Comprehensive Screening of Diuretics in Human Urine Using Liquid Chromatography Tandem Mass Spectrometry
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In Silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction
In silico Methods for Drug Repositioning and Drug-Drug Interaction Prediction Pathima Nusrath Hameed ORCID: 0000-0002-8118-9823 Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy Department of Mechanical Engineering THE UNIVERSITY OF MELBOURNE May 2018 Copyright © 2018 Pathima Nusrath Hameed All rights reserved. No part of the publication may be reproduced in any form by print, photoprint, microfilm or any other means without written permission from the author. Abstract Drug repositioning and drug-drug interaction (DDI) prediction are two fundamental ap- plications having a large impact on drug development and clinical care. Drug reposi- tioning aims to identify new uses for existing drugs. Moreover, understanding harmful DDIs is essential to enhance the effects of clinical care. Exploring both therapeutic uses and adverse effects of drugs or a pair of drugs have significant benefits in pharmacology. The use of computational methods to support drug repositioning and DDI prediction en- able improvements in the speed of drug development compared to in vivo and in vitro methods. This thesis investigates the consequences of employing a representative training sam- ple in achieving better performance for DDI classification. The Positive-Unlabeled Learn- ing method introduced in this thesis aims to employ representative positives as well as reliable negatives to train the binary classifier for inferring potential DDIs. Moreover, it explores the importance of a finer-grained similarity metric to represent the pairwise drug similarities. Drug repositioning can be approached by new indication detection. In this study, Anatomical Therapeutic Chemical (ATC) classification is used as the primary source to determine the indications/therapeutic uses of drugs for drug repositioning. -
Use of ²-Blockers and Risk of Fractures
ORIGINAL CONTRIBUTION Use of -Blockers and Risk of Fractures Raymond G. Schlienger, PhD, MPH Context Animal studies suggest that the -blocker propranolol increases bone for- Marius E. Kraenzlin, MD mation, but data on whether use of -blockers (with or without concomitant use of thiazide diuretics) is associated with reduced fracture risk in humans are limited. Susan S. Jick, DSc Objective To determine whether use of -blockers alone or in combination with thia- Christoph R. Meier, PhD, MSc zides is associated with a decreased risk of fracture in adults. Design, Setting, and Participants Case-control analysis using the UK General Prac- TUDIES HAVE SUGGESTED THAT tice Research Database (GPRD). The study included 30601 case patients aged 30 to the sympathetic nervous sys- 79 years with an incident fracture diagnosis between 1993 and 1999 and 120819 con- tem has a catabolic effect on trols, matched to cases on age, sex, calendar time, and general practice attended. bones.1-4 In vitro data show that Main Outcome Measures Odds ratios (ORs) of having a fracture in association Sadrenergic agonists stimulate bone re- with use of -blockers or a combination of -blockers with thiazides. sorption in organ culture of mouse cal- Results The most frequent fractures were of the hand/lower arm (n=12837 [42.0%]) variae.4 Chemical sympathectomy with and of the foot (n=4627 [15.1%]). Compared with patients who did not use either guanethidine, a sympathetic neuro- -blockers or thiazide diuretics, the OR for current use of -blockers only (Ն3 pre- toxic agent, impairs bone resorption by scriptions) was 0.77 (95% confidence interval [CI], 0.72-0.83); for current use of thia- inhibiting preosteoclast differentiation zides only (Ն3 prescriptions), 0.80 (95% CI, 0.74-0.86); and for combined current  and disturbing osteoclast activation in use of -blockers and thiazides, 0.71 (95% CI, 0.64-0.79). -
Health Reports for Mutual Recognition of Medical Prescriptions: State of Play
The information and views set out in this report are those of the author(s) and do not necessarily reflect the official opinion of the European Union. Neither the European Union institutions and bodies nor any person acting on their behalf may be held responsible for the use which may be made of the information contained therein. Executive Agency for Health and Consumers Health Reports for Mutual Recognition of Medical Prescriptions: State of Play 24 January 2012 Final Report Health Reports for Mutual Recognition of Medical Prescriptions: State of Play Acknowledgements Matrix Insight Ltd would like to thank everyone who has contributed to this research. We are especially grateful to the following institutions for their support throughout the study: the Pharmaceutical Group of the European Union (PGEU) including their national member associations in Denmark, France, Germany, Greece, the Netherlands, Poland and the United Kingdom; the European Medical Association (EMANET); the Observatoire Social Européen (OSE); and The Netherlands Institute for Health Service Research (NIVEL). For questions about the report, please contact Dr Gabriele Birnberg ([email protected] ). Matrix Insight | 24 January 2012 2 Health Reports for Mutual Recognition of Medical Prescriptions: State of Play Executive Summary This study has been carried out in the context of Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the application of patients’ rights in cross- border healthcare (CBHC). The CBHC Directive stipulates that the European Commission shall adopt measures to facilitate the recognition of prescriptions issued in another Member State (Article 11). At the time of submission of this report, the European Commission was preparing an impact assessment with regards to these measures, designed to help implement Article 11. -
