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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121923, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36183535

RESUMO

The problem of opioid abuse has become a global problem. Thus, creating an urgent need for highly sensitive detection of opioid substances. In this work, we developed a method for the controllable preparation of Ag@Au nanocrystals (Ag@Au NCs) for highly sensitive SERS detection of fentanyl and its analogs. By regulating the concentration of ligands on the surface of silver seed, we successfully prepared Ag@Au NCs with three different morphologies, including core-satellite, yolk shell and hollow structure. Firstly, we explored the SERS-enhancing effect of Ag@Au NCs with different morphology using rhodamine 6G as the molecule to be tested. The results show that the core-satellite Ag@Au NCs has the best SERS effect, and the lowest detection concentration for R6G reached to 10-10 M. Furthermore, we used the prepared core-satellite Ag@Au NCs to detect fentanyl and its five analogs, including carfentanyl, furanylfentanyl, thiofentanyl, 4-fluorobutyrfentanyl and N-4-piperidylacetanilide. Trace detection was achieved for the above six substances. For the environmental water samples spiked with fentanyl, the calculated recovery was 89.2% with an RSD value of 7.3%. Moreover, in order to realize the qualitative analysis of the characteristic peaks of different fentanyl analogs, we performed DFT calculations on the Raman spectra of the above-mentioned 6 substances. By analyzing the DFT calculation results, conventional Raman spectroscopy and SERS spectroscopy, we realized the distinction of six fentanyl analogs with similar structures.


Assuntos
Nanopartículas Metálicas , Análise Espectral Raman , Análise Espectral Raman/métodos , Ouro/química , Nanopartículas Metálicas/química , Prata/química , Fentanila
2.
Forensic Toxicol ; 40(2): 234-243, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36454418

RESUMO

PURPOSE: Since the appearance of fentanyl followed by its many kinds of analogues around 1988, North America has been exposed to fierce synthetic opioid pandemic resulting in more than 130,000 deaths due to their overdoses until May 2019, when China declared to prohibit the licit fentanyl analog production. However, the Chinese announcement did not go into force in USA due to the adroit strategies of tough traffickers. Thus, contrary to the expectation, the number of synthetic opioid products and their poisoning cases in USA has increased by about 30%; especially, various benzimidazole synthetic opioids have revived on the illicit drug market during a recent few years. In this article, the recent abrupt changes in the situations of illicit synthetic opioid market and their current abuses are described. METHODS: Various databases, such as SciFinder, Google, and Google Scholar, were utilized to collect relevant reports referring old but newly appearing synthetic opioids. RESULTS: At the present time, there are several families of new synthetic opioids, which are not fentanyl derivatives; MT-45 and its analogs, benzamide and 2-phenylacetamide opioids (U-series opioids), and benzimidazole opioids. Most of the above substances had been developed in 1950s to 1970s, but had never been used as analgesic medicines, because of their severe adverse effects, such as respiratory depression, physical dependence, and resulting deaths. However, there is possibility that these drugs will become main illicit synthetic opioids in place of the fentanyl analogs during coming several years from this time. CONCLUSIONS: All of the above non-fentanyl-derived families had been developed 50-70 years ago to establish them as analgesic medicines, but had been unsuccessful. These drugs largely appeared in the illicit drug markets in North America, Europe, and Australia, during recent years. Pharmacological, toxicological, and metabolic studies are insufficient for benzamide and 2-phenylacetamide opioids, and are very scant especially for benzimidazole opioids. This time we should start studying pharmacotoxicology of the newly emerging synthetic opioids to alert forensic toxicologists in the world and to suppress their rapid and wide spread in the world.


Assuntos
Benzenoacetamidas , Drogas Ilícitas , Fentanila/efeitos adversos , Analgésicos Opioides/efeitos adversos , Benzamidas , Benzimidazóis
3.
Forensic Toxicol ; 40(1): 199-203, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36454494

