In Vitro to in Vivo Extrapolation for Drug-Induced Liver Injury Using a Pair Ranking Method
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Table 2. 2012 AGS Beers Criteria for Potentially
Table 2. 2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults Strength of Organ System/ Recommendat Quality of Recomm Therapeutic Category/Drug(s) Rationale ion Evidence endation References Anticholinergics (excludes TCAs) First-generation antihistamines Highly anticholinergic; Avoid Hydroxyzin Strong Agostini 2001 (as single agent or as part of clearance reduced with e and Boustani 2007 combination products) advanced age, and promethazi Guaiana 2010 Brompheniramine tolerance develops ne: high; Han 2001 Carbinoxamine when used as hypnotic; All others: Rudolph 2008 Chlorpheniramine increased risk of moderate Clemastine confusion, dry mouth, Cyproheptadine constipation, and other Dexbrompheniramine anticholinergic Dexchlorpheniramine effects/toxicity. Diphenhydramine (oral) Doxylamine Use of diphenhydramine in Hydroxyzine special situations such Promethazine as acute treatment of Triprolidine severe allergic reaction may be appropriate. Antiparkinson agents Not recommended for Avoid Moderate Strong Rudolph 2008 Benztropine (oral) prevention of Trihexyphenidyl extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson disease. Antispasmodics Highly anticholinergic, Avoid Moderate Strong Lechevallier- Belladonna alkaloids uncertain except in Michel 2005 Clidinium-chlordiazepoxide effectiveness. short-term Rudolph 2008 Dicyclomine palliative Hyoscyamine care to Propantheline decrease Scopolamine oral secretions. Antithrombotics Dipyridamole, oral short-acting* May -
Inflammatory Bowel Disease Irritable Bowel Syndrome
Inflammatory Bowel Disease and Irritable Bowel Syndrome Similarities and Differences 2 www.ccfa.org IBD Help Center: 888.MY.GUT.PAIN 888.694.8872 Important Differences Between IBD and IBS Many diseases and conditions can affect the gastrointestinal (GI) tract, which is part of the digestive system and includes the esophagus, stomach, small intestine and large intestine. These diseases and conditions include inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). IBD Help Center: 888.MY.GUT.PAIN 888.694.8872 www.ccfa.org 3 Inflammatory bowel diseases are a group of inflammatory conditions in which the body’s own immune system attacks parts of the digestive system. Inflammatory Bowel Disease Inflammatory bowel diseases are a group of inflamma- Causes tory conditions in which the body’s own immune system attacks parts of the digestive system. The two most com- The exact cause of IBD remains unknown. Researchers mon inflammatory bowel diseases are Crohn’s disease believe that a combination of four factors lead to IBD: a (CD) and ulcerative colitis (UC). IBD affects as many as 1.4 genetic component, an environmental trigger, an imbal- million Americans, most of whom are diagnosed before ance of intestinal bacteria and an inappropriate reaction age 35. There is no cure for IBD but there are treatments to from the immune system. Immune cells normally protect reduce and control the symptoms of the disease. the body from infection, but in people with IBD, the immune system mistakes harmless substances in the CD and UC cause chronic inflammation of the GI tract. CD intestine for foreign substances and launches an attack, can affect any part of the GI tract, but frequently affects the resulting in inflammation. -
Therapeutic Class Brand Name P a Status Generic
