Could pharmacogenetic data explain part of the interindividual sensitivity to methadone-induced respiratory depression?

In this issue of Critical Care, Megarbane and colleagues present a case report of methadone-induced respiratory depression and conduct a toxicokinetic/toxicodynamic evaluation. An opioid-dependent patient receiving methadone maintenance treatment (daily dose 70 mg) was found unconscious after ingesting 240 mg methadone and 2 mg flunitrazepam. Significant improvement in consciousness was achieved after an intravenous bolus of 0.3 mg naloxone followed by a continuous infusion of naloxone at 0.3 mg/hour. In patients receiving methadone maintenance treatment, an occasional intake of two to four times the usual daily dose of methadone is not an exceptional occurrence. However, few such patients experience episodes of life-threatening respiratory depression. Here, we discuss whether recent pharmacogenetic data could help us to understand interindividual variability in sensitivity to respiratory depression and, ultimately, to predict which patients are most likely to be affected

Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study

Purpose: To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics. Methods: Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose. Results: Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14-16% and 17-25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4. Conclusion: Cannabis use and higher methadone doses in MMT could in part be a response to—or a cause of—more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MM

Case Report Addition of Aripiprazole to the Clozapine May Be Useful in Reducing Anxiety in Treatment-Resistant Schizophrenia

There exist many case reports and studies on the antipsychotic augmentation by aripirazole in partial responders to clozapine, the most seem to be finding a slight difference in the PANSS and CGI scores after the aripirazole addition. The results of our report are compatible with those of other studies but, we have found a considerable antianxiety action in both of the cases. The 5HT1A agonism of aripirazole could be hypothesized as mechanism contributing to this effect

Olanzapine‐associated dose‐dependent alterations for weight and metabolic parameters in a prospective cohort

Metabolic abnormalities have been associated with olanzapine treatment. We assessed if olanzapine has dose-dependent effects on metabolic parameters with changes for weight, blood pressure, lipid and glucose profiles being modelled using linear mixed-effects models. The risk of metabolic abnormalities including early weight gain (EWG) (≥5% during first month) was assessed using mixed-effects logistic regression models. In 392 olanzapine-treated patients (median age 38.0 years, interquartile range [IQR] = 26.0-53.3, median dose 10.0 mg/day, IQR = 5.0-10.0 for a median follow-up duration of 40.0 days, IQR = 20.7-112.2), weight gain was not associated with olanzapine dose (p = 0.61) although it was larger for doses versus ≤10 mg/day (2.54 ± 5.55 vs. 1.61 ± 4.51% respectively, p = 0.01). Treatment duration and co-prescription of >2 antipsychotics, antidepressants, benzodiazepines and/or antihypertensive agents were associated with larger weight gain (p 10 mg/day were at higher EWG risk (odds risk: 2.15, 1.57-2.97). EWG might be prominent in high-dose olanzapine-treated patients with treatment duration and co-prescription of other medications being weight gain moderators. The lack of major dose-dependent patterns for weight gain emphasizes that olanzapine-treated patients are at weight gain risk regardless of the dose

