Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.320
Filtrar
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.
Expert Opin Drug Saf ; 19(1): 9-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31868031

RESUMO

Introduction: Reduced drinking has been debated as a treatment goal for heavy drinking alcohol-dependent patients, in whom treatment based on abstinence is not always an option. Nalmefene was the first drug approved by the European Medicines Agency (2013) with the indication of reduced drinking in high drinking risk level alcohol-dependent patients. Six years after its introduction in Europe, data from clinical experience can be compared with those from preclinical studies and pivotal registration studies to evaluate what nalmefene has added to the treatment of AUD.Areas covered: Systematic review of efficacy and safety data of nalmefene use in humans from preclinical, phase III and phase IV studies, including systematic reviews, meta-analyses, cost-effectiveness analyses, and other secondary analyses.Expert opinion: Nalmefene introduces a paradigm change in the treatment of AUD that makes it appealing to patients that are reluctant to embrace abstinence, and facilitate patient-centered care in heavy users. However, information regarding safety data in special populations (e.g., patients with alcohol-related diseases, pregnancy, psychiatric disease), and direct comparisons with other potential drugs for alcohol reduction are further needed. Despite the promising role of nalmefene, there are still some factors that limit its wide prescription further than in specialized settings.


Assuntos
Alcoolismo/tratamento farmacológico , Naltrexona/análogos & derivados , Antagonistas de Entorpecentes/administração & dosagem , Consumo de Bebidas Alcoólicas/prevenção & controle , Transtornos Relacionados ao Uso de Álcool/tratamento farmacológico , Aprovação de Drogas , Humanos , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos
3.
J Opioid Manag ; 15(5): 417-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849032

RESUMO

OBJECTIVE: To evaluate the clinical effects of naltrexone following ALO-02 administration. DESIGN: Two phase three studies: an open-label, single-arm safety study, and a double-blind, placebo-controlled, randomized withdrawal, efficacy study (ClinicalTrials.gov identifiers: NCT01428583, NCT01571362). SETTING: Seventy US research centers. PATIENTS: Eight hundred and five patients with moderate-to-severe chronic noncancer pain (n = 395) or moderate-to-severe chronic low back pain (n = 410). INTERVENTIONS: Oral ALO-02 capsules (daily dose 20-160 mg oxycodone): openlabel titration followed by double-blind fixed dose ALO-02 or placebo (12 weeks) for the efficacy study; and open-label administration (≤12 months) for the safety study. MAIN OUTCOME MEASURES: Brief Pain Inventory-Short Form (BPI-sf), withdrawal-related adverse events, Clinical Opiate Withdrawal Scale (COWS), and naltrexone plasma concentrations. RESULTS: ALO-02 was received for = 30 days by 592 patients (73.5 percent), = 90 days by 348 patients (43.2 percent), and ≤361 days by 105 patients (13.0 percent). Maximum COWS scores were below the cutoff for mild withdrawal for the majority of patients: 86.6 percent of patients in the safety study, and for the efficacy study, 96.8 percent during titration and 95.0 percent during double-blind treatment. The frequency of quantifiable naltrexone plasma concentrations was similar between studies (18-23 percent of samples), and the levels were low, generally not exceeding 200 pg/mL. There was no apparent relationship between naltrexone plasma concentrations and COWS scores (total or change from baseline), or change from baseline in BPI-sf scores in the efficacy (R2 = 0.0184, 0.0224, and 0.0173, respectively) or safety studies (R2 = 0.0010, 0.0000, and 0.0122, respectively). CONCLUSIONS: Naltrexone plasma concentrations were low, not correlated with COWS or BPI-sf scores, and considered clinically insignificant.


Assuntos
Dor Crônica , Naltrexona , Oxicodona , Analgésicos Opioides/administração & dosagem , Dor Crônica/tratamento farmacológico , Preparações de Ação Retardada , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Masculino , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Oxicodona/administração & dosagem , Medição da Dor , Resultado do Tratamento
4.
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
5.
Dermatol Online J ; 25(8)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31553867

RESUMO

Naltrexone is a competitive antagonist of µ, κ and γ opioid receptors, used for treatment of alcoholism and opioid addiction. Low-dose naltrexone (LDN) is defined as daily doses ranging from 1mg to 5mg. This is purported to have a paradoxical effect that leads to an increase in endogenous opioids, including beta-endorphins, which have anti-inflammatory properties. Theses mechanisms may also justify their possible role in the treatment of inflammatory conditions. The aim of this article is to discuss the use of LDN as an adjuvant therapeutic option in symptomatic alopecias presenting with trichodynia. Trichodynia is defined as scalp discomfort of variable intensity presenting as diffuse or localized dysesthesia and may be described by patients as pain, pruritus, or burning. These are common symptoms in patients with hair loss that negatively impacts quality of life. Scalp discomfort may be refractory to conventional therapies and does not yet have a specific therapeutic guideline. For these cases, LDN would be a possible alternative to be added to the therapeutic arsenal owing to its anti-inflammatory properties, analgesic potential, low cost, and few adverse effects described. Further studies are needed to standardize dosing, better understand its mechanism of action, and evaluate its potential therapeutic indications.