RESUMO

PURPOSE: Fentanyl is an analgesic that is frequently prescribed, which resulted in non-intentional as well as intentional misuse and deaths. Here, we present a postmortem case of a patient who clearly died of a fentanyl overdose due to an extensive number of fentanyl patches combined with oral intake of fentanyl and cocaine. We aimed to show how postmortem analysis can be used to interpret postmortem fentanyl concentrations in unique cases like the one we present. CASE DESCRIPTION: A 23-year-old male was found dead in his bedroom with 67 non-prescribed patches of fentanyl on his body. In the room, there also were fentanyl tablets of 100 µg and cocaine powder, which had possibly also been taken by the deceased. To confirm the cause of death, urine and subclavian blood were retrieved to perform a standard postmortem toxicology screening. The toxicological screening revealed the presence of several drugs, including cocaine, fentanyl, lidocaine and paracetamol. Further analysis of the quantitative postmortem values of fentanyl with ultra-performance liquid chromatography-tandem mass spectrometry revealed a fentanyl concentration of 57.9 µg/L. Considering several issues around postmortem drug analyses, this value seemed to be in line with concentrations found in previously reported postmortem cases. CONCLUSION: We were able to confirm the expected cause of death with an extensive toxicological screening in combination with the circumstantial evidence. We identified fentanyl as most important cause for the fatal outcome in this specific case and simultaneously contributed to the limited availability of knowledge on postmortem fentanyl concentrations.


Assuntos
Cocaína , Overdose de Drogas , Overdose de Opiáceos , Masculino , Humanos , Adulto Jovem , Adulto , Fentanila , Overdose de Drogas/diagnóstico , Autopsia
4.
Forensic Toxicol ; 40(1): 156-162, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36454497

RESUMO

PURPOSE: This study aims to expose the toxicity of fentanyl analogs and their metabolites by measuring the agonistic activity of these compounds on opioid receptors. METHODS: The agonistic activity of fentanyl, four analogs of fentanyl (acetylfentanyl, butyrylfentanyl, tetrahydrofuranylfentanyl, and furanylfentanyl), and their metabolites were evaluated using a cell-based assay system, which measured the cellular cAMP level after the reaction of a test compound with cells expressing opioid receptor. RESULTS: Fentanyl and its four analogs showed agonistic activity on µ-opioid receptor at < 10 nM, whereas these compounds were inactive at δ- and κ-opioid receptors even at 100 nM. Similarly, no metabolites showed agonistic activity on δ- and κ-opioid receptors. Meanwhile, several metabolites were active at µ-opioid receptor. ß-Hydroxy metabolites exhibited strong activity nearly equivalent to those of the parent drugs. Some 4'-hydroxy metabolites and N-acyl group-hydroxylated metabolites were still active; however, their activity drastically decreased compared to the parent drugs. CONCLUSIONS: Most of the metabolic reactions drastically diminish the agonistic activity of fentanyl analogs; exceptionally, ß-hydroxylation maintains the activity at a level nearly equal to that of the parent drugs. However, ß-hydroxy metabolites should contribute less to the poisoning caused by the ingestion of fentanyl analogs.


Assuntos
Fentanila , Receptores Opioides , Fentanila/farmacologia , Receptores Opioides kappa , Hidroxilação , Manutenção
5.
Anaesthesiol Intensive Ther ; 54(4): 302-309, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36458667

RESUMO

INTRODUCTION: The benefits of type I/II pectoral nerve blocks (PECS I/II), which can be dose dependent, have been examined in different studies. Nonetheless, few randomised trials have been performed in South America. The present randomised trial examined the efficacy of PECS I/II with a higher dose of the local anaesthetic to manage perioperative pain after mastectomy in Brazil. MATERIAL AND METHODS: This was a randomised, parallel, single-centre, and single-blind trial. Eighty participants undergoing elective mastectomy were randomised (1 : 1) to receive PECS I/II plus ultrasound-guided ropivacaine (0.5%) or standard general anaesthesia. The primary outcome was pain intensity at rest 24 hours after surgery, assessed with a numerical rating scale. Haemodynamic outcomes, consumption of opioids, anaesthe-tics and antiemetics, and post-anaesthetic recovery times were also recorded. RESULTS: Sixty participants (75%) completed the study. The mean age was 54 years, with 57% of participants undergoing mastectomy and 43% undergoing quadrantectomy. Median pain intensity (interquartile range) at rest (24 h postoperatively) was lower in the PECS I/II group compared to the control group: 0 (0-1.75) vs. 1 (1-2), P = 0.021. A smaller number of patients in the PECS I/II group required intraoperative fentanyl (23.3% vs. 83.3%; P < 0.001) and postoperative tramadol (20.0 vs. 76.7%; P < 0.001). Mean doses of fentanyl and tramadol were about 4-5 times lower in the PECS I/II group (P < 0.001). PECS I/II significantly reduced sevoflurane consumption during surgery (P = 0.01). No difference was observed regarding adverse effects. CONCLUSIONS: PECS I/II blockade with high-dose local anaesthetic is efficacious and safe, resulting in lower levels of perioperative pain after mastectomy compared to standard general anaesthesia.