Arbeitsmedizin

Das Kapitel ist in vier Unterkapital gegliedert. "Allgemeines zur Arbeitsmedizin" beinhaltet die Rolle und Ziele der Arbeitsmedizin und die wesentlichen gesetzlichen Grundlagen. "Berufskrankheiten" umfasst die Berufs- und Arbeitsplatzanamnese sowie die wichtigsten Berufskrankheiten und Noxen. Das dritte Unterkapitel behandelt die arbeitsassoziierten Gesundheitsstörungen, die Ergonomie, Arbeitsorganisation und Arbeitslosigkeit. Die Kapitel "Absenzen- und Case Management" sowie "Betriebliche Gesundheitsförderung und Arbeitsgestaltung" zeigen Möglichkeiten auf, wie ein Betrieb die Gesundheit und Arbeitsfähigkeit seiner Mitarbeiter aufrechterhalten und fördern kann. Das Kapitel befähigt die Studierenden, die Interaktion zwischen Arbeit und Gesundheit zu erkennen und adäquate Massnahmen zu ergreifen.[Autoren]]]> Occupational Medicine ; Occupational Diseases oai:serval.unil.ch:BIB_EFD9005BC107 2020-05-30T01:25:30Z phdthesis urnserval https://serval.unil.ch/notice/serval:BIB_EFD9005BC107 Résultats à court terme des arthroplasties totales de hanche non cimentées chez des patients de moins de 60 ans Larequi, Ivan-Philippe Université de Lausanne, Faculté de médecine info:eu-repo/semantics/doctoralThesis phdthesis 1999 fre https://serval.unil.ch/resource/serval:BIB_EFD9005BC107.P001/REF.pdf http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_EFD9005BC1073 info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_EFD9005BC1073 info:eu-repo/semantics/restrictedAccess Restricted: indefinite embargo Copying allowed only for non-profit organizations https://serval.unil.ch/disclaimer application/pdf oai:serval.unil.ch:BIB_EFD90D5BB70B 2020-05-30T01:25:30Z openaire documents urnserval https://serval.unil.ch/notice/serval:BIB_EFD90D5BB70B Association Between Plasma Caffeine and Other Methylxanthines and Metabolic Parameters in a Psychiatric Population Treated With Psychotropic Drugs Inducing Metabolic Disturbances info:doi:10.3389/fpsyt.2018.00573 info:eu-repo/semantics/altIdentifier/doi/10.3389/fpsyt.2018.00573 info:eu-repo/semantics/altIdentifier/pmid/30473668 Delacrétaz, Aurélie Vandenberghe, Frederik Glatard, Anaïs Levier, Axel Dubath, Céline Ansermot, Nicolas Crettol, Séverine Gholam-Rezaee, Mehdi Guessous, Idris Bochud, Murielle von Gunten, Armin Conus, Philippe Eap, Chin B. info:eu-repo/semantics/article article 2018-11-09 Frontiers in Psychiatry, vol. 9 info:eu-repo/semantics/altIdentifier/pissn/1664-0640 <![CDATA[Importance: Multiple studies conducted in the general population identified an association between self-reported coffee consumption and plasma lipid levels. To date, no study assessed whether and which plasma methylxanthines (caffeine and/or its metabolites, i.e., paraxanthine, theophylline, and theobromine) are associated with plasma lipids. In psychiatric patients, an important coffee consumption is often reported and many psychotropic drugs can induce a rapid and substantial increase of plasma lipid levels. Objective: To determine whether plasma methylxanthines are associated with metabolic parameters in psychiatric patients receiving treatments known to induce metabolic disturbances. Design, Setting, and Participants: Data were obtained from a prospective study including 630 patients with metabolic parameters [i.e., body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and fasting triglycerides (TG)] monitored routinely during psychotropic treatment. Exposures: Plasma methylxanthines levels. Main Outcomes and Measures: Metabolic variables including BMI and plasma lipid levels. Results: Multivariate analyses indicated that BMI, TC, HDL-C, and non-HDL-C increased significantly with increasing total methylxanthines (pcorrected &lt;= 0.05). In addition, compared to patients with plasma caffeine concentration in the lowest quartile, those with caffeine concentration in the highest quartile were twice more prone to suffer from non-HDL hypercholesterolemia (p(corrected) = 0.05), five times more likely to suffer from hypertriglyceridemia (p(corrected) = 0.01) and four times more susceptible to be overweight (p(corrected) = 0.01). Conclusions and Relevance: This study showed that plasma caffeine and other methylxanthines are associated with worsening of metabolic parameters in patients receiving psychotropic treatments known to induce metabolic disturbances. It emphasizes that important caffeine consumption could be considered as an additional environmental risk factor for metabolic worsening in patients receiving such treatments

Association Between Plasma Caffeine and Other Methylxanthines and Metabolic Parameters in a Psychiatric Population Treated With Psychotropic Drugs Inducing Metabolic Disturbances