New Prohibited Substances Addition to Procedures Using Triple Quadrupole LC/MS2 Technique
Poster MANFRED DONIKE WORKSHOP Pop V, Bican G, Pop A, Lamor M, Zorio M New prohibited substances addition to procedures using triple quadrupole LC/MS2 technique Romanian Doping Control Laboratory, Bucharest, ROMANIA Abstract New substances are added each year to the different classes of substances of WADA’s Prohibited List and have to be included in the test menu of each accredited doping control laboratory. For the analysis of some of these compounds the technique of choice is the LC/MS2 technique. Furthermore, with the decrease of MRPL levels, for stimulants from 500 ng/mL to 100 ng/mL and for narcotics from 200 ng/mL to 50 ng/mL, beginning from the entering in force on 1 January 2013 of the new WADA Technical Document TD2013MRPL, some of the compounds analyzed by the current GC/MS based procedure for stimulants and narcotics needed to be transferred to the LC/MS2 based procedure in order to lower their limit of detection. This paper-work presents the optimal conditions for preparation, separation and identification of new substances introduced to the LC/MS2 technique based procedures during the year 2012. Introduction Liquid chromatography coupled with mass spectrometry is increasingly used in doping control laboratories [1]. The current work presents the optimization of the LC/MS2 detection parameters and the introduction of the prohibited substances in the existent procedures, depending on the characteristics of the studied compounds. The studied compounds are benzthiazide, cyclopenthiazide, cyclothiazide, epitizide, hydroflumethiazide and polythiazide (thiazide diuretic compounds), tramadol and its O-desmethyl metabolite (narcotic compound from the monitoring program [2]), cyclazodone, pentetrazole, prolintane, propylhexedrine and selegiline (stimulants transferred from the GC/MS- to the LC/MS2-based procedure due to the decreasing of the MRPL levels for stimulants and narcotics [3]). -
DIURETICS Diuretics Are Drugs That Promote the Output of Urine Excreted by the Kidneys
DIURETICS Diuretics are drugs that promote the output of urine excreted by the Kidneys. The primary action of most diuretics is the direct inhibition of Na+ transport at one or more of the four major anatomical sites along the nephron, where Na+ reabsorption takes place. The increased excretion of water and electrolytes by the kidneys is dependent on three different processes viz., glomerular filtration, tubular reabsorption (active and passive) and tubular secretion. Diuretics are very effective in the treatment of Cardiac oedema, specifically the one related with congestive heart failure. They are employed extensively in various types of disorders, for example, nephritic syndrome, diabetes insipidus, nutritional oedema, cirrhosis of the liver, hypertension, oedema of pregnancy and also to lower intraocular and cerebrospinal fluid pressure. Therapeutic Uses of Diuretics i) Congestive Heart Failure: The choice of the diuretic would depend on the severity of the disorder. In an emergency like acute pulmonary oedema, intravenous Furosemide or Sodium ethacrynate may be given. In less severe cases. Hydrochlorothiazide or Chlorthalidone may be used. Potassium-sparing diuretics like Spironolactone or Triamterene may be added to thiazide therapy. ii) Essential hypertension: The thiazides usually sever as primary antihypertensive agents. They may be used as sole agents in patients with mild hypertension or combined with other antihypertensives in more severe cases. iii) Hepatic cirrhosis: Potassium-sparing diuretics like Spironolactone may be employed. If Spironolactone alone fails, then a thiazide diuretic can be added cautiously. Furosemide or Ethacrymnic acid may have to be used if the oedema is regractory, together with spironolactone to lessen potassium loss. Serum potassium levels should be monitored periodically. -
Extracts from PRAC Recommendations on Signals Adopted at the 9-12 March 2020 PRAC