P A Therapeutic Class Brand Name Status Generic Name Strength Form Absorbable Sulfonamides AZULFIDINE SULFASALAZINE 250MG/5ML ORAL SUSP Absorbable Sulfonamides AZULFIDINE SULFASALAZINE 500MG TABLET Absorbable Sulfonamides AZULFIDINE SULFASALAZINE 500MG TABLET DR Absorbable Sulfonamides BACTRIM DS SULFAMETHOXAZOLE/TRIMETHO 800-160MG TABLET Absorbable Sulfonamides GANTRISIN SULFISOXAZOLE 500MG TABLET Absorbable Sulfonamides GANTRISIN SULFISOXAZOLE ACETYL 500MG/5ML ORAL SUSP Absorbable Sulfonamides GANTRISIN SULFISOXAZOLE ACETYL 500MG/5ML SYRUP Absorbable Sulfonamides SEPTRA SULFAMETHOXAZOLE/TRIMETHO 200-40MG/5 ORAL SUSP Absorbable Sulfonamides SEPTRA SULFAMETHOXAZOLE/TRIMETHO 400-80MG TABLET Absorbable Sulfonamides SULFADIAZINE SULFADIAZINE 500MG TABLET ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 10-20MG CAPSULE ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 2.5-10MG CAPSULE ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 5-10MG CAPSULE ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 5-20MG CAPSULE P A Therapeutic Class Brand Name Status Generic Name Strength Form ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 5-40MG CAPSULE ACE Inhibitor/Calcium Channel Blocker Combination LOTREL AMLODIPINE BESYLATE/BENAZ 10-40MG CAPSULE Acne Agents, Systemic ACCUTANE ISOTRETINOIN 10MG CAPSULE Acne Agents, Systemic ACCUTANE ISOTRETINOIN 20MG CAPSULE Acne Agents, Systemic ACCUTANE -
PROZAC Product Monograph Page 1 of 49 Table of Contents
PRODUCT MONOGRAPH PrPROZAC® fluoxetine hydrochloride 10 mg and 20 mg Capsules Antidepressant / Antiobsessional / Antibulimic © Eli Lilly Canada Inc. Date of Revision: January, 25 Exchange Tower 2021 130 King Street West, Suite 900 PO Box 73 Toronto, Ontario M5X 1B1 1-888-545-5972 www.lilly.ca Submission Control No: 192639 PROZAC Product Monograph Page 1 of 49 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION .......................................................3 SUMMARY PRODUCT INFORMATION...........................................................................3 INDICATIONS AND CLINICAL USE ................................................................................3 CONTRAINDICATIONS .....................................................................................................4 WARNINGS AND PRECAUTIONS ....................................................................................5 ADVERSE REACTIONS ...................................................................................................13 DRUG INTERACTIONS....................................................................................................22 DOSAGE AND ADMINISTRATION ................................................................................27 OVERDOSAGE..................................................................................................................28 ACTION AND CLINICAL PHARMACOLOGY ...............................................................30 STORAGE AND STABILITY............................................................................................32 -
![The Myocardial Metabolic and Haemodynamic Effects of Perhexiline in I]Y Wvo and Nv Vitro Models](https://docslib.b-cdn.net/cover/7158/the-myocardial-metabolic-and-haemodynamic-effects-of-perhexiline-in-i-y-wvo-and-nv-vitro-models-87158.webp)
The Myocardial Metabolic and Haemodynamic Effects of Perhexiline in I]Y Wvo and Nv Vitro Models
THE MYOCARDIAL METABOLIC AND HAEMODYNAMIC EFFECTS OF PERHEXILINE IN I]Y WVO AND NV VITRO MODELS Steven Anthony Unger A Thesis submitted to The University of Adelaide as the requirement for the degree of Doctor of Philosophy The Cardiology Unit, North.Western Adelaide Health Service Department of Medicine, The University of Adelaide. September 2000 u TABLE OF CONTENTS Table of Contents ll Thesis Summary vlt Dcclaration ix Acknowledgments x CHAPTER 1: A LITERATURE REVIEW OF METABOLIC APPROACHES TO MYOCARDIAL ISCHAEMIA I 1.1 INTRODUCTION 2 7.2 CHRONIC MYOCARDIAL ISCHAEMIA 3 1.2.1 Epidemiology 3 1.2.2 Pathogenesis 4 1.3 CARDIAC METABOLISM 7 1.3.1 Overview offatty acid metabolism 8 1.3.1.1 Uptake and transport within the aqueous cytoplasm 8 1.3.1.2 Transport into mitochondria 9 1.3.1.3 B-oxidation l0 1.3.1.4 TCA cycle and electron transport chain 10 1.3.2 Regulation offatty acid metabolism 11 1.3.3 Oventiew of carbohydrate metabolism 13 1.3.4 Regulation of carbohydrate metabolism 14 ' L3.5 Substrate utilisation by the heart: the cost,in oxygen 16 1.3.6 Myocardial metabolism during ischaemia/reperfusion 18 1.3.7 The role offatty acid metabolites 22 1.4 MANAGEMENT OF CHRONIC MYOCARDIAL ISCHAEMIA 24 1.4.1 Medical therapy 24 alaaìf:a--.