through May 2015 throughout a state BLS naloxone pilot program. A total of 14 out of 72 state BLS agencies participated in the study. Pilot BLS agencies attended a training session on the indications and administration of naloxone, and then were authorized to carry and administer naloxone. Researchers then compared vital signs and the time of BLS arrival to administration of naloxone by BLS and ALS. Data were analyzed using paired and independent sample t-tests, as well as chi-square, as appropriate. RESULTS: A total of 131 incidents of naloxone administration were reviewed. Of those, 62 patients received naloxone by BLS (pilot group) and 69 patients received naloxone by ALS (control group). After naloxone administration, BLS patients showed improvements in heart rate (HR; P < .01), respiratory rate (RR; P < .01), and pulse oximetry (spO2; P < .01); ALS patients also showed improvement in RR (P < .01), and in spO2 (P = .005). There was no significant improvement in HR for ALS providers (P = .189).There was a significant difference in arrival time of BLS to the time of naloxone administration between the two groups, with shorter times in the BLS group compared to the ALS group (1.9 minutes versus 9.8 minutes; P < .01); BLS administration was 7.8 minutes faster when compared to ALS administration (95% CI, 6.2-9.3 minutes). CONCLUSIONS: Patients improved similarly and received naloxone therapy sooner when treated by BLS agencies carrying naloxone than those who awaited ALS arrival. All EMS systems should consider allowing BLS to carry and administer naloxone for an effective and potentially faster naloxone administration when treating respiratory compromise related to opiate overdose.


Assuntos
Suporte Vital Cardíaco Avançado/métodos , Reanimação Cardiopulmonar/métodos , Serviços Médicos de Emergência/métodos , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/terapia , Adulto , Idoso , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Naloxona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Segurança do Paciente , Projetos Piloto , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento , Estados Unidos , Adulto Jovem
17.
Health Serv Res ; 54(5): 1055-1064, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31313839

RESUMO

OBJECTIVE: Academic detailing in partnership with the Opioid Overdose Education and Naloxone Distribution (OEND) program was implemented to increase naloxone access for the prevention of opioid overdose mortality in veterans at the U.S. Department of Veterans Affairs (VA). However, implementation was not uniform leading to varying levels of intervention exposure potentially impacting naloxone prescribing. We examined the impact of implementation strength (proportion of providers exposed to academic detailing) at each station on naloxone prescribing from September 2014 to December 2017. STUDY DESIGN AND SETTING: Retrospective cohort design with fixed effects models at the VA. DATA COLLECTION/EXTRACTION METHODS: We used VA Corporate Data Warehouse for data on pharmacy dispensing, station-, provider- and patient-level characteristics. OEND-specific academic detailing activities came from data recorded by academic detailers using Salesforce.com. PRINCIPAL FINDINGS: VA stations wherein 100 percent of providers exposed to an OEND-related academic detailing educational outreach visit experienced an increased incident rate of naloxone prescribing that was 5.52 times the incident rate of stations where no providers were exposed; alternatively, this is equivalent to an average monthly increase of 2.60 naloxone prescriptions per 1000 population at risk for opioid overdose. CONCLUSIONS: Our findings highlight the importance of academic detailing's implementation strength on naloxone prescribing. Decision makers must carefully consider the implementation process to achieve the greatest effectiveness from the intervention.


Assuntos
Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Assistência Farmacêutica/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , United States Department of Veterans Affairs/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos
18.
Pak J Pharm Sci ; 32(3): 911-917, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31278699

RESUMO

Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food manufacturers. Nature has indirectly provided us flavones in our daily diet i.e. tea, fruits, juices and vegetables. Flavones have got special position in research field of natural and synthetic organic chemistry due to their biological capabilities. Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. The structures have been established by different spectroscopic techniques like 1HNMR 13CNMR, IR spectroscopy. The compounds were then screened for their enzyme inhibition potential and antinociceptive response in mice models with writhings induced by acetic acid, tail immersion and formalin-induced nociception assay procedures and structure activity relationship was established. The effects following pretreatment with naloxone were also studied to reveal the involvement of opioid receptors in the antinociceptive action. The flavone derivatives showed moderate to weak inhibition against LOX. Moreover, significant to moderate decrease in the number of abdominal constrictions, increase in paw-licking response time in both phases and a significant raise in latency time in nociception models. Moreover, the antinociceptive response was significantly attenuated by pretreatment with opioid receptor antagonist suggesting the involvement of opioidergic system in the analgesic action. The flavone derivatives showed analgesic response in all models of nociception suggesting the possible involvement of opioidergic system in the antinociceptive action.


Assuntos
Analgésicos/química , Analgésicos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Dor/tratamento farmacológico , Analgésicos/síntese química , Animais , Cristalografia por Raios X , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Flavonoides/síntese química , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Estrutura Molecular , Morfina/farmacologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Dor/etiologia , Espectrofotometria Infravermelho , Testes de Toxicidade Aguda
20.
Am J Health Syst Pharm ; 76(7): 424-435, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-31361827

RESUMO

PURPOSE: The purpose of this review is to (1) provide information concerning the opioid crisis including origins, trends, and some important related laws/policies; and (2) summarize the current involvement and impact of pharmacists in helping to address the crisis, as well as examine practices in other healthcare disciplines from which pharmacists might derive guidance and strategies. SUMMARY: Contributors to the opioid crisis included campaigns to treat pain as a fifth vital sign and to use opioids in treatment of non-cancer-related pain, as well as aggressive marketing of opioid analgesics by pharmaceutical companies. To address the crisis, numerous strategies have been implemented at the policy/legislative, health-system, and patient levels, such as prescription drug monitoring programs (PDMPs), increased regulation of pain clinics, and expanded use of naloxone. Pharmacists have a critical role to play in interventions to address opioid misuse and reduce harm resulting from misuse. Such interventions include patient screening and risk stratification, patient and community education and outreach concerning appropriate pain management, medication reviews/medication therapy management, education on safe storage and disposal, distribution of naloxone/opioid rescue kits and training on their proper use, and referral of patients to addiction treatment, among other strategies. CONCLUSION: Pharmacists have multiple, complex roles in addressing the opioid crisis. Outcomes of several studies provide substantial evidence that pharmacists can make an impact through appropriate pain management, use of PDMPs, opioid overdose prevention training, and medication reviews and counseling, among other interventions.


Assuntos
Analgésicos Opioides/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Manejo da Dor/métodos , Farmacêuticos/organização & administração , Aconselhamento , Publicidade Direta ao Consumidor/legislação & jurisprudência , Revisão de Uso de Medicamentos/organização & administração , Política de Saúde , Humanos , Prescrição Inadequada/efeitos adversos , Prescrição Inadequada/legislação & jurisprudência , Prescrição Inadequada/prevenção & controle , Conduta do Tratamento Medicamentoso/organização & administração , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/etiologia , Transtornos Relacionados ao Uso de Opioides/terapia , Assistência Farmacêutica/organização & administração , Uso Indevido de Medicamentos sob Prescrição/efeitos adversos , Uso Indevido de Medicamentos sob Prescrição/legislação & jurisprudência , Uso Indevido de Medicamentos sob Prescrição/prevenção & controle , Papel Profissional , Estados Unidos/epidemiologia
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