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1.
J Opioid Manag ; 17(7): 109-118, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34520032

RESUMO

Opioids are an important tool in the treatment of pain, but opioid overdose has become a serious health issue. Most opioid-related deaths are caused by respiratory depression, and the risk of respiratory depression is compounded because of the risks of abuse and diversion, which makes the need for safer opioids even more urgent. However, the atypical opioids (buprenorphine, tramadol, and tapentadol), with mechanisms of action not purely driven by µ-opioid receptor agonism, may be safer than conventional opioids, eg, morphine, oxycodone, and fentanyl. The purpose of this narrative review is to describe the clinical and experimental evidence regarding opioid-induced respiratory depression in the context of the mechanisms of action of the atypical opioids. Among the atypical opioids, tramadol has an advantage of being a Schedule IV drug, and thus having a relatively low abuse potential-but its effects, including its effect on respiratory drive, are dependent on cytochrome P450 2D6 metabolizer status. Tapentadol appears to affect respiratory drive, but this has not been well investigated. Buprenorphine is a Schedule III drug, thus having less abuse potential than the majority of opioids. Experimentally, a ceiling effect on the respiratory depression has been reported with intravenous buprenorphine. In addition, experimental hypercapnic stress in healthy volunteers demonstrated no respiratory depression following the administration of a single dose of the buccal film formulation of buprenorphine when compared with placebo. Overall, the data suggest that atypical opioids may be a safer option than conventional opioids for the treatment of pain.


Assuntos
Analgésicos Opioides , Buprenorfina , Analgésicos Opioides/efeitos adversos , Fentanila , Humanos , Morfina , Oxicodona
2.
Soud Lek ; 66(3): 34-38, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34551557

RESUMO

The article presents the first Polish case of fatal single-substance poisoning with cyclopropylfentanyl, a representative of fentanyl derivatives, whose victim was a 37-year-old man. This opioid was detected in biological material collected during medicolegal autopsy and in the syringe found near the deceased. Blood and urine samples were analyzed using liquid chromatography with mass spectrometry. The concentration of cyclopropylfentanyl was 24 ng/mL in blood and 73 ng/mL in urine.


Assuntos
Analgésicos Opioides , Espectrometria de Massas em Tandem , Adulto , Fentanila/análogos & derivados , Humanos , Masculino , Polônia
3.
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
4.
Artigo em Inglês | MEDLINE | ID: mdl-34444526

RESUMO

Patient-controlled epidural analgesia is widely used to control postoperative pain following major intra-abdominal surgeries. However, determining the optimal infusion dose that can produce effective analgesia while reducing side effects remains a task to be solved. Postoperative pain and adverse effects between variable-rate feedback infusion (VFIM group, n = 36) and conventional fixed-rate basal infusion (CFIM group, n = 36) of fentanyl/ropivacaine-based patient-controlled epidural analgesia were evaluated. In the CFIM group, the basal infusion rate was fixed (5 mL/h), whereas, in the VFIM group, the basal infusion rate was increased by 0.5 mL/h each time a bolus dose was administered and decreased by 0.3 mL/h when a bolus dose was not administered for 2 h. Patients in the VFIM group experienced significantly less pain at one to six hours after surgery than those in the CFIM group. Further, the number of patients who suffered from postoperative nausea was significantly lower in the VFIM group than in the CFIM group until six hours after surgery. The variable-rate feedback infusion mode of patient-controlled epidural analgesia may provide better analgesia accompanied with significantly less nausea in the early postoperative period than the conventional fixed-rate basal infusion mode following open gastrectomy.