--nÁ 1.4. i. i i\iüa[es L+ 1.4.1.2 B-adrenoceptor antagonists 25 lrl 1.4.1.3 L-t1pe calcium antagonists 25 1.4.2 Revascularisation 26 1.4.2.1 Percutaneous transluminal coronary angioplasty 26 1.4.2.2 Coronary artery b¡pass surgery 28 I .4.2.3 Transmyocardial laser revascularisation 29 1.4.3 Limitations of current strategies 30 1.5 METABOLIC APPROACHES TO MYOCARDIAL ISCHAEMIA 32 1.5.1 Increasing glucose supply to the heart 35 1.5. -
Predicting Toxicity from Gene Expression with Neural Networks
Predicting Toxicity from Gene Expression with Neural Networks Peter Eastman1 and Vijay S. Pande1 1Department of Bioengineering, Stanford University, Stanford, CA 94305 Abstract We train a neural network to predict chemical toxicity based on gene expression data. The input to the network is a full expression profile collected either in vitro from cultured cells or in vivo from live animals. The output is a set of fine grained predictions for the presence of a variety of pathological effects in treated animals. When trained on the Open TG-GATEs database it produces good results, outperforming classical models trained on the same data. This is a promising approach for efficiently screening chemicals for toxic effects, and for more accurately evaluating drug candidates based on preclinical data. Introduction Predicting toxicity is a vital problem in many fields. One quarter of all drug candidates that reach phase II clinical trials ultimately fail because of toxicity[1]. Better methods to predict this in advance would spare patients from taking drugs that ultimately prove toxic, as well as saving enormous time and money. Toxic effects from industrial and household chemicals are also a major public health problem. Often they are tested only on animals, not humans, but animals can be a poor model for toxicity in humans[2]. Better methods to predict human toxicity would have major public health benefits. Many chemicals cause chronic rather than acute toxicity. It may take months or years for their effects to become apparent. Better methods to spot the early signs of chronic toxicity before clinical symptoms appear would allow clinical trials to be stopped sooner, and also would reduce the risk of toxic effects being missed. -
Prediction of Premature Termination Codon Suppressing Compounds for Treatment of Duchenne Muscular Dystrophy Using Machine Learning
Prediction of Premature Termination Codon Suppressing Compounds for Treatment of Duchenne Muscular Dystrophy using Machine Learning Kate Wang et al. Supplemental Table S1. Drugs selected by Pharmacophore-based, ML-based and DL- based search in the FDA-approved drugs database Pharmacophore WEKA TF 1-Palmitoyl-2-oleoyl-sn-glycero-3- 5-O-phosphono-alpha-D- (phospho-rac-(1-glycerol)) ribofuranosyl diphosphate Acarbose Amikacin Acetylcarnitine Acetarsol Arbutamine Acetylcholine Adenosine Aldehydo-N-Acetyl-D- Benserazide Acyclovir Glucosamine Bisoprolol Adefovir dipivoxil Alendronic acid Brivudine Alfentanil Alginic acid Cefamandole Alitretinoin alpha-Arbutin Cefdinir Azithromycin Amikacin Cefixime Balsalazide Amiloride Cefonicid Bethanechol Arbutin Ceforanide Bicalutamide Ascorbic acid calcium salt Cefotetan Calcium glubionate Auranofin Ceftibuten Cangrelor Azacitidine Ceftolozane Capecitabine Benserazide Cerivastatin Carbamoylcholine Besifloxacin Chlortetracycline Carisoprodol beta-L-fructofuranose Cilastatin Chlorobutanol Bictegravir Citicoline Cidofovir Bismuth subgallate Cladribine Clodronic acid Bleomycin Clarithromycin Colistimethate Bortezomib Clindamycin Cyclandelate Bromotheophylline Clofarabine Dexpanthenol Calcium threonate Cromoglicic acid Edoxudine Capecitabine Demeclocycline Elbasvir Capreomycin Diaminopropanol tetraacetic acid Erdosteine Carbidopa Diazolidinylurea Ethchlorvynol Carbocisteine Dibekacin Ethinamate Carboplatin Dinoprostone Famotidine Cefotetan Dipyridamole Fidaxomicin Chlormerodrin Doripenem Flavin adenine dinucleotide -