Assuntos
Neoplasias da Mama , Nervos Torácicos , Tramadol , Humanos , Pessoa de Meia-Idade , Feminino , Mastectomia , Anestésicos Locais , Neoplasias da Mama/cirurgia , Estudos Prospectivos , Método Simples-Cego , Fentanila , Dor
6.
Turk J Med Sci ; 52(3): 858-869, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36326322

RESUMO

BACKGROUND: Anesthetics are often used in animal experiments to achieve immobilization and relieve pain. However, many anesthetics can alter the dynamics of cardiovascular systems. We aimed to compare the effects of two frequently used anesthetics agents on heart rate variability (HRV) parameters in mice. METHODS: This observational study was performed between May and June 2014 in 21 male BALB/c mice aged 16-20 weeks. The animals were divided into three groups: pentobarbital (P), (n = 7); pentobarbital+fentanyl (P+F), (n = 7); and ketamine+xylazine (K+X), (n = 7). Surface electrocardiography (ECG) electrodes were placed in lead II configuration. The tachogram of RR intervals was obtained after R waves were detected using the Pan-Tompkins real-time QRS recognition algorithm. Frequency-domain, time-domain, and nonlinear HRV analyses were performed. RESULTS: The bradycardia effect was higher in the K+X group (p < 0.01). Time-domain indices were higher in group K+X compared to group P (p < 0.01) and group P+F (p < 0.001). Very low frequency (VLF) power was significantly lower in group K+X compared to group P and group P+F (p < 0.01). Low frequency (LF) power, low frequency/high frequency (LF/HF) ratio, and total power (TP) were higher in group K+X compared to group P (p < 0.01) and group P+F (p < 0.001). The detrended fluctuation analysis short-term parameter (DFAα1 ) was significantly higher in group K+X compared to group P+F (p < 0.05) and the long-term parameter (DFAα2 ) was lower in group K+X compared to group P (p < 0.05). Standard deviations SD1 and SD2 were higher in group K+X compared to group P (p < 0.001) and group P+F (p < 0.001), SD2/SD1 ratio was lower in group K+X compared to group P (p < 0.05) and group P+F (p < 0.05). Entropy measures did not differ between groups. DISCUSSION: HRV analyses, including nonlinear methods, indicated that a K+X combination reduces imbalance and disorder in the regulation of the autonomic nervous system (ANS) in comparison to both P and the P+F combination.


Assuntos
Anestesia , Anestésicos , Ketamina , Masculino , Camundongos , Animais , Frequência Cardíaca/fisiologia , Xilazina/farmacologia , Ketamina/farmacologia , Pentobarbital/farmacologia , Eletrocardiografia , Fentanila
7.
PLoS One ; 17(11): e0275931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36322521

RESUMO

Electron Impact Gas Chromatography-Mass Spectrometry (EI-GC-MS) and High Resolution Liquid Chromatography-Mass Spectrometry (HR-LC-MS) have been used in the analysis of products arising from the trichloroethoxycarbonylation of fentanyl and acetylfentanyl in urine and plasma matrices. The method involves the initial extraction of both synthetic opioids separately from the matrices followed by detection of the unique products that arise from their reaction with 2,2,2-trichloroethoxycarbonyl chloride (Troc-Cl), namely Troc-norfentanyl and Troc-noracetylfentanyl. The optimized protocol was successfully evaluated for its efficacy at detecting these species formed from fentanyl and acetylfentanyl when present at low and high levels in urine (fentanyl: 5 and 10 ng/mL and acetylfentanyl: 20 and 100 ng/mL) and plasma (fentanyl: 10 and 20 ng/mL and acetylfentanyl: 50 and 200 ng/mL), values that reflect levels reported in overdose victims. The HR-LC-MS method's LOQ (limit of quantitation) for the Troc-norfentanyl and Troc-noracetylfentanyl products was determined to be ~10 ng/mL for both species. Even though the superiority in the detection of these species by HR-LC-MS over EI-GC-MS, the latter method proved to be important in the detection of the second product from the reaction, namely 2-phenylethyl chloride that is crucial in the determination of the original opioid. This observation highlights the importance of using complimentary analytical techniques in the analysis of a sample, whether biological or environmental in nature. The method herein serves as a complementary, qualitative confirmation for the presence of a fentanyl in collected urine, plasma and by extension other biological samples amenable to the common extraction procedures described for opioid analysis. More importantly, the method's main strength comes from its ability to react with unknown fentanyls to yield products that can be not only detected by EI-GC-MS and HR-LC-MS but can then be used to retrospectively identify an unknown fentanyl.