Assuntos
Analgesia Epidural , Amidas , Analgésicos Opioides/uso terapêutico , Anestésicos Locais , Retroalimentação , Fentanila , Gastrectomia/efeitos adversos , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , Ropivacaina
5.
J Pak Med Assoc ; 71(8): 1980-1983, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34418014

RESUMO

OBJECTIVE: To compare efficacy of intravenous paracetamol and fentanyl for intra-operative and post-operative analgesia in patients undergoing rigid hysteroscopy. Method: The prospective randomised control trial was conducted at Aga Khan University Hospital, Karachi, from October 2016 to June 2017, and comprised patients aged 18-65 years with American Society of Anesthesiologists grade I or II undergoing hysteroscopy who were randomised into paracetamol group P and fentanyl group F. Anaesthesia induction technique was standardised and analgesia in group P was paracetamol 15mg/Kg administered 15-30 minutes pre-surgery, and in group F, it was fentanyl 2mcg/kg administered at induction of anaesthesia. Intra-operative pain was assessed by changes in heart rate, systolic, diastolic and mean arterial blood pressure, and post-operative pain was assessed using the visual analogue scale. Data was analysed using SPSS 19. RESULTS: Of the 60 patients, there were 30(50%) in each of the two groups. Baseline parameters were similar in the groups except for age differences (p<0.011). In group P, mean systolic blood pressure at 10,15, 20, 25 and 30 minutes, mean diastolic blood pressure at 20, 25 minutes, and mean arterial blood pressure at 20 minutes were statistically significant (p<0.05) compared to group F. The mean heart rate was not significant between the groups (p>0.05). Post-operative pain scores were similar at 0, 15 and 30 minutes (p>0.05). Rescue analgesia was needed in 3(10%) patients in each group on arrival in the recovery room. CONCLUSIONS: Intravenous paracetamol offered analgesic efficacy similar to fentanyl for rigid hysteroscopy in ambulatory surgery.


Assuntos
Acetaminofen , Analgesia , Método Duplo-Cego , Feminino , Fentanila , Humanos , Histeroscopia , Gravidez , Estudos Prospectivos
6.
Molecules ; 26(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34443578

RESUMO

The misuse of fentanyl, and novel synthetic opioids (NSO) in general, has become a public health emergency, especially in the United States. The detection of NSO is often challenged by the limited diagnostic time frame allowed by urine sampling and the wide range of chemically modified analogues, continuously introduced to the recreational drug market. In this study, an untargeted metabolomics approach was developed to obtain a comprehensive "fingerprint" of any anomalous and specific metabolic pattern potentially related to fentanyl exposure. In recent years, in vitro models of drug metabolism have emerged as important tools to overcome the limited access to positive urine samples and uncertainties related to the substances actually taken, the possible combined drug intake, and the ingested dose. In this study, an in vivo experiment was designed by incubating HepG2 cell lines with either fentanyl or common drugs of abuse, creating a cohort of 96 samples. These samples, together with 81 urine samples including negative controls and positive samples obtained from recent users of either fentanyl or "traditional" drugs, were subjected to untargeted analysis using both UHPLC reverse phase and HILIC chromatography combined with QTOF mass spectrometry. Data independent acquisition was performed by SWATH in order to obtain a comprehensive profile of the urinary metabolome. After extensive processing, the resulting datasets were initially subjected to unsupervised exploration by principal component analysis (PCA), yielding clear separation of the fentanyl positive samples with respect to both controls and samples positive to other drugs. The urine datasets were then systematically investigated by supervised classification models based on soft independent modeling by class analogy (SIMCA) algorithms, with the end goal of identifying fentanyl users. A final single-class SIMCA model based on an RP dataset and five PCs yielded 96% sensitivity and 74% specificity. The distinguishable metabolic patterns produced by fentanyl in comparison to other opioids opens up new perspectives in the interpretation of the biological activity of fentanyl.


Assuntos
Fentanila/urina , Toxicologia Forense , Metabolômica , Urinálise/métodos , Cromatografia Líquida , Fentanila/metabolismo , Células Hep G2 , Humanos , Limite de Detecção
7.
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
8.
Molecules ; 26(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361667