Ibuprofen: Pharmacology, Therapeutics and Side Effects
Ibuprofen: Pharmacology, Therapeutics and Side Effects K.D. Rainsford Ibuprofen: Pharmacology, Therapeutics and Side Effects K.D. Rainsford Biomedical Research Centre Sheffield Hallam University Sheffield United Kingdom ISBN 978 3 0348 0495 0 ISBN 978 3 0348 0496 7 (eBook) DOI 10.1007/978 3 0348 0496 7 Springer Heidelberg New York Dordrecht London Library of Congress Control Number: 2012951702 # Springer Basel 2012 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. -
Design, Synthesis, and Evaluation of Antiepileptic Compounds Based on Β-Alanine and Isatin
Design, Synthesis, and Evaluation of Antiepileptic Compounds Based on β-Alanine and Isatin by Robert Philip Colaguori A thesis submitted in conformity with the requirements for the degree of Master of Science Department of Pharmaceutical Sciences University of Toronto © Copyright by Robert Philip Colaguori, 2016 ii Design, Synthesis, and Evaluation of Antiepileptic Compounds Based on β-Alanine and Isatin Robert Philip Colaguori Master of Science Department of Pharmaceutical Sciences University of Toronto 2016 Abstract Epilepsy is the fourth-most common neurological disorder in the world. Approximately 70% of cases can be controlled with therapeutics, however 30% remain pharmacoresistant. There is no cure for the disorder, and patients affected are subsequently medicated for life. Thus, there is a need to develop compounds that can treat not only the symptoms, but also delay/prevent progression. Previous work resulted in the discovery of NC-2505, a substituted β-alanine with activity against chemically induced seizures. Several N- and α-substituted derivatives of this compound were synthesized and evaluated in the kindling model and 4-AP model of epilepsy. In the kindling model, RC1-080 and RC1-102 were able to decrease the mean seizure score from 5 to 3 in aged mice. RC1-085 decreased the interevent interval by a factor of 2 in the 4-AP model. Future studies are focused on the synthesis of further compounds to gain insight on structure necessary for activity. iii Acknowledgments First and foremost, I would like to thank my supervisor Dr. Donald Weaver for allowing me to join the lab as a graduate student and perform the work ultimately resulting in this thesis. -
Analysis of Synthetic Chemical Drugs in Adulterated Chinese Medicines by Capillary Electrophoresis/ Electrospray Ionization Mass Spectrometry
RAPID COMMUNICATIONS IN MASS SPECTROMETRY Rapid Commun. Mass Spectrom. 2001; 15: 1473±1480 Analysis of Synthetic chemical drugs in adulterated Chinese medicines by capillary electrophoresis/ electrospray ionization mass spectrometry Hsing Ling Cheng, Mei-Chun Tseng, Pei-Lun Tsai and Guor Rong Her* Department of Chemistry, National Taiwan University, Taipei, Taiwan, R.O.C. Received 20 April 2001; Revised 20 June 2001; Accepted 21 June 2001 Sixteen synthetic chemical drugs, often found in adulterated Chinese medicines, were studied by capillary electrophoresis/UV absorbance CE/UV)and capillary electrophoresis/electrospray ioniza- tion mass spectrometry CE/ESI-MS). Only nine peaks were detected with CZE/UV, but on-line CZE/ MS provided clear identification for most compounds. For a real sample of a Chinese medicinal preparation, a few adulterants were identified by their migration times and protonated molecular ions. For coeluting compounds, more reliable identification was achieved by MS/MS in selected reaction monitoring mode. Micellar electrokinetic chromatography MEKC)using sodium dodecyl sulfate SDS)provided better separation