Assuntos
Analgésicos Opioides , Elétrons , Cromatografia Líquida/métodos , Analgésicos Opioides/química , Cromatografia Gasosa-Espectrometria de Massas , Estudos Retrospectivos , Cloretos , Espectrometria de Massas em Tandem/métodos , Fentanila/química
8.
BMC Anesthesiol ; 22(1): 340, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344917

RESUMO

BACKGROUND: Transversus abdominis plane (TAP) block is beneficial for pain management after conducting abdominal surgery. OBJECTIVE: To compare the outcomes of dexmedetomidine and fentanyl, as adjuvants to bupivacaine, for ultrasound-guided TAP block analgesia among patients undergoing radical cystectomy for postoperative pain management. METHODS: This prospective, randomised, comparative study included a total of 60 patients, who underwent radical cystectomy. Participants were randomly divided into three categories with 20 subjects each; group B had patients who received a single shot US-guided TAP block on each side with 20 ml of 0.25% bupivacaine + 2 ml normal saline; group BF had patients who received a single shot US-guided TAP block on each side with 20 ml of 0.25% bupivacaine + 1 µg/kg fentanyl dissolved in 2 ml normal saline and group BD had patients who received a single shot US-guided TAP block on each side with 20 ml of 0.25% bupivacaine + 1 µg/kg dexmedetomidine dissolved in 2 ml normal saline.The researchers recorded the time taken for first rescue analgesia, total analgesic dose in the first 24 h after surgery, patient satisfaction, sedation score, and postoperative complications. RESULTS: The time taken for first rescue analgesia was significantly lengthier in group (BD) (8.90 ± 2.47) than (BF) (6.50 ± 1.43) and (B) (4.40 ± 1.05) groups. The total nalbuphine consumption, during the first 24 h, was significantly lower in (BD) (0.15 ± 0.00) group compared to (BF) (0.20 ± 0.07) and (B) (0.24 ± 0.08) groups. CONCLUSION: In comparison with fentanyl, as an adjuvant to bupivacaine, dexmedetomidine was found to be associated with prolonged postoperative analgesia, less postoperative pain scores and low opioid consumption. TRIAL REGISTRATION: This study was registered at Clinical Trials.gov on 23 March 2020 (registration number: NCT04318158).


Assuntos
Bupivacaína , Dexmedetomidina , Humanos , Fentanila/uso terapêutico , Estudos Prospectivos , Cistectomia , Solução Salina , Anestésicos Locais , Músculos Abdominais/diagnóstico por imagem , Ultrassonografia de Intervenção , Método Duplo-Cego , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico
9.
Harm Reduct J ; 19(1): 129, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36424666