RESUMO

Examination of fentanyl levels is frequently performed in certain scientific evaluations and forensic toxicology. It often involves the collection of very variable blood samples, including lipemic plasma or serum. To date, many works have reported the methods for fentanyl detection, but none of them have provided information about the impact on the assay performance caused by an excessive amount of lipids. This aspect may be, however, very important for highly lipophilic drugs like fentanyl. To address this issue, we developed the liquid chromatography method with mass spectrometry detection and utilized it to investigate the impact of lipids presence in rabbit plasma on the analytical method performance and validation. The validation procedure, conducted for normal plasma and lipemic plasma separately, resulted in good selectivity, sensitivity and linearity. The limits of detection and quantification were comparable between the two matrices, being slightly lower in normal plasma (0.005 and 0.015 µg/L) than in lipemic plasma (0.008 and 0.020 µg/L). Liquid-liquid extraction provided a low matrix effect regardless of the lipid levels in the samples (<10%), but pronounced differences were found in the recovery and accuracy. In the normal plasma, this parameter was stable and high (around 100%), but in the lipemic matrix, much more variable and less efficient results were obtained. Nevertheless, this difference had no impact on repeatability and reproducibility. In the present work, we provided reliable, convenient and sensitive method for fentanyl detection in the normal and lipemic rabbit plasma. However, construction of two separate validation curves was necessary to provide adequate results since the liquid-liquid extraction was utilized. Therefore, special attention should be paid during fentanyl quantification that involves lipemic plasma samples purified by this technique.


Assuntos
Analgésicos Opioides/sangue , Fentanila/sangue , Toxicologia Forense/métodos , Hiperlipidemias , Extração Líquido-Líquido/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção , Coelhos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
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
10.
J Environ Manage ; 297: 113327, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311256

RESUMO

The significant increase in illegal use of the synthetic opioid fentanyl is leading to unintentional overdose fatalities. Spills of fentanyl where it is abused or prepared for illegal distribution can result in persistent contamination of areas. Remediation can be attempted through physical removal but may benefit greatly from application of decontamination solutions that provide in-situ degradation of fentanyl. This work investigates the efficacy of decontamination technologies for degradation of fentanyl-HCl on indoor surfaces. Decontamination studies were conducted to evaluate the oxidative degradation of fentanyl based on percarbonate, hydrogen peroxide, peracetic acid, and chlorine (bleach) chemistries. This study utilized an experimental design relevant to field operations to provide direct information to first or hazardous materials responders and providers of environmental fentanyl remediation services, who may otherwise rely on unverified approaches. Across a range of nonporous indoor surfaces, results suggest that water (with or without detergent) spraying alone can physically remove 70-90% of fentanyl (with all fentanyl recovered in runoff). In nearly all cases, the spray application of peracetic acid or acetified bleach oxidants resulted in statistically significant degradation of fentanyl (>95% reduction), with noticeably lower efficacy for other oxidants (e.g., pH neutral bleach and OxiClean™). The decontamination efficacy was significantly reduced upon the addition of cutting agents that competed for oxidant demand.


Assuntos
Descontaminação , Fentanila , Cloro , Peróxido de Hidrogênio , Ácido Peracético
11.
Clin Chim Acta ; 521: 151-154, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34265257

RESUMO

BACKGROUND: Xylazine is an α-2 adrenoreceptor agonist used as a sedative/analgesic in veterinary medicine. Xylazine is known to be present within the street supply of opiates in urban Philadelphia. Medical staff at our hospital asked if we could test for xylazine in fentanyl screen-positive urine samples. We developed an LC-MS/MS assay for this purpose, and determined prevalence of xylazine among fentanyl screen-positive urine samples at our hospital. METHODS: The LC-MS/MS assay utilized d5-norfentanyl as internal standard (IS). One hundred microliter samples were extracted with 200 µl of MeOH/IS. LC was performed using a Phenomenex Kinetix C18 column (100 A, 5 µm, 50 × 4.6 mm) at 40 °C. Time-variable mobile phases (A = H2O, 0.1% formic acid; B = MeOH, 0.1% formic acid) were used at a fixed flow rate of 0.5 ml/min. MS/MS used positive electrospray ionization, monitoring m/z transitions of 221 > 164 for xylazine (primary), 221 > 90 for xylazine (qualifier), and 238 > 84 for d5-norfentanyl (IS). Retention time was 3.9 min for both xylazine and IS. RESULTS: Calibration curve was linear (0-500 ng/ml; r > 0.99). Inter-assay CVs (n = 20) were 5.2% (18 ng/ml) and 6.6% (95 ng/ml). Lower limit of detection was set at 10 ng/ml (CV = 15%). Among 81 urine samples that were screen-positive for fentanyl (Ark Diagnostics immunoassay), 63 (78%) were positive for xylazine (>10 ng/ml). CONCLUSIONS: By LC-MS/MS, there was high prevalence (78%) of xylazine in fentanyl screen-positive urine samples submitted to the laboratory. Because α-2 adrenoreceptor agonists may be used in treatment of opioid addiction, knowledge of xylazine exposure may be clinically useful to guide patient management.