than capillary zone electrophoresis CZE),and, under optimal conditions, fourteen peaks were detected using UV detection. In ESI, the interference of SDS was less severe in positive ion mode than in negative ion mode. Up to 20 mM SDS could be used in direct coupling of MEKC with ESI-MS if the mass spectrometer was operated in positive ion mode. Because of better resolution in MEKC, adulterants can be identified without the use of MS/MS. Copyright # 2001 John Wiley & Sons, Ltd. The use of Chinese medicines to maintain human health and provide the main basis for identification,generally lack the to cure disease has a long and rich history. -
MRI Evidence That Glibenclamide Reduces Acute Lesion Expansion in a Rat Model of Spinal Cord Injury
Spinal Cord (2013) 51, 823–827 OPEN & 2013 International Spinal Cord Society All rights reserved 1362-4393/13 www.nature.com/sc ORIGINAL ARTICLE MRI evidence that glibenclamide reduces acute lesion expansion in a rat model of spinal cord injury JM Simard1,2,3, PG Popovich4, O Tsymbalyuk1, J Caridi1, RP Gullapalli5, MJ Kilbourne6 and V Gerzanich1 Study design: Experimental, controlled, animal study. Objectives: To use non-invasive magnetic resonance imaging (MRI) to corroborate invasive studies showing progressive expansion of a hemorrhagic lesion during the early hours after spinal cord trauma and to assess the effect of glibenclamide, which blocks Sur1-Trpm4 channels implicated in post-traumatic capillary fragmentation, on lesion expansion. Setting: Baltimore. Methods: Adult female Long–Evans rats underwent unilateral impact trauma to the spinal cord at C7, which produced ipsilateral but not contralateral primary hemorrhage. In series 1 (six control rats and six administered glibenclamide), hemorrhagic lesion expansion was characterized using MRI at 1 and 24 h after trauma. In series 2, hemorrhagic lesion size was characterized on coronal tissue sections at 15 min (eight rats) and at 24 h after trauma (eight control rats and eight administered glibenclamide). Results: MRI (T2 hypodensity) showed that lesions expanded 2.3±0.33-fold (Po0.001) during the first 24 h in control rats, but only 1.2±0.07-fold (P40.05) in glibenclamide-treated rats. Measuring the areas of hemorrhagic contusion on tissue sections at the epicenter showed that lesions expanded 2.2±0.12-fold (Po0.001) during the first 24 h in control rats, but only 1.1±0.05-fold (P40.05) in glibenclamide-treated rats. -
Skeletal Muscle Relaxants Review 12/17/2008
Skeletal Muscle Relaxants Review 12/17/2008 Copyright © 2007 - 2008 by Provider Synergies, L.L.C. All rights reserved. Printed in the United States of America. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, digital scanning, or via any information storage and retrieval system without the express written consent of Provider Synergies, L.L.C. All requests for permission should be mailed to: Attention: Copyright Administrator Intellectual Property Department Provider Synergies, L.L.C. 5181 Natorp Blvd., Suite 205 Mason, Ohio 45040 The materials contained herein represent the opinions of the collective authors and editors and should not be construed to be the official representation of any professional organization or group, any state Pharmacy and Therapeutics committee, any state Medicaid Agency, or any other clinical committee. This material is not intended to be relied upon as medical advice for specific medical cases and nothing contained herein should be relied upon by any patient, medical professional or layperson seeking information about a specific course of treatment for a specific medical condition. All readers of this material are responsible for independently obtaining medical advice and guidance from their own physician and/or other medical professional in regard to the best course of treatment for their specific medical condition. This publication, inclusive of all forms contained herein, is intended to