RESUMO

BACKGROUND: While natural disasters like hurricanes are increasingly common, their long-term effects on people who inject drugs are not well understood. Although brief in duration, natural disasters can radically transform risk environments, increasing substance use and drug-related harms. METHODS: Based on a study of people who inject drugs (PWID) and injection risk behaviors in rural Puerto Rico, the present study uses data from two different phases of the parent study. Data for 110 participants were collected from December 2015 to January 2017, soon before Hurricane Maria landed in September 2017; the 2019 phase, in the aftermath of the hurricane, included a total of 103 participants. The present study's main analyses used data from 66 PWID who participated in both the pre-Maria and post-Maria interviews (66 individuals measured at two time points, for a total of 132 observations), using mixed-effects binomial logistic regression to examine recent overdose experiences pre- and post-Maria. A separate descriptive analysis included all 103 participants from the 2019 interview. RESULTS: After Hurricane Maria, some declines in injection frequency were observed (the percentage of people reporting injecting monthly or less increased from 3.0% before Hurricane Maria to 22.7% after Hurricane Maria). However, fewer PWID reported using a new needle for most or all injections. In the pre-Maria interview, 10.6% of participants indicated they had experienced an overdose during the year of the interview and/or the calendar year prior, and this figure increased to 24.2% in the post-Maria interview. In the regression analysis, the odds of reporting an overdose during the interview year and/or calendar year prior were three times as high post-Maria, relative to pre-Maria (odds ratio 3.25, 95% confidence interval 1.06-9.97). CONCLUSION: Substance use patterns, injection risk behaviors, and overdose episodes and deaths differed after Hurricane Maria, relative to before the hurricane, yet it is unclear to what extent these changes also reflect the simultaneous arrival of fentanyl. In preparation for future natural disasters, it is imperative to strengthen the health infrastructure by enhancing access and curbing barriers to syringe services programs and medications for opioid use disorder, particularly in rural or underserved locations.


Assuntos
Tempestades Ciclônicas , Overdose de Drogas , Overdose de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Abuso de Substâncias por Via Intravenosa , Humanos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Assunção de Riscos , Overdose de Drogas/epidemiologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Fentanila
10.
BMC Pregnancy Childbirth ; 22(1): 846, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397024

RESUMO

BACKGROUND: Labour pain has been identified as an important reason for women to prefer caesarean section (CS). Fentanyl is one of the short acting opioids recommended by World Health Organization for pain relief during labour. This study aimed to identify and describe the available evidence on the use of fentanyl (monotherapy) for labour pain management by any routes of administration or regime. METHODS: We included the records published until 31 December 2021 which reported administration of fentanyl to women with normal labour for labour pain relief. Data were extracted by one reviewer and checked by another reviewer using a standardised agreement form. We mapped and presented data descriptively in figure and tabular format. RESULTS: We included 51 records from 49 studies in our scoping review. The studies were conducted in 12 countries, mostly high-income countries. The study designs of the 51 included records were varied as follows: 38 (74.5%) experimental studies (35 randomised controlled trials and three quasi-experimental studies), and 12 (23.5%) observational studies (five retrospective cohort studies, four prospective cohort studies, two retrospective descriptive studies, and one descriptive study) and one qualitative study. Of the included records, six used intranasal fentanyl, five used subcutaneous fentanyl, 18 (35.3%) used intravenous fentanyl, 18 (35.3%) used intrathecal fentanyl, and nine used epidural fentanyl. Many records compared fentanyl with another analgesic agent while five records (9.8%) had no comparison group and seven records (13.7%) compared with no analgesia group. The doses of fentanyl varied by routes, study and the requirement depended on the women. Pain assessment was the most frequent outcome measure presented in the records (78.4%). Only nine records (17.6%) investigated women's satisfaction about labour pain relief using fentanyl and seven records (13.7%) reported the effect of fentanyl on breastfeeding. The most common reported neonatal outcomes were foetal heart rate (33 records, 64.7%) and Apgar score (32 records, 62.7%). CONCLUSION: There is limited primary evidence especially randomised controlled trials to evaluate the effectiveness and harms of different routes of fentanyl in low- or middle-income countries. There is a need for high-quality research to establish the most effective route of fentanyl and associated effects for evidence-based international guidelines.


Assuntos
Dor do Parto , Recém-Nascido , Feminino , Gravidez , Humanos , Dor do Parto/tratamento farmacológico , Fentanila/uso terapêutico , Estudos Retrospectivos , Cesárea , Estudos Prospectivos , Analgésicos/uso terapêutico
11.
Org Lett ; 24(45): 8331-8336, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36346151

RESUMO

An advantageous and original synthesis of fentanyl is described. This new approach includes two efficient continuous flow reductive aminations achieved via photoredox catalysis and a final batch acylation. A telescoped protocol for the two photocatalyzed steps is also presented, and overall, this protocol provides improved sustainability, significant efficiency, reduced temperatures and reaction times, and is functional for scaling up this relevant active pharmaceutical ingredient (API).