Importance: Multiple studies conducted in the general population identified an association between self-reported coffee consumption and plasma lipid levels. To date, no study assessed whether and which plasma methylxanthines (caffeine and/or its metabolites, i.e., paraxanthine, theophylline, and theobromine) are associated with plasma lipids. In psychiatric patients, an important coffee consumption is often reported and many psychotropic drugs can induce a rapid and substantial increase of plasma lipid levels.Objective: To determine whether plasma methylxanthines are associated with metabolic parameters in psychiatric patients receiving treatments known to induce metabolic disturbances.Design, Setting, and Participants: Data were obtained from a prospective study including 630 patients with metabolic parameters [i.e., body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and fasting triglycerides (TG)] monitored routinely during psychotropic treatment.Exposures: Plasma methylxanthines levels.Main Outcomes and Measures: Metabolic variables including BMI and plasma lipid levels.Results: Multivariate analyses indicated that BMI, TC, HDL-C, and non-HDL-C increased significantly with increasing total methylxanthines (pcorrected ≤ 0.05). In addition, compared to patients with plasma caffeine concentration in the lowest quartile, those with caffeine concentration in the highest quartile were twice more prone to suffer from non-HDL hypercholesterolemia (pcorrected = 0.05), five times more likely to suffer from hypertriglyceridemia (pcorrected = 0.01) and four times more susceptible to be overweight (pcorrected = 0.01).Conclusions and Relevance: This study showed that plasma caffeine and other methylxanthines are associated with worsening of metabolic parameters in patients receiving psychotropic treatments known to induce metabolic disturbances. It emphasizes that important caffeine consumption could be considered as an additional environmental risk factor for metabolic worsening in patients receiving such treatments

Services sociaux en Valais: des réponses différenciées pour affronter les nouveaux enjeux professionnels

« Je suis assistante sociale » ; à l’énoncé de cette affirmation, les avis divergent significativement. Si certains sont admiratifs, d’autres plutôt méfiants. Les assistantes sociales doivent trouver leur place dans cette ambivalence, qui n’est d’ailleurs pas la seule au sein du travail social. Comment les assistantes sociales construisent-elles leur identité professionnelle ? Comment se situent-elles dans une profession si controversée ? En s’appuyant sur plusieurs entretiens effectués avec des assistantes sociales de différents milieux, tout en développant les grandes mutations du travail social durant la dernière décennie, ce travail a pour but d’identifier les moteurs qui poussent les assistantes sociales à effectuer ce métier de l’humain. Il dresse un éventail de leurs motivations, de leurs perceptions tout en s’arrêtant particulièrement sur leurs découragements afin de révéler les stratégies et ressources mises en place pour ne pas céder au poids du contrôle et de l’administratif grandissant. Au terme de ce document, quelques pistes sont abordées afin d’accompagner le lecteur dans une réflexion globale, spécifiquement autour de la reconnaissance de l’intervention sociale au sein de la société

Pharmacogenetic studies on methadone and immunosuppressive drugs

La méthadone est un agoniste du récepteur mu aux opiacés utilisé comme traitement de substitution lors de la dépendance aux opiacés. Ce travail a pemis de démontrer que les cytochromes P450 (CYP) 3A4 et CYP2B6 sont les principaux CYPs impliqués dans le métabolisme de la méthadone. Le CYP2B6 présente une stéréosélectivité vis-à-vis de la (S)-méthadone, inactive sur le récepteur mu mais qui inhibe plus fortement le canal cardiaque hERG. Les polymorphismes génétiques de la P-glycoprotéine contribuent légèrement à la variabilité de la pharmacocinétique de la méthadone. Toutefois, les polymorphismes de ces quatres protéines n'influencent pas la réponse thérapeutique au traitement alors que les métaboliseurs lents du CYP2B6 sont associés à un risque supérieur de cardiotoxicité. La ciclosporine est un immunosuppresseur prescrit pour prévenir les rejets de greffe suite à une transplantation. Les polymorphismes génétiques de la P-glycoprotéine influencent ses concentrations intracellulaires et pourraient donc influencer la réponse au traitement immunosuppresseur

Pharmacokinetic and pharmacogenetic factors influencing methadone plasma levels

Methadone is widely used as a maintenance treatment for opiate addiction. Methadone plasma levels vary widely for a given dose, so contributing to interindividual variability in response to methadone maintenance treatment. Until recently, the relative in vivo involvement of various cytochrome P450 (CYP) isoforms in methadone pharmacokinetics had been unclear. A recent large-scale pharmacogenetic study with patients in methadone maintenance treatment has now demonstrated that CYP3A4 and CYP2B6 are the major cytochrome P450 isoforms with a major involvement in methadone metabolism, while CYP2D6 only contributes to a minor extent. In addition, P-glycoprotein, a transmembrane efflux protein, is also involved in methadone kinetics