Clinical Relevance of Linezolid-Associated Serotonin Toxicity (March).
Clinical Relevance of Linezolid-Associated Serotonin Toxicity (March).
Filed under: Drug and Alcohol Rehabilitation
Ann Pharmacother. 2013 Feb 19;
Woytowish MR, Maynor LM
OBJECTIVE:To evaluate and review the literature surrounding serotonin toxicity in patients receiving linezolid and determine the clinical relevance of this reaction.DATA SOURCES:Literature was accessed via MEDLINE/PubMed and Google Scholar (both through February 2013) using the search terms linezolid, serotonin syndrome, serotonin toxicity, and adverse reaction.STUDY SELECTION AND DATA EXTRACTION:Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources.DATA SYNTHESIS:Linezolid exhibits mild, nonselective inhibition of monoamine oxidase and has been associated with serotonin toxicity when used in combination with other serotonergic agents. Based on published reports, the incidence of linezolid-associated serotonin toxicity is between 0.54% and 18.2%. Our review identified 32 documented cases, including 3 fatalities. Most cases occurred in patients concurrently receiving selective serotonin reuptake inhibitors. Receipt of multiple agents with serotonergic activity seems to increase the risk of serotonin toxicity. Both onset and resolution of symptoms varied from hours to days.CONCLUSIONS:Current Food and Drug Administration recommendations to avoid the use of linezolid in patients receiving select serotonergic agents highlight the need to carefully balance the risk/benefit ratio in this situation. Although linezolid has been available for 12 years, reports of serotonin toxicity with this agent are uncommon. While clinicians should be aware of this potentially severe interaction and closely monitor patients who are receiving linezolid in combination with serotonergic agents, our findings show that linezolid is not contraindicated in this situation.
HubMed – drug
Probucol and the cholesterol synthesis inhibitors simvastatin and triparanol regulate Iks channel function differently.
Filed under: Drug and Alcohol Rehabilitation
Hum Exp Toxicol. 2013 Feb 19;
Hihara T, Taniguchi T, Ueda M, Yoshinaga T, Miyamoto N, Sawada K
Channels responsible for slowly activating delayed-rectifier potassium current (I(Ks)) are composed of KCNQ1 and KCNE1 subunits, and these channels play a role in the repolarization of cardiac action potentials. Recently, we showed that the antihyperlipidemic drug probucol, which induces QT prolongation, decreases the I(Ks) after 24-h treatment. In the present study, we investigated the effects of three cholesterol-lowering agents (probucol, an enhancer of cholesterol efflux; simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor; and triparanol, a 3?-hydroxysterol-?24-reductase inhibitor) on cholesterol synthesis, the KCNQ1 current (I(KCNQ1)), and the I(Ks) to clarify the differences in the modes of action of these agents on the I(Ks). Probucol did not inhibit cholesterol synthesis and had no effect on I(KCNQ1), while I(Ks) decreased after 24-h treatment. Simvastatin inhibited cholesterol synthesis and decreased I(KCNQ1) and I(Ks). Additionally, the activation kinetics of I(Ks) became faster, compared with that of control I(Ks). Triparanol inhibited cholesterol synthesis but did not reduce I(KCNQ1) and I(Ks). However, the activation kinetics of I(Ks) became faster. Our data indicated that the mechanism by which probucol inhibits I(Ks) was not mediated by the inhibition of cholesterol synthesis but depended on an interaction with the KCNQ1/KCNE1 complex. Meanwhile, the reduction in cholesterol induced by simvastatin and triparanol is one of the mechanisms that affects the kinetics of I(ks).
HubMed – drug
Enantioselective Iridium-Catalyzed Hydrogenation of 1- and 3-Substituted Isoquinolinium Salts.
Filed under: Drug and Alcohol Rehabilitation
Angew Chem Int Ed Engl. 2013 Feb 19;
Ye ZS, Guo RN, Cai XF, Chen MW, Shi L, Zhou YG
Asymmetric hydrogenation: The title reaction provides an efficient and rapid access to chiral 1- and 3-substituted 1,2,3,4-tetrahydroisoquinolines with excellent enantioselectivity (see scheme; L=ligand). A preliminary mechanistic study indicates that the 1,2-hydride addition might be the initial step in the reaction. The method has been used in the synthesis of urinary antispasmodic drug (+)-solifenacin.
HubMed – drug
Measuring Fidelity and Adaptation: Reliability of a Instrument for School-Based Prevention Programs.
Filed under: Drug and Alcohol Rehabilitation
Eval Health Prof. 2013 Feb 19;
Bishop DC, Pankratz MM, Hansen WB, Albritton J, Albritton L, Strack J
There is a need to standardize methods for assessing fidelity and adaptation. Such standardization would allow program implementation to be examined in a manner that will be useful for understanding the moderating role of fidelity in dissemination research. This article describes a method for collecting data about fidelity of implementation for school-based prevention programs, including measures of adherence, quality of delivery, dosage, participant engagement, and adaptation. We report about the reliability of these methods when applied by four observers who coded video recordings of teachers delivering All Stars, a middle school drug prevention program. Interrater agreement for scaled items was assessed for an instrument designed to evaluate program fidelity. Results indicated sound interrater reliability for items assessing adherence, dosage, quality of teaching, teacher understanding of concepts, and program adaptations. The interrater reliability for items assessing potential program effectiveness, classroom management, achievement of activity objectives, and adaptation valences was improved by dichotomizing the response options for these items. The item that assessed student engagement demonstrated only modest interrater reliability and was not improved through dichotomization. Several coder pairs were discordant on items that overall demonstrated good interrater reliability. Proposed modifications to the coding manual and protocol are discussed.
HubMed – drug
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