Assuntos
Fentanila , Catálise
12.
Int J Mol Sci ; 23(22)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36430883

RESUMO

Three fentanyl analogues Acrylfentanyl, Ocfentanyl and Furanylfentanyl are potent, rapid-acting synthetic analgesics that recently appeared on the illicit market of new psychoactive substances (NPS) under the class of new synthetic opioids (NSO). Pharmacotoxicological data on these three non-pharmaceutical fentanyl analogues are limited and studies on their genotoxicity are not yet available. Therefore, the aim of the present study was to investigate this property. The ability to induce structural and numerical chromosomal aberrations in human lymphoblastoid TK6 cells was evaluated by employing the flow cytometric protocol of the in vitro mammalian cell micronucleus test. Our study demonstrated the non-genotoxicity of Fentanyl, i.e., the pharmaceutical progenitor of the class, while its illicit non-pharmaceutical analogues were found to be genotoxic. In particular, Acrylfentanyl led to a statistically significant increase in the MNi frequency at the highest concentration tested (75 µM), while Ocfentanyl and Furanylfentnyl each did so at both concentrations tested (150, 200 µM and 25, 50 µM, respectively). The study ended by investigating reactive oxygen species (ROS) induction as a possible mechanism linked to the proved genotoxic effect. The results showed a non-statistically significant increase in ROS levels in the cultures treated with all molecules under study. Overall, the proved genotoxicity raises concern about the possibility of serious long-term consequences.


Assuntos
Dano ao DNA , Fentanila , Humanos , Espécies Reativas de Oxigênio , Fentanila/toxicidade
13.
Sci Rep ; 12(1): 18683, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333363

RESUMO

Intravenous lipid emulsions (ILE), among other uses, are utilized in the treatment of poisonings caused by lipophilic substances. The body of evidence regarding the benefits of this treatment is growing but information about opioids-ILE interaction is still very scarce. In this work, the impact of ILE on the distribution of buprenorphine, fentanyl and butorphanol used in various concentrations (100-500 ng/ml) was investigated. Two different in vitro models were used: disposition of the drugs in plasma after ultracentrifugation and distribution into the simulated biophase (cell monolayer of 3T3 fibroblasts or J774.E macrophages). We confirmed the ability of ILE to sequester the three drugs of interest which results in their decrease in the aqueous part of the plasma by 34.2-38.2%, 11.7-28.5% and 6.0-15.5% for buprenorphine, fentanyl and butorphanol, respectively. Moreover, ILE affected the drug distribution to the biophase in vitro, however, in this case the drug concentration in cells decreased by 97.3 ± 3.1%, 28.6 ± 5.4% and 13.0 ± 7.5% for buprenorphine, fentanyl and butorphanol, respectively. The two models revealed notable differences in ILE's potential for drug sequestration, especially for buprenorphine. Similar, but not as pronounced tendencies were observed for the two other drugs. These discrepancies may result from the difference in protein abundance and resulting drug-protein binding in both systems. Nevertheless, the results obtained with both in vitro models correlated well with the partition coefficient (logP) values for these drugs.


Assuntos
Analgésicos Opioides , Buprenorfina , Emulsões Gordurosas Intravenosas/uso terapêutico , Butorfanol , Fentanila
14.
Neurol India ; 70(Supplement): S314-S317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412388

RESUMO

We report the strategy of anesthesia and intraoperative neurophysiological monitoring (IONM) in a 29-year-old, 22 weeks pregnant patient posted for surgery for aggressive vertebral body hemangioma. We used propofol and fentanyl-based anesthesia for IONM. Motor-evoked potentials (MEP) and somatosensory-evoked potentials (SSEP) were used to monitor the neural tracts during surgery. Fetal heart rate monitoring was done preoperatively and postoperatively. Train of 8, 75 µs duration pulse, 250-500 Hz stimulus was used for MEP and 30 mA, 200-400 µs, 3-5 Hz was used for SSEP. No new motor or somatosensory deficits appeared. Our findings suggest that IONM can be safely done in pregnant women.