Assuntos
Alopecia/tratamento farmacológico , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Dor/tratamento farmacológico , Parestesia/tratamento farmacológico , Prurido/tratamento farmacológico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Humanos
7.
J Consult Clin Psychol ; 87(10): 952-961, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556671

RESUMO

OBJECTIVE: This retrospective study describes the role of behavioral health in an addiction medicine program integrated in a primary care clinic, and evaluates retention, substance use, and mental health symptoms for patients in a rural underserved community. METHOD: Data were abstracted from records of patients referred for buprenorphine treatment of opioid use disorder (N = 101; 45% female, 23% Native Hawaiian or Pacific Islander, Mage = 42.5, SD = 12.75). Among patients prescribed buprenorphine (n = 61), most had comorbid substance-related diagnoses (72% with tobacco use, 75% with at least one other substance use disorder) and non-substance-related mental health diagnoses (77%), most commonly depression and anxiety. Integrated sessions with a behavioral health provider and a buprenorphine-waivered prescriber occurred weekly to monthly. Participants completed depression and anxiety questionnaires (Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7) and provided urine samples at each visit. RESULTS: Most patients (72%) were retained for at least 3 months, with early dropout associated with higher initial depression and anxiety scores. Inconsistent urine drug tests (i.e., those positive for illicit/nonprescribed substances) were significantly more common at treatment initiation (74%) than during the most recent visit (43%, p < .001), and were associated with baseline substance and other mental health factors, as well as shorter treatment duration. Generalized estimating equations models suggested time-based improvements in depression and anxiety symptoms, especially for patients retained for at least 3 months. CONCLUSIONS: Integrating wraparound addiction treatment within a rural primary care setting is feasible and associated with improved mental health and retention outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Medicina do Vício , Buprenorfina/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Atenção Primária à Saúde , Saúde da População Rural , Adulto , Transtornos de Ansiedade/complicações , Buprenorfina/administração & dosagem , Transtorno Depressivo/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/complicações , Estudos Retrospectivos
8.
WMJ ; 118(2): 84-87, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31532934

RESUMO

BACKGROUND: Factors surrounding opioid overdose and naloxone use must be explored from the user perspective in order to more effectively combat the current opioid crisis. METHODS: AIDS Resource Center of Wisconsin needle exchange clients were surveyed regarding overdose victim demographics, interventions, experience with naloxone, and overdose outcomes. RESULTS: Most respondents (102/108, 94.4%) reported either experiencing or witnessing an overdose. While naloxone was often used (64/102, 62.7%), other recommended interventions, such as calling 911 (44/102, 43.1%) and rescue breathing (31/102, 30.4%) often were not. Potential legal consequences were cited as a major barrier for contacting emergency medical services (42.3%). DISCUSSION/CONCLUSION: There appears to be a need for education and/or policy change to facilitate appropriate overdose prevention and use of emergency medical services in the setting of opioid overdose.


Assuntos
Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/prevenção & controle , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Programas de Troca de Agulhas , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Adulto , Serviços Médicos de Emergência , Tratamento de Emergência , Feminino , Humanos , Masculino , Inquéritos e Questionários , Wisconsin
10.
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
11.
Anesthesiology ; 131(2): 381-391, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31314749