6 April 20201 EMA/PRAC/111218/2020 Corr2,3 Pharmacovigilance Risk Assessment Committee (PRAC) New product information wording – Extracts from PRAC recommendations on signals Adopted at the 9-12 March 2020 PRAC The product information wording in this document is extracted from the document entitled ‘PRAC recommendations on signals’ which contains the whole text of the PRAC recommendations for product information update, as well as some general guidance on the handling of signals. It can be found here (in English only). New text to be added to the product information is underlined. Current text to be deleted is struck through. 1. Immune check point inhibitors: atezolizumab; cemiplimab; durvalumab – Tuberculosis (EPITT no 19464) IMFINZI (durvalumab) Summary of product characteristics 4.4. Special warnings and precautions for use Immune-mediated pneumonitis [..] Patients with sSuspected pneumonitis should be evaluated confirmed with radiographic imaging and other infectious and disease-related aetiologies excluded, and managed as recommended in section 4.2. LIBTAYO (cemiplimab) Summary of product characteristics 1 Expected publication date. The actual publication date can be checked on the webpage dedicated to PRAC recommendations on safety signals. 2 A footnote was deleted on 8 April 2020 for the signal on thiazide and thiazide-like diuretics (see page 3). 3 A minor edit was implemented in the product information of the signal on thiazide and thiazide-like diuretics on 5 June 2020 (see page 4). Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020. -
Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01 -
(12) Patent Application Publication (10) Pub. No.: US 2011/0263526 A1 SATYAM (43) Pub
US 20110263526A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0263526 A1 SATYAM (43) Pub. Date: Oct. 27, 2011 (54) NITRICOXIDE RELEASING PRODRUGS OF CD7C 69/96 (2006.01) THERAPEUTICAGENTS C07C 319/22 (2006.01) CD7C 68/02 (2006.01) (75) Inventor: Apparao SATYAM, Mumbai (IN) A6IP 29/00 (2006.01) A6IP 9/00 (2006.01) (73) Assignee: PIRAMAL LIFE SCIENCES A6IP37/08 (2006.01) LIMITED, Mumbai (IN) A6IP35/00 (2006.01) A6IP 25/24 2006.O1 (21) Appl. No.: 13/092.245 A6IP 25/08 308: A6IP3L/04 2006.O1 (22) Filed: Apr. 22, 2011 A6IP3L/2 308: Related U.S. Application Data 39t. O 308: (60) Provisional application No. 61/327,175, filed on Apr. A6IP3/10 (2006.01) 23, 2010. A6IPL/04 (2006.01) A6IP39/06 (2006.01) Publication Classification A6IP3/02 (2006.01) (51) Int. Cl. A6IP 9/06 (2006.01) A 6LX 3L/7072 (2006.01) 39t. W 308: A6 IK3I/58 (2006.01) A6IP II/08 (2006.015 A6 IK3I/55 (2006.01) A63/62 (2006.015 A6 IK 3/495 (2006.01) A6 IK 3/4439 (2006.01) (52) U.S. Cl. ........... 514/50: 514/166; 514/172: 514/217; A6 IK 3L/455 (2006.01) 514/255.04: 514/338; 514/356; 514/412; A6 IK 3/403 (2006.01) 514/420; 514/423: 514/510,536/28.53:540/67; A6 IK 3/404 (2006.01) 540/591; 544/396; 546/273.7: 546/318: 548/452: A6 IK 3/40 (2006.01) 548/500: 548/537; 549/464; 558/275 A6 IK3I/265 (2006.01) C7H 9/06 (2006.01) (57) ABSTRACT CO7I 71/00 (2006.01) CO7D 22.3/26 (2006.01) The present invention relates to nitric oxide releasing pro C07D 295/14 (2006.01) drugs of known drugs or therapeutic agents which are repre CO7D 40/12 (2006.01) sented herein as compounds of formula (I) wherein the drugs CO7D 213/80 (2006.01) or therapeutic agents contain one or more functional groups C07D 209/52 (2006.01) independently selected from a carboxylic acid, an amino, a CO7D 209/26 (2006.01) hydroxyl and a sulfhydryl group. -
Appendix A: Dartnet Design Specifications
Appendix A: DARTNet Design Specifications Note: Prepared by the DARTNet Team, University of Colorado Denver Department of Family Medicine, Contract No. HHSA29020050037I TO2. A- 1 Appendix A Contents Introduction ................................................................................................................................. A-3 Overall Aims ............................................................................................................................... A-4 Technical Overview .................................................................................................................... A-4 Clinical Data Sources .......................................................................................................... A-5 Clinical Decision Support and Data Extraction .................................................................. A-7 Data Mapping With Each EHR........................................................................................... A-9 Grid Based Computing ............................................................................................................... A-9 Data Export and Presentation to the Grid ......................................................................... A-11 Quality Improvement ........................................................................................................ A-15 Data Additions Through Natural Language Processing ................................................... A-15 Directed Point-of-Care Data Collection ................................................................................... -
PAPERS BMJ: First Published As 10.1136/Bmj.297.6641.95 on 9 July 1988