Assuntos
Espectrometria de Massas em Tandem , Xilazina , Cromatografia Líquida , Fentanila , Humanos , Philadelphia , Prevalência , Reprodutibilidade dos Testes
12.
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
13.
Sci Total Environ ; 795: 148838, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34247094

RESUMO

The misuse of fentanyl and more recently tramadol in the population has caused an opioid crisis in several countries and drawn much public attention worldwide. However, there is a gap of information on the potential misuse of fentanyl and tramadol in China. This study aims to fill this gap by analysing fentanyl and tramadol in wastewater of major cities across China to estimate their use. Wastewater samples were collected from 30 cities located across all seven geographic regions of China, from 2016 to 2019. Fentanyl was detected in only a few samples, suggesting a low prevalence of this potent opioid drug in China. Meanwhile, tramadol was found in most samples with concentrations ranging up to 186 ng/L. The per capita daily consumption of tramadol estimated from wastewater across China ranged from 6 mg/d/1000 in. to 213 mg/d/1000 inh. The consumption of tramadol seems to be similar among all the days of the week. Tramadol use is overall higher in Northeast China than in other regions, which is different from heroin, another popular opioid in China. Temporally, there is a significant decrease in tramadol use in major cities of China from 2016 to 2019. The results of our study suggested that tramadol use in China was predominantly from pharmaceutical prescription and not as prevalent as in other countries.


Assuntos
Tramadol , Águas Residuárias , Analgésicos Opioides , China/epidemiologia , Cidades , Fentanila , Águas Residuárias/análise
14.
J Forensic Sci ; 66(5): 1871-1878, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34287912

RESUMO

Oral fluid is a valuable alternative matrix for forensic toxicologists due to ease of observed collection, limited biohazardous exposure, and indications of recent drug use. Limited information is available for fentanyl analog prevalence, interpretation, or analysis in oral fluid. With increasing numbers of fentanyl-related driving under the influence of drug (DUID) cases appearing in the United States, the development of detection methods is critical. The purpose of the present study was to develop and validate a quantitative method for fentanyl analogs in oral fluid (collected via Quantisal™) using liquid chromatography-quadrupole-time-of-flight-mass spectrometry (LC-QTOF-MS). Validation resulted in limits of detection and quantification ranging from 0.5 to 1 ng/mL. Established linear range was 1-100 ng/mL for all analytes, except acetyl fentanyl at 0.5-100 ng/mL (R2  > 0.994). Within- and between-run precision and bias were considered acceptable with maximum values of ±15.2%CV and ±14.1%, respectively. Matrix effects exhibited ionization enhancement for all analytes with intensified enhancement at a low concentration (9.3-47.4%). No interferences or carryover was observed. Fentanyl analogs were stable in processed extracts stored in the autosampler (4° C) for 48h. The validated method was used to quantify fentanyl analogs in authentic oral fluid samples (n=17) from probationers/parolees. Fentanyl and 4-ANPP concentrations were 1.0-104.5 ng/mL and 1.2-5.7 ng/mL, respectively.