Assuntos
Potenciais Evocados , Hemangioma , Monitorização Neurofisiológica Intraoperatória , Complicações na Gravidez , Neoplasias da Coluna Vertebral , Adulto , Feminino , Humanos , Gravidez , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Procedimentos Neurocirúrgicos , Estudos Retrospectivos , Coluna Vertebral/cirurgia , Complicações na Gravidez/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Hemangioma/cirurgia , Propofol/administração & dosagem , Fentanila/uso terapêutico , Cardiotocografia , Potenciais Evocados/fisiologia , Anestésicos Intravenosos/uso terapêutico
15.
Lab Chip ; 22(23): 4531-4540, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36331061

RESUMO

Deep learning-enabled smartphone-based image processing has significant advantages in the development of point-of-care diagnostics. Conventionally, most deep-learning applications require task specific large scale expertly annotated datasets. Therefore, these algorithms are oftentimes limited only to applications that have large retrospective datasets available for network development. Here, we report the possibility of utilizing adversarial neural networks to overcome this challenge by expanding the utility of non-specific data for the development of deep learning models. As a clinical model, we report the detection of fentanyl, a small molecular weight drug that is a type of opioid, at the point-of-care using a deep-learning empowered smartphone assay. We used the catalytic property of platinum nanoparticles (PtNPs) in a smartphone-enabled microchip bubbling assay to achieve high analytical sensitivity (detecting fentanyl at concentrations as low as 0.23 ng mL-1 in phosphate buffered saline (PBS), 0.43 ng mL-1 in human serum and 0.64 ng mL-1 in artificial human urine). Image-based inferences were made by our adversarial-based SPyDERMAN network that was developed using a limited dataset of 104 smartphone images of microchips with bubble signals from tests performed with known fentanyl concentrations and using our retrospective library of 17 573 non-specific bubbling-microchip images. The accuracy (± standard error of mean) of the developed system in determining the presence of fentanyl, when using a cutoff concentration of 1 ng mL-1, was 93 ± 0% in human serum (n = 100) and 95.3 ± 1.5% in artificial human urine (n = 100).


Assuntos
Aprendizado Profundo , Nanopartículas Metálicas , Humanos , Fentanila , Estudos Retrospectivos , Platina , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
17.
Cell ; 185(23): 4361-4375.e19, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36368306

RESUMO

Morphine and fentanyl are among the most used opioid drugs that confer analgesia and unwanted side effects through both G protein and arrestin signaling pathways of µ-opioid receptor (µOR). Here, we report structures of the human µOR-G protein complexes bound to morphine and fentanyl, which uncover key differences in how they bind the receptor. We also report structures of µOR bound to TRV130, PZM21, and SR17018, which reveal preferential interactions of these agonists with TM3 side of the ligand-binding pocket rather than TM6/7 side. In contrast, morphine and fentanyl form dual interactions with both TM3 and TM6/7 regions. Mutations at the TM6/7 interface abolish arrestin recruitment of µOR promoted by morphine and fentanyl. Ligands designed to reduce TM6/7 interactions display preferential G protein signaling. Our results provide crucial insights into fentanyl recognition and signaling of µOR, which may facilitate rational design of next-generation analgesics.


Assuntos
Fentanila , Morfina , Humanos , Analgésicos Opioides/farmacologia , Arrestina/metabolismo , Fentanila/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Morfina/farmacologia , Receptores Opioides mu
18.
Mikrochim Acta ; 189(12): 483, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36446842

RESUMO

Fentanyl is a powerful synthetic opioid used to treat severe pain. New administration routes toward its illegal consumption for recreational purposes pose a growing threat to public health, either due to misuse or abuse of this substance. As a result, the rapid qualitative and quantitative determination of fentanyl in biofluids is of great interest. A novel enzymatic biosensor based on adsorptive-stripping cyclic voltammetry is proposed as a cost-effective, reliable, and efficient device for fentanyl determination in urine samples. Disposable screen-printed carbon electrodes modified with multi-walled carbon nanotubes and cytochrome c were used to develop the testing platform. The electrochemical behavior of fentanyl exhibited a well-defined anodic wave around 0.66 V vs. pseudo reference electrode. The experimental conditions were optimized to obtain the best analytical response, and linear regression analysis of increasing concentration standards was applied to estimate the performance parameters. The results suggest a simple method with a wide linearity range, high sensitivity, low limits of detection (0.086 µg/mL) and quantification, and satisfactory precision (2.9% RSD). The feasibility and applicability of the voltammetric approach were assessed by fentanyl-spiked urine samples by standard additions calibration curves in two levels of enrichment with an accuracy of 92% and 100%.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Citocromos c , Fentanila , Eletrodos
19.
Zhonghua Yi Xue Za Zhi ; 102(39): 3121-3126, 2022 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-36274596

RESUMO

Objective: To investigate the impact of the dosage of intraoperative opioids on postoperative survival of pancreatic cancer patients who underwent pancreatectomy. Methods: The clinical data of 95 patients with pancreatic cancer who underwent pancreatectomy at Harbin Medical University Cancer Hospital from September 2013 to August 2018 were retrospectively collected. Dosage of intraoperative opioid medications was converted to fentanyl equivalent dose. Patients were divided into high-dose group (fentanyl consumption ≥2.21 mg, n=46) and low-dose group (fentanyl consumption<2.21 mg, n=49) according to the median intra-operative fentanyl equivalents. The relapse-free survival (RFS) and overall survival (OS) between the two groups were compared. Cox proportional hazards regression model was used to analyze the impact of important covariates on RFS and OS. Results: RFS of patients in low-dose group at 1, 3 and 5 years was 75.5%, 26.5% and 15.2% respectively. OS of patients in low-dose group at 1, 3 and 5 years was 77.6%, 32.5% and 24.4% respectively. RFS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 23.9% and 12.0% respectively. OS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 37.0% and 15.0%. There was no significant difference in RFS and OS between the two groups (all P>0.05). Multivariate Cox analysis showed that dosage of intraoperative fentanyl was not associated with RFS (HR=1.205, 95%CI: 0.737-1.970, P=0.456) or OS (HR=1.062, 95%CI: 0.634-1.778, P=0.818). Conclusion: Dosage of intraoperative opioid has no effect on RFS and OS in pancreatic cancer patients undergoing pancreatectomy.


Assuntos
Analgésicos Opioides , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Fentanila
20.
Trials ; 23(1): 874, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36242089

RESUMO

BACKGROUND: The value of pulsed electromagnetic field (PEMF) in postoperative pain management, due to the inconsistent findings so far, remains unclear. We extended the evaluation of PEMF on postoperative pain and intravenous (IV) analgesic use to a group of post-appendicectomy Asian patients. METHODS: This is a double-blinded, randomized trial. Adults with a clinical diagnosis of acute appendicitis were enrolled. Patients were allocated randomly to receive an active-PEMF device or an inactive device after the surgery in addition to the standard postoperative pain management. The primary outcome measure was the 12-h cumulative postoperative pain intensity measured at four different time points using the visual analogue scale. The secondary outcome measure was the total amount of IV fentanyl used (in mg) via PCA over the first 12 postoperative hours. The primary analysis in this trial compared the two study groups for the reported cumulative pain score (both at rest and on movement) and the cumulative amount of IV fentanyl uses over the first 12 postoperative hours using the Wilcoxon rank sum test. Analyses were performed based on the intention-to-treat principal. Multiple imputation was used to handle the missing data assuming that the data were missing at random. FINDINGS: One hundred eighteen subjects were randomized; 58 were allocated to the active-PEMF group and 60 to the inactive control group. Pooled mean pain score of both intervention groups by time point declined in a similar fashion over the course of 12 postoperative hours. The 12-h cumulative postoperative pain score at rest and on movement did not differ significantly after the procedure. (W = 1832.5 ~ 1933.0, p-value 0.6192 ~ 0.2985 for resting pain score comparison; W = 1737.0 ~ 1804.5, p-value 0.9892 ~ 0.7296 for movement pain score comparison). For the secondary outcome measure of 12-h total fentanyl use, a comparison between the PEMF vs. placebo arm also revealed no statistically significant difference across all the 20 imputed datasets (W = 1676.5 ~ 1859.0, p-value 0.7344 ~ 0.5234). DISCUSSION: PEMF was not superior to placebo as an adjunct pain management for up to 12 h post-appendicectomy. Previously reported effect of PEMF on postoperative pain intensity and analgesia uses in similar surgical settings cannot be verified. TRIAL REGISTRATION: National Medical Research Register Malaysia (NMRR-15-670-25,805) and Thai Clinical Trials Registry (retrospectively registered on November 01, 2019, Study ID-TCTR20191102002).


Assuntos
Campos Eletromagnéticos , Dor Pós-Operatória , Adulto , Analgésicos/uso terapêutico , Fentanila/efeitos adversos , Humanos , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle
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