Search Results (4)

Background: Opioid dependence treated with buprenorphine/naloxone is associated with increased cardiovascular risk; however, data regarding aortic elasticity and cardiac electrophysiological balance during long-term maintenance therapy remain limited. This study investigated aortic stiffness and distensibility in individuals receiving buprenorphine/naloxone (Suboxone), and examined their associations with echocardiographic and electrocardiographic parameters, including the index of cardiac electrophysiological balance (iCEB and iCEBc). Methods: A retrospective cohort analysis was conducted, including 130 intravenous opioid users receiving Suboxone and 150 age- and sex-matched healthy controls. All participants underwent clinical evaluation, transthoracic echocardiography, resting 12-lead electrocardiography, and 24-h ambulatory blood pressure monitoring. Results: Compared to controls, opioid users demonstrated significantly higher aortic distensibility (median 0.019 vs. 0.015, p < 0.001) and lower aortic stiffness (median 52.31 vs. 64.66, p < 0.001). Patients receiving Suboxone for more than 18 months exhibited higher diastolic blood pressure (p = 0.044), mean arterial pressure (p = 0.046), and pulmonary artery pressure (p = 0.022). Aortic elasticity indices showed strong correlations with blood pressure and echocardiographic parameters. In the overall cohort, Suboxone use duration was not significantly correlated with aortic stiffness or distensibility parameters, while a weak negative correlation was observed with ferritin levels (r = −0.231, p = 0.008). In subgroup analysis of long-term users (>18 months), a moderate positive correlation was observed between therapy duration and iCEB values (r = 0.367, p = 0.001). Conclusions: Chronic buprenorphine/naloxone therapy appears to be associated with changes in aortic elasticity, blood pressure, and mild electrophysiological alterations. These results support the use of non-invasive vascular and electrocardiographic evaluations for cardiovascular risk monitoring and stratification among patients receiving opioid maintenance therapy. Full article

Fetal exposures to many drugs of abuse, e.g., opioids and alcohol (EtOH), are associated with adverse neurodevelopmental problems in early childhood, including abnormalities in activity of the serotonin (5HT) transporter (SERT), which transports 5HT across the placenta. Little is known about the effects of these drugs on SERT expression. Pregnant women who used EtOH or opioids were compared to gestational age-matched controls using a structured questionnaire to determine prenatal substance exposure. Following elective pregnancy termination, placental membranous vesicles and exosomes were prepared from first and second trimester human placentas. Changes in EtOH- or opioid-exposed placental SERT expression and modifications were assessed by quantitative western blot. Novel SERT isoforms were sequenced and analyzed. Opioid-exposed but not EtOH-exposed maternal placentas showed SERT cleavage and formation of new SERT fragments (isoforms). Alcohol-exposed cases showed reduced SERT levels. Antibodies to the N-terminal SERT region did not recognize either of the two cleavage products, while antibodies to the central and C-terminal regions recognized both bands. The secondary band seen in the opioid group may represent a hypophosphorylated SERT fragment. These changes in SERT modifications and expression may result in altered fetal brain serotonergic neurotransmission, which could have neurodevelopmental implications. Full article

Background: Online communities such as Reddit can provide social support for those recovering from opioid use disorder. However, it is unclear whether and how advice-seekers differ from other users. Our research addresses this gap by identifying key characteristics of r/suboxone users that predict advice-seeking behavior. Objective: The objective of this analysis is to identify and describe advice-seekers on Reddit for buprenorphine-naloxone use using text annotation, social network analysis, and statistical modeling techniques. Methods: We collected 5258 posts and their comments from Reddit between 2014 and 2019. Among 202 posts which met our inclusion criteria, we annotated each post to determine which were advice-seeking (n = 137) or not advice-seeking (n = 65). We also annotated each posting user’s buprenorphine-naloxone use status (current versus formerly taking and, if currently taking, whether inducting or tapering versus other stages) and quantified their connectedness using social network analysis. To analyze the relationship between Reddit users’ advice-seeking and their social connectivity and medication use status, we constructed four models which varied in their inclusion of explanatory variables for social connectedness and buprenorphine use status. Results: The stepwise model containing “total degree” (p = 0.002), “using: inducting/tapering” (p < 0.001), and “using: other” (p = 0.01) outperformed all other models. Reddit users with fewer connections and who are currently using buprenorphine-naloxone are more likely to seek advice than those who are well-connected and no longer using the medication, respectively. Importantly, advice-seeking behavior is most accurately predicted using a combination of network characteristics and medication use status, rather than either factor alone. Conclusions: Our findings provide insights for the clinical care of people recovering from opioid use disorder and the nature of online medical advice-seeking overall. Clinicians should be especially attentive (e.g., through frequent follow-up) to patients who are inducting or tapering buprenorphine-naloxone or signal limited social support. Full article

Background: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of evidence-based BUP dosing strategies in this population. Methods: BUP and metabolites concentrations were measured from 0 to 8 h after the administration of sublingual buprenorphine/naloxone films in 12 stable OUD subjects. Results: PK non-compartmental characteristics showed considerable variability in parameters between the subjects over the 8-h sampling time (t_max = 1.5 ± 0.7 h, C_o = 1.6 ± 1.4 ng/mL, C_max= 7.1 ± 6 ng/mL, and AUC_0–8h = 26.8 ± 17.8 h·ng/mL). Subjects had a significantly higher tendency towards CYP-mediated N-demethylation, with the AUC_0–8h ratios of the molar concentrations of [Nor-BUP + Nor-BUP-g] to BUP being (3.4 ± 1.9) significantly higher compared with BUP-g to BUP (0.19 ± 0.2). A two-compartment population-PK model with linear absorption (k_a = 2.54 h⁻¹), distribution (k₁₂= 2.34 h⁻¹, k₁₄ = 1.29 h⁻¹), metabolism (k₂₄ = 1.28 × 10⁻¹ h⁻¹, k₂₃ = 6.43 × 10⁻² h⁻¹, k₃₅ = 1.23 × 10⁻¹ h⁻¹, k₄₅ = 8.73 × 10⁻¹ h⁻¹), and elimination (k₃₀ = 3.81 × 10⁻³ h⁻¹, k₅₀ = 1.27 × 10⁻¹ h⁻¹) adequately described the time-course of BUP and its metabolites, which has been externally validated using published data. Conclusions: Although limited in sampling time and number of recruited subjects, this study presents specific BUP PK characteristics that evidenced the need for additional PK studies and subsequent modeling of the data for the development of evidence-based dosing approaches in Puerto Rico. Full article