PAPERS BMJ: first published as 10.1136/bmj.297.6641.95 on 9 July 1988. Downloaded from The case for low dose diuretics in hypertension: comparison of low and conventional doses of cyclopenthiazide Gary McVeigh, David Galloway, Dennis Johnston Abstract hypertension. The original observations of Cranston In a double blind placebo controlled randomised et al clearly indicated, however, that these drugs parallel study the antihypertensive activity and showed a flat dose-response relation in reducing arterial adverse biochemical effects of three doses of cyclo- blood pressure and that increased doses caused greater penthiazide were evaluated in patients with mild upset to the biochemical profile.7 Equivalent diuretic essential hypertension that had been recently doses of each of the drugs had similar antihypertensive diagnosed or was being treated with a single drug. effects. Much evidence suggests that the attenuation of After a four week placebo washout period 53 patients the hypotensive response to an increasing dose of with diastolic blood pressures between 90-110 mm diuretic is mediated through a reactive rise in plasma Hg were randomly assigned to 50, 125, or 500 Ftg renin activity and angiotensin II concentration to try to cyclopenthiazide or matching placebo for an eight maintain blood pressure in the face ofincreased sodium week period of treatment. Blood pressure was and water depletion.8'0 measured in thepatients' homes bythe same observer Many deleterious metabolic effects have been every two weeks. Serum urea, electrolytes, urate, associated with the use of thiazide diuretics." 12 The and creatinine concentrations and 24 hour urinary relation with hypokalaemia in particular has provoked sodium excretion were monitored every four weeks much debate since publication of the results of the and serum magnesium concentration and plasma multiple risk factor intervention trial.'3 Analysis of the renin activity at the end ofthe washout and treatment data suggested that a subgroup of patients requiring periods. -
Drugs for Primary Prevention of Atherosclerotic Cardiovascular Disease: an Overview of Systematic Reviews
Supplementary Online Content Karmali KN, Lloyd-Jones DM, Berendsen MA, et al. Drugs for primary prevention of atherosclerotic cardiovascular disease: an overview of systematic reviews. JAMA Cardiol. Published online April 27, 2016. doi:10.1001/jamacardio.2016.0218. eAppendix 1. Search Documentation Details eAppendix 2. Background, Methods, and Results of Systematic Review of Combination Drug Therapy to Evaluate for Potential Interaction of Effects eAppendix 3. PRISMA Flow Charts for Each Drug Class and Detailed Systematic Review Characteristics and Summary of Included Systematic Reviews and Meta-analyses eAppendix 4. List of Excluded Studies and Reasons for Exclusion This supplementary material has been provided by the authors to give readers additional information about their work. © 2016 American Medical Association. All rights reserved. 1 Downloaded From: https://jamanetwork.com/ on 09/28/2021 eAppendix 1. Search Documentation Details. Database Organizing body Purpose Pros Cons Cochrane Cochrane Library in Database of all available -Curated by the Cochrane -Content is limited to Database of the United Kingdom systematic reviews and Collaboration reviews completed Systematic (UK) protocols published by by the Cochrane Reviews the Cochrane -Only systematic reviews Collaboration Collaboration and systematic review protocols Database of National Health Collection of structured -Curated by Centre for -Only provides Abstracts of Services (NHS) abstracts and Reviews and Dissemination structured abstracts Reviews of Centre for Reviews bibliographic -
Penetrating Topical Pharmaceutical Compositions Containing N-\2-Hydroxyethyl\Pyrrolidone
Europaisches Patentamt ® J European Patent Office © Publication number: 0 129 285 Office europeen des brevets A2 (12) EUROPEAN PATENT APPLICATION © Application number: 84200823.7 ©Int CI.3: A 61 K 47/00 A 61 K 31/57, A 61 K 45/06 © Date of filing: 12.06.84 © Priority: 21.06.83 US 506273 © Applicant: THE PROCTER & GAMBLE COMPANY 301 East Sixth Street Cincinnati Ohio 45201 (US) © Date of publication of application: 27.12.84 Bulletin 84/52 © Inventor: Cooper, Eugene Rex 2425 Ambassador Drive © Designated Contracting States: Cincinnati Ohio 4523KUS) BE CH DE FR GB IT LI NL SE © Representative: Suslic, Lydia et al, Procter & Gamble European Technical Center Temseiaan 100 B-1820 Strombeek-Bever(BE) © Penetrating topical pharmaceutical compositions containing N-(2-hydroxyethyl)pyrrolidone. Topical pharmaceutical compositions comprising a pharmaceutically-active agent and a novel, penetration- enhancing vehicle or carrier are disclosed. The vehicle or carrier comprises a binary combination of N-(2-Hydroxyethyl) pyrrolidone and a "cell-envelope disordering compound". The compositions provide marked transepidermal and per- cutaneous delivery of the active selected. A method of treat- ing certain pathologies and conditions responsive to the selected active, systemically or locally, is also disclosed. TECHNICAL FIELD i The present invention relates to compositions which enhance the utility of certain pharmaceutically-active agents by effectively delivering these agents through the integument. Because of the ease of access, dynamics of application, large surface area, vast exposure to the circulatory and lymphatic networks, and non-invasive nature of the treatment, the delivery of pharmaceutically-active agents through the skin has long been a promising concept.