RESUMO

BACKGROUND: Although spinal opioids are safe and effective, pruritus is common and distressing. The authors previously demonstrated in mouse spinal cord that interactions between µ-opioid receptor isoform 1D and gastrin releasing peptide receptor mediate morphine-induced scratch. The C-terminal of 1D inhibits morphine-induced scratch without affecting analgesia. The authors hypothesize that human spinal cord also contains itch-specific µ-opioid receptor isoforms which interact with gastrin releasing peptide receptor. METHODS: Reverse transcription polymerase chain reaction was performed on human spinal cord complimentary DNA from two human cadavers. Calcium responses to morphine (1 µM) were examined using calcium imaging microscopy on human cells (HEK293) coexpressing gastrin releasing peptide receptor and different human µ-opioid receptor isoforms. The authors assessed morphine-induced scratching behavior and thermal analgesia in mice following intrathecal injection of morphine (0.3 nmol) and a transactivator of transcription peptide designed from C-terminal sequences of 1Y isoform (0, 0.1, and 0.4 nmol). RESULTS: The authors demonstrated 1Y expression in the spinal cord dorsal horn. Morphine administration evoked a calcium response (mean ± SD) (57 ± 13 nM) in cells coexpressing both gastrin releasing peptide receptor and the 1Y isomer. This was blocked by 10 µM naltrexone (0.7 ± 0.4 nM; P < 0.0001), 1 µM gastrin-releasing peptide receptor antagonist (3 ± 2 nM; P < 0.0001), or 200 µM 1Y-peptide (2 + 2 nM; P < 0.0001). In mice, 0.4 nmol 1Y-peptide significantly attenuated morphine-induced scratching behaviors (scratching bouts, vehicle vs. 1Y-peptide) (92 ± 31 vs. 38 ± 29; P = 0.011; n = 6 to 7 mice per group), without affecting morphine antinociception in warm water tail immersion test (% of maximum possible effect) (70 ± 21 vs. 67 ± 22; P = 0.80; n = 6 mice per group). CONCLUSIONS: Human µ-opioid receptor 1Y isomer is a C-terminal splicing variant of Oprm1 gene identified in human spinal cord. Cross-talk between 1Y and gastrin releasing peptide receptor is required for mediating opioid-induced pruritus. Disrupting the cross talk may have implications for therapeutic uncoupling of desired analgesic effects from side effects of opioids.


Assuntos
Analgésicos Opioides/efeitos adversos , Morfina/efeitos adversos , Prurido/induzido quimicamente , Prurido/prevenção & controle , Receptores da Bombesina/efeitos dos fármacos , Receptores Opioides mu/efeitos dos fármacos , Idoso , Animais , Comportamento Animal , Cadáver , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Medula Espinal
12.
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
14.
Dermatol Online J ; 25(6)2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31329393

RESUMO

Gottron papules, a heliotrope rash, scalp and extremity erythema, pruritus, and fatigue are the characteristic signs and symptoms of amyopathic dermatomyositis (ADM). Amyopathic dermatomyositis is considered a distinct entity from dermatomyositis (DM) because the characteristic muscle weakness and muscle enzyme elevations of DM are absent in ADM. With respects to treatment, ADM treatments have traditionally included topical corticosteroids and/or systemic immunosuppressants and immunomodulators. Herein we present a patient with refractory ADM that was responsive to low-dose naltrexone therapy.


Assuntos
Dermatomiosite/tratamento farmacológico , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico
16.
Expert Rev Clin Pharmacol ; 12(8): 791-803, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31232604

RESUMO

Introduction: Opioid use disorder (OUD) has risen globally and is exerting an enormous toll on public health in many countries, particularly in the United States (US). Buprenorphine (BUP) has become one of the mainstays of pharmacological treatment for OUD and newer delivery methods have been developed to improve its effectiveness in treatment. Areas covered: We provide a review of BUP products available for OUD, with a focus on the newer long-acting formulations. A literature search was conducted using PubMed, Google Scholar, and ClinicalTrials.gov to find randomized clinical trials of long-acting BUP products. Four randomized clinical trials were found: two with BUP implant and two with subcutaneous injectable BUP. Expert opinion: In these clinical trials, new BUP formulations were found to be non-inferior to sublingual (SL) BUP and more effective than placebo in reducing opioid use. Longer-acting formulations can improve flexibility in dosing but superiority over existing SL BUP with regards to outcomes needs to be ascertained. There is a need for more comparative studies between longer-acting BUP formulations and currently available SL BUP. Future studies should also include other clinically meaningful outcomes such as quality of life measures, long-term remission rates, and cost-effectiveness.