Assuntos
Fentanila/análogos & derivados , Fentanila/análise , Saliva/química , Analgésicos Opioides/análise , Cromatografia Líquida , Toxicologia Forense/métodos , Humanos , Espectrometria de Massas/métodos , Detecção do Abuso de Substâncias/métodos
15.
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
16.
Artigo em Inglês | MEDLINE | ID: mdl-34299958

RESUMO

Canada is experiencing an epidemic of opioid-related mortality, with increasing yet heterogeneous fatality patterns from illicit/synthetic (e.g., fentanyl) opioids. The present study examined whether differential provincial reductions in medical opioid dispensing following restrictive regulations (post-2010) were associated with differential contributions of fentanyl to opioid mortality. Annual provincial opioid dispensing totals in defined daily doses/1000 population/day, and change rates in opioid dispensing for the 10 provinces for (1) 2011-2018 and (2) "peak-year" to 2018 were derived from a pan-Canadian pharmacy-based dispensing panel. Provincial contribution rates of fentanyl to opioid-related mortality (2016-2019) were averaged. Correlation values (Pearson's R) between provincial changes in opioid dispensing and the relative fentanyl contributions to mortality were computed for the two scenarios. The correlation between province-based changes in opioid dispensing (2011-2018) and the relative contribution of fentanyl to total opioid deaths (2016-2019) was -0.70 (t = 2.75; df = 8; p = 0.03); the corresponding correlation for opioid dispensing changes ("peak-year" to 2018) was -0.59 (t = -2.06; df = 8; p = 0.07). Provincial reductions in medical opioid dispensing indicated (near-)significant correlations with fentanyl contribution rates to opioid-related death totals. Differential reductions in pharmaceutical opioid availability may have created supply voids for nonmedical use, substituted with synthetic/toxic (e.g., fentanyl) opioids and leading to accelerated opioid mortality. Implications of these possible unintended adverse consequences warrant consideration for public health policy.


Assuntos
Epidemias , Farmácias , Analgésicos Opioides , Canadá/epidemiologia , Fentanila , Humanos
17.
Anal Chem ; 93(29): 10152-10159, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34254788

RESUMO

The reliable identification of fentanyl and its analogs is of great significance for public security. However, with the growing prevalence of fentanyl compounds, current analytical strategies cannot fully meet the need for fast and high-throughput detection. In this study, a simple, rapid, and on-site analytical protocol was developed based on a miniature mass spectrometer. A dramatically simplified workflow was implemented using matrix-assisted ionization, bypassing complex sample pretreatment and chromatographic separation. The tandem mass spectrometry (MS/MS) capability afforded by the miniature ion trap mass spectrometer facilitated the investigation of fragmentation patterns for 49 fentanyl analogs during collision-induced dissociation, revealing valuable information on marker fragment ions and characteristic neutral loss. Calculations on Laplacian bond order values further verified the mass spectrometric behavior. A computation-assisted expandable mass spectral library was constructed in-house for fentanyl compounds. Smart suspect screening was carried out based on the full-scan MS and MS/MS data. The present study demonstrates an appealing potential for forensic applications, enabling streamlined screening for the presence of illicit fentanyl compounds at the point of seizures of suspect samples.


Assuntos
Fentanila , Espectrometria de Massas em Tandem , Medicina Legal , Íons , Espectrometria de Massas por Ionização por Electrospray
18.
Sci Total Environ ; 797: 149109, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34303241

RESUMO

Fentanyls abuse is a persistent international concern. New fentanyl derivatives are constantly appearing, circumventing national and international laws. In this study, laboratory degradation experiment with different conditions such as pH, light, temperature and oxygen availability were compared to improve the understanding of the fentanyls degradation pathways. Twelve major degradants of sufentanil and alfentanil were detected and identified together using UHPLC-QTOF-MS. A total of thirty nine fentanyls including twelve typical fentanyl new psychoactive substances, eighteen manufacturing process-related substances and nine key degradants of sufentanil and alfentanil were screened in 120 sewage water samples collected from 20 sewage water treatment plants chosen among 6 urban cities in east China from July to August in 2020 using a validated UHPLC-MS/MS method. Three fentanyls (fentanyl, sufentanil, alfentanil), seven degradants and six manufacturing process-related substances were found in the test samples. The study could provide a useful tool for the monitoring of the abuses, illegal manufacturing or pharmaceuticals related pollutions of fentanyls and their analogs.


