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Cardiac Drug Safety : a Bench to Bedside Approach.
Ensuring 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...
| Clasificación: | Libro Electrónico |
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| Autor principal: | |
| Formato: | Electrónico eBook |
| Idioma: | Inglés |
| Publicado: |
Singapore :
World Scientific,
2012.
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| Temas: | |
| Acceso en línea: | Texto completo |
Tabla de Contenidos:
- 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.
- Calcium channelsPotassium 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.
- Chapter 4 The Mechanisms Underlying Cardiac ArrhythmiasIntroduction; Mechanisms Underlying Cardiac Arrhythmias; Abnormal Automaticity; Early and Delayed Afterdepolarizations; 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.
- Arrhythmia Mechanisms and Novel Antiarrhythmic Approaches Identified Using the Hypokalemic Mouse ModelSummary; 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.
- Preclinical Evaluation of Cardiac Drug SafetyThe 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.