LEADER 05257nam 2200649 a 450 001 9910451573503321 005 20200520144314.0 010 $a1-280-66922-5 010 $a9786613646156 010 $a981-4317-46-2 035 $a(CKB)2550000000101695 035 $a(EBL)919080 035 $a(OCoLC)794328376 035 $a(SSID)ssj0000654806 035 $a(PQKBManifestationID)12321756 035 $a(PQKBTitleCode)TC0000654806 035 $a(PQKBWorkID)10674483 035 $a(PQKB)11268532 035 $a(MiAaPQ)EBC919080 035 $a(WSP)00007839 035 $a(Au-PeEL)EBL919080 035 $a(CaPaEBR)ebr10563572 035 $a(CaONFJC)MIL364615 035 $a(EXLCZ)992550000000101695 100 $a20120607d2012 uy 0 101 0 $aeng 135 $aurcuu|||uu||| 181 $ctxt 182 $cc 183 $acr 200 10$aCardiac drug safety$b[electronic resource] $ea bench to bedside approach /$fMatthew J. Killeen 210 $aSingapore $cWorld Scientific Pub. Co.$d2012 215 $a1 online resource (189 p.) 300 $aDescription based upon print version of record. 311 $a981-4317-45-4 320 $aIncludes bibliographical references and index. 327 $aContents; Foreword; "Et causae quoque aestimatio saepe morbum solvit"* [Celsus: Prooemium 69, De Medicina]; Preface; Chapter 1 Challenges Facing the Pharmaceutical Industry in the 21st Century; Introduction; The Impact of Cardiac Toxicity on the Pharmaceutical Industry; References; Chapter 2 The Cellular Basis of Cardiac Electrophysiology; Introduction; The Initiation of the Heart Beat; The Ventricular Cardiac Action Potential; The Relationship Between the Cardiac Action Potential and the Electrocardiogram; Ion Channels Underlying the Cardiac Action Potential; Sodium channels 327 $aCalcium channels Potassium channels; Cardiac potassium channels; The transient outward potassium channel; Delayed rectifier potassium channels; The ultra rapid delayed rectifier potassium channel; The HERG potassium channel; The slowly activating delayed rectifier potassium channel; Inwardly rectifying potassium channels; Species-dependent variability of potassium channels; Potassium channel subunits; Summary; References; Chapter 3 Clinical Arrhythmia Syndromes; Introduction; The Long QT Syndrome; Congenital Long QT Syndrome; Drug-Induced QT Prolongation; Summary; References 327 $aChapter 4 The Mechanisms Underlying Cardiac Arrhythmias Introduction; Mechanisms Underlying Cardiac Arrhythmias; Abnormal Automaticity; Early and Delayed After depolarizations; Re-entry; Transmural Dispersion of Repolarization; How does Action Potential and QT Prolongation Generate Arrhythmias?; Does the M-Cell Play a Role in Arrhythmia Induction in Humans?; Using Mouse Models to Study Arrhythmia Mechanisms; Experimental Studies Exploring the Relationship Between Changes in Transmural Repolarization Gradients and Arrhythmias in Mouse Hearts 327 $aArrhythmia Mechanisms and Novel Antiarrhythmic Approaches Identified Using the Hypokalemic Mouse Model Summary; References; Chapter 5 The Mechanisms Underlying Drug-Induced Arrhythmias; Introduction; The Classical Model of Drug-Induced QT Prolongation and Proarrhythmia: HERG Blockade; Additional Mechanisms Contributing to Drug-Induced Arrhythmias; Drug-Induction Activation of Depolarizing Ion Channels; Drug-Induced Changes in Ion Channel Expression; Drug-Induced Sodium Channel Dysfunction; Summary; References; Chapter 6 Assessing Cardiac Safety in Drug Development; Introduction 327 $aPreclinical Evaluation of Cardiac Drug Safety The ICH S7B Guidelines; Single Cell Safety Studies; The Purkinje Fiber Model; The Ventricular Wedge Model; Isolated Heart Models; In Vivo Models; The Impact of Species-Related Differences in Cardiac Electrophysiology on Preclinical Drug Safety Assessment; Methods to Provoke Arrhythmias in Preclinical Studies; Programmed electrical stimulation; Reductions in the extracellular K+ concentration; Clinical Evaluation of Cardiac Safety; The Thorough QT study; Thorough QT study design; Additional Biomarkers to Detect Drug-Induced Proarrhythmia 327 $aVariability of repolarization 330 $aEnsuring the safety of new medical products remains a major challenge for the pharmaceutical industry. Cardiac safety, particularly drug-induced heart rhythm abnormalities, remains an important cause of pipeline attrition and has resulted in countless major product recalls or label changes. The risk of encountering this major adverse event continues to shape the drug development and regulatory landscape. Extensive research over the past decade has shed light on the root causes of arrhythmias that are triggered by medications and has helped drive, and optimize, drug safety testing.However, 606 $aCardiovascular agents 608 $aElectronic books. 615 0$aCardiovascular agents. 676 $a363.738/74 676 $a363.73874 676 $a615.71 700 $aKilleen$b Matthew J$0857968 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910451573503321 996 $aCardiac drug safety$91915587 997 $aUNINA LEADER 01339nam 2200433 450 001 9910819208903321 005 20240131171257.0 010 $a1-5275-4206-8 035 $a(CKB)4100000009670254 035 $a(MiAaPQ)EBC5966765 035 $a(OCoLC)1183030600 035 $a(FlNmELB)ELB124312 035 $a(EXLCZ)994100000009670254 100 $a20191126d2019 uy 0 101 0 $aeng 135 $aurcnu|||||||| 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 10$aEco-neurobiology, and how the environment shapes our brains /$fby Andreas M. Grabrucker 210 1$aNewcastle-upon-Tyne :$cCambridge Scholars Publishing,$d2019. 215 $a1 online resource (156 pages) 311 $a1-5275-4035-9 320 $aIncludes bibliographical references and index. 606 $aBrain$xPhysiology 606 $aNature and nurture 606 $aHuman genetics$xVariation 615 0$aBrain$xPhysiology. 615 0$aNature and nurture. 615 0$aHuman genetics$xVariation. 676 $a612.82 700 $aGrabrucker$b Andreas M.$01103305 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910819208903321 996 $aEco-neurobiology, and how the environment shapes our brains$93997160 997 $aUNINA