Assuntos
Preparações Farmacêuticas , Esgotos , Cromatografia Líquida , Fentanila , Espectrometria de Massas em Tandem
19.
Brasília; CONITEC; jul. 2021.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1292539

RESUMO

O QUE É DOR CRÔNICA?: A dor crônica é aquela que persiste por um período igual ou superior a três meses. No Brasil, de todas as pessoas que buscam atendimento ambulatorial por causa de dor, entre 28% e 76% se referem a quadros de dor crônica. Essa dor acaba trazendo não apenas sofrimento físico, mas também psicológico, podendo comprometer a qualidade de vida, gerar incapacitação, ansiedade e depressão. COMO OS PACIENTES COM DOR CRÔNICA SÃO TRATADOS NO SUS? O PCDT (Protocolo Clínico e Diretrizes Terapêuticas) da Dor Crônica, publicado em 2012, indica o tratamento farmacológico para os diferentes tipos de dores de acordo com uma escala em degraus numéricos, que correspondem a uma determinada combinação de medicamentos. MEDICAMENTOS ANALISADOS: OPIOIDES FORTES (FENTANILA, OXICODONA E BUPRENORFINA): Os opioides são substâncias químicas que atuam em uma área do cérebro chamada sistema nervoso central e possuem potentes propriedades analgésicas. Os opioides fortes atualmente disponíveis no SUS são a morfina e a metadona. Motivada pela atualização do PCDT da Dor Crônica, a Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde, do Ministério da Saúde (SCTIE/MS), demandou a incorporação dos opioides fortes fentanila, oxicodona e buprenorfina para o tratamento de pacientes com dor crônica no Sistema Único de Saúde (SUS). PERSPECTIVA DO PACIENTE: As chamadas públicas para participar da Perspectiva do Paciente sobre os temas de dor crônica foram abertas em dois períodos distintos: de 13/01/2021 a 17/01/2021 e de 19/01/2021 a 02/02/2021. As quatro chamadas públicas abertas tiveram um total de 32 inscrições. A indicação dos representantes titular e suplente foi feita a partir de consenso entre o grupo de inscritos. RECOMENDAÇÃO INICIAL DA CONITEC: A Conitec recomendou inicialmente a não incorporação dos opioides fortes fentanila, oxicodona e buprenorfina no SUS para o tratamento de dor crônica. Esse tema foi discutido durante a 97ª reunião ordinária da Comissão, realizada nos dias 05 e 06 de maio de 2021. Na ocasião, o Plenário considerou que os resultados das análises não mostraram diferença significante entre os medicamentos mencionados e aqueles disponíveis atualmente no SUS, seja em termos de eficácia ou de segurança. O assunto esteve disponível na consulta pública nº 44, durante 20 dias, no período de 27/05/2021 a 15/06/2021, para receber contribuições da sociedade (opiniões, sugestões e críticas) sobre o tema. RESULTADO DA CONSULTA PÚBLICA: Foram recebidas 65 contribuições, sendo 30 de natureza técnico-científica e 35 de experiência ou opinião. As contribuições abordaram principalmente a necessidade de incorporação dos opióides fortes para dor oncológica. Os resultados da consulta pública, no entanto, não foram suficientes para alterar o entendimento do plenário e a recomendação inicial, desfavorável à incorporação, foi mantida. RECOMENDAÇÃO FINAL DA CONITEC: O Plenário da Conitec, em sua 99ª Reunião Ordinária, no dia 01 de julho de 2021, deliberou por unanimidade recomendar a não incorporação dos opioides fortes (fentanila, oxicodona e buprenorfina) para o tratamento de dor crônica, pois entendeu que as contribuições da consulta pública não trouxeram elementos suficientes para promover a mudança da recomendação preliminar, que ficou mantida. DECISÃO FINAL: Com base na recomendação da Conitec, o secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde, no uso de suas atribuições legais, decidiu pela não incorporação, no âmbito do Sistema Único de Saúde - SUS, dos opioides fortes (fentanila, oxicodona e buprenorfina) para o tratamento de dor crônica.


Assuntos
Humanos , Oxicodona/uso terapêutico , Buprenorfina/uso terapêutico , Fentanila/uso terapêutico , Dor Crônica/tratamento farmacológico , Sistema Único de Saúde , Brasil , Análise Custo-Benefício
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