Assuntos
Analgésicos Opioides/administração & dosagem , Buprenorfina/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Análise Custo-Benefício , Preparações de Ação Retardada , Humanos , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
AAPS PharmSciTech ; 20(6): 232, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236738

RESUMO

Naloxone is an opioid antagonist with high affinity for µ-opioid receptor, and for this reason it is used for the emergency treatment of opioid overdose. Originally, it was available only as an injectable product. However, for the ease of administration, intranasal (IN) formulations have also become available. These IN formulations contain preservatives and stabilizers such as benzalkonium chloride (BKC), benzyl alcohol (BA), and ethylenediaminetetraacetic acid (EDTA). Some of these ingredients are known to affect permeability of drugs. This study focuses on investigating the effect of formulation variables including choice of preservatives, stabilizer, and pH on the permeability and stability of naloxone IN formulations. The in vitro permeability of naloxone was evaluated employing EpiAirway™ tissue-mounted Ussing chambers. BKC was found to enhance the apparent permeability (Papp) of naloxone significantly (p < 0.05) at very low concentration, while BA caused similar enhancement at a much higher concentration. EDTA was found to decrease Papp of naloxone by lowering the pH, and the Papp of naloxone was found to decrease approximately 51-fold with the decrease in formulation pH from 6.0 to 4.0. The product stability was, however, found optimal only below pH 5.0. Thus, selection of formulation ingredients, buffering agent, and pH of IN formulation is a balancing act for achieving desired permeability and optimal stability to achieve reasonable shelf life of naloxone IN formulation.


Assuntos
Analgésicos Opioides/toxicidade , Overdose de Drogas/prevenção & controle , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Administração Intranasal , Composição de Medicamentos , Ácido Edético/química , Humanos , Concentração de Íons de Hidrogênio , Permeabilidade
20.
JAMA Netw Open ; 2(6): e195388, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31173125

RESUMO

Importance: Despite the increasingly important role of pharmacies in the implementation of naloxone access laws, there is limited information on the impact of such laws at the local level. Objective: To evaluate the availability (with or without a prescription) and cost of naloxone nasal spray at pharmacies in Philadelphia, Pennsylvania, following a statewide standing order enacted in Pennsylvania in August 2015 to allow pharmacies to dispense naloxone without a prescription. Design, Setting, and Participants: A survey study was conducted by telephone of all pharmacies in Philadelphia between February and August 2017. Pharmacies were geocoded and linked with the American Community Survey (2011-2015) to obtain information on the demographic characteristics of census tracts and the Medical Examiner's Office of the Philadelphia Department of Public Health to derive information on the number of opioid overdose deaths per 100 000 people for each planning district. Data were analyzed from March 2018 to February 2019. Main Outcomes and Measures: Availability and out-of-pocket cost of naloxone nasal spray (with or without a prescription) at Philadelphia pharmacies overall and by pharmacy and neighborhood characteristics. Results: Of 454 eligible pharmacies, 418 were surveyed (92.1% response rate). One in 3 pharmacies (34.2%) had naloxone nasal spray in stock; of these, 61.5% indicated it was available without a prescription. There were significant differences in the availability of naloxone by pharmacy type and neighborhood characteristics. Naloxone was both more likely to be in stock (45.9% vs 27.8%; difference, 18.0%; 95% CI, 8.3%-27.8%; P < .001) and available without a prescription (80.6% vs 42.2%; difference, 38.4%; 95% CI, 23.0%-53.8%; P < .001) in chain stores than in independent stores. Naloxone was also less likely to be available in planning districts with very elevated rates of opioid overdose death (≥50 per 100 000 people) compared with those with lower rates (31.1% vs 38.5%). The median (interquartile range) out-of-pocket cost among pharmacies offering naloxone without a prescription was $145 ($119-$150); costs were greatest in independent pharmacies and planning districts with elevated rates of opioid overdose death. Conclusions and Relevance: Despite the implementation of a statewide standing order in Pennsylvania more than 3 years prior to this study, only one-third of Philadelphia pharmacies carried naloxone nasal spray and many also required a physician's prescription. Efforts to strengthen the implementation of naloxone access laws and better ensure naloxone supply at local pharmacies are warranted, especially in localities with the highest rates of overdose death.


Assuntos
Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Farmácias/estatística & dados numéricos , Administração por Inalação , Honorários Farmacêuticos , Gastos em Saúde/estatística & dados numéricos , Humanos , Naloxona/economia , Naloxona/provisão & distribução , Antagonistas de Entorpecentes/economia , Antagonistas de Entorpecentes/provisão & distribução , Sprays Nasais , Medicamentos sem Prescrição/administração & dosagem , Medicamentos sem Prescrição/economia , Medicamentos sem Prescrição/provisão & distribução , Transtornos Relacionados ao Uso de Opioides/economia , Transtornos Relacionados ao Uso de Opioides/reabilitação , Farmácias/economia , Philadelphia , Medicamentos sob Prescrição/administração & dosagem , Medicamentos sob Prescrição/economia , Medicamentos sob Prescrição/provisão & distribução
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA