Cardiotoxicity of Non-Cardiovascular Drugs: Minotti/Cardiotoxicity of Non-Cardiovascular Drugs

Content: Chapter 1 Mitochondrial Dysfunction in Cell Injury and Cardiotoxicity (pages 1–23): Fabio Di Lisa, Martina Semenzato, Andrea Carpi, Sara Menazza, Nina Kaludercic, Roberta Menabo and Marcella Canton Chapter 2 Cardiovascular Liabilities of Drugs: Regulatory Aspects (pages 25–45): Claudio Arrigoni Chapter 3 Cellular Mechanisms, Molecular Targets, and Structure–Function Relationships in Drug?Induced Arrhythmias: Antihistamines, Psychoactive Drugs, and Antimicrobial Agents (pages 47–96): Maria Virginia Soldovieri and Maurizio Taglialatela Chapter 4 Cardiovascular Toxicity of Antitumor Drugs: Dimensions of the Problem in Children (pages 97–126): Rebecca Scully and Steven E. Lipshultz Chapter 5 Cardiovascular Toxicity of Antitumor Drugs: Dimension of the Problem in Adult Settings (pages 127–199): Joseph R. Carver and Chaitali J. Desai Chapter 6 Diagnostic Aspects of Cardiovascular Toxicity of Antitumor Drugs (pages 201–221): Michael S. Ewer and Thomas M. Suter Chapter 7 Cardiovascular Toxicity of Antitumor Drugs: Translating Molecular Mechanisms into Clinical Facts (pages 223–256): Pierantonio Menna, Emanuela Salvatorelli, Carlo Salsano, Luca Gianni and Giorgio Minotti Chapter 8 NSAID Action and the Foundations for Cardiovascular Toxicity (pages 257–285): Anna L. Blobaum and Lawrence J. Marnett Chapter 9 Cardiovascular Toxicities of NSAIDS: Epidemiologic Aspects (pages 287–312): Antonio Gonzalez?Perez and Luis Alberto Garcia Rodriguez Chapter 10 Cardiovascular Toxicities of Life?Saving Drugs: Antiviral Therapy (pages 313–332): James J. Kohler and William Lewis Acknowledgements......Page 16 Impairment of Energy Metabolism......Page 18 Impairment of Oxidative Metabolism......Page 19 Alterations in Intramitochondrial and Intracellular [Ca2+]......Page 20 Mitochondria-Derived Oxidative Stress......Page 21 PTP Opening as the Final Effector of Mitochondrial Dysfunction......Page 23 ETC Inhibition......Page 25 Uncoupling of Oxidative Phosphorylation......Page 27 Alternate Redox Reactions......Page 28 Inhibition of Metabolic Pathways......Page 