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There is no data on the pharmacokinetics of oral transmucosal opioids in patients with salivary gland hypofunction (SGH; 'dry mouth'), despite the fact that SGH may significantly amend absorption through the oral mucosa. Nine cancer patients with pain and SGH (unstimulated whole salivary flow rate<0.1 ml/min) completed a series of pharmacokinetic studies involving a sublingual fentanyl orally disintegrating tablet (Abstral[R]): on the first assessment, plasma fentanyl levels were measured after no intervention for the SGH; on the second assessment, plasma fentanyl levels were measured after moistening the mouth with water; on the third assessment, plasma fentanyl levels were measured after a 5 mg dose of pilocarpine (i.e. salivary stimulant). The Cmax, Tmax, and AUC were lowest during the first assessment phase (i.e. no intervention for SGH). The Cmax, Tmax, and AUC were similar during the second and third assessment phases. Figure 1 shows the plasma concentration–time profiles. The results of this study suggest that moistening the mouth is an effective intervention for improving the pharmacokinetic profile of the sublingual fentanyl orally disintegrating tablet (Abstral[R]) in patients with SGH. However, these results cannot be extrapolated to other oral transmucosal opioids.

Background and aimsMixing opioids and hyperbaric bupivacaine in a single syringe may alter the density of hyperbaric solution, affecting the spread in intrathecal space. To assess the efficacy of premixed versus succedent administration of fentanyl and hyperbaric bupivacaine in subarachnoid block for lower limb surgeries in terms of:Time taken to reach T10 sensory level and modified bromage score 3 for motor block and the duration of sensory and motor blockIncidence of hypotensionPatient and surgeon satisfaction scoreMethods120 patients aged 18–70 years ASA grade I, II and III scheduled for unilateral lower limb surgery were enrolled in this prospective randomized study. Patients were randomly allocated to 3 groups.Group a patients recieved premixed 0.5% hyperbaric bupivacaine 2.5 ml (12.5 mg) and 0.5 ml (25 mcg) of fentanyl in a single 3.0 ml syringeGroup B patients first received 0.5 ml (25 mcg) of fentanyl in a 3.0 ml syringe followed by 0.5% hyperbaric bupivacaine 2.5 ml (12.5 mg) in a 3.0 ml syringeGroup C patients received 0.5% hyperbaric bupivacaine 2.5 ml (12.5 mg) in a 3 ml syringe followed by 0.5 ml (25 mcg) of fentanyl in a 3 ml syringeResultsDifference in mean time to attain T10 sensory level and modified bromage score of 3 was statistically significant among groups a and B (p value <0.05), groups a and C (p value <0.05) and groups B and C (p value <0.05).ConclusionsAdministering hyperbaric bupivacaine first followed by fentanyl (i.e. succedent) leads to an early onset and prolonged duration of sensory and motor block.

Recently, a number of fentanyl analogs have been implicated in overdose deaths in Europe and in the US. So far, little is known of the molecular behavior of the structurally related subgroup; the alicyclic fentanyls. In this study, reference standards of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and 2,2,3,3-tetramethylcyclopropyl fentanyl (TMCPF) at a final concentration of 5 µM were incubated with cryopreserved human hepatocytes (1 × 106 cells/mL) for 0, 1, 3 and 5 h. The metabolites formed were identified by liquid chromatography–quadrupole time-of-flight mass spectrometry analysis. The most abundant biotransformation found was N-dealkylation (formation of normetabolites) and oxidation of the alicyclic rings. As ring size increased, the significance of N-dealkylation decreased in favor of alicyclic ring oxidation. An example of this was cyclopropyl fentanyl, with a three-carbon ring, whose normetabolite covered 82% of the total metabolic peak area and no oxidation of the alicyclic ring was observed. In contrast, TMCPF, with a seven-carbon ring structure, rendered as much as 85% of its metabolites oxidized on the alicyclic ring. Other biotransformations found included oxidation of the piperidine ethyl moiety and/or the phenethyl substructure, glucuronidation as well as amide hydrolysis to form metabolites identical to despropionyl fentanyl. Taken together, this study provides a base for understanding the metabolism of a number of structurally related fentanyl analogs formed upon intake.

Customs and Border Protection increasingly relying on multi-energy portals for scanning freight and private traffic coming from Mexico for fentanyl.

Republican lawmakers heckled and interrupted President Biden multiple times during his State of the Union address on Feb. 7.

Reporter Nick Miroff explains how fentanyl became the most lethal narcotics crisis in U.S. history.

Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

•Data independent screening method for fentanyl analogs in blood and oral fluid.•Limits of detection 0.1–0.25 ng/mL in blood and oral fluid, respectively.•Screening results of authentic blood and oral fluid samples presented. Recently, fentanyl analogs account for significant number of opioid deaths in the United States. Routine forensic analyses are often unable to detect and differentiate these analogs due to low concentrations and presence of structural isomers. A data-independent screening method for 14 fentanyl analogs in whole blood and oral fluid was developed and validated using liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Data were acquired using Time of Flight (TOF) and All Ions Fragmentation (AIF) modes. The limits of detection (LOD) in blood were 0.1–1.0 ng/mL and 0.1–1.0 ng/mL in TOF and AIF modes, respectively. In oral fluid, the LODs were 0.25 ng/mL and 0.25–2.5 ng/mL in TOF and AIF modes, respectively. Matrix effects in blood were acceptable for most analytes (1–14.4%), while the nor-metabolites exhibited ion suppression >25%. Matrix effects in oral fluid were −11.7 to 13.3%. Stability was assessed after 24 h in the autosampler (4 °C) and refrigerator (4 °C). Processed blood and oral fluid samples were considered stable with −14.6 to 4.6% and −10.1 to 2.3% bias, respectively. For refrigerated stability, bias was −23.3 to 8.2% (blood) and −20.1 to 20.0% (oral fluid). Remifentanil exhibited >20% loss in both matrices. For proof of applicability, postmortem blood (n = 30) and oral fluid samples (n = 20) were analyzed. As a result, six fentanyl analogs were detected in the blood samples with furanyl fentanyl and 4-ANPP being the most prevalent. No fentanyl analogs were detected in the oral fluid samples. This study presents a validated screening technique for fentanyl analogs in whole blood and oral fluid using LC-QTOF-MS with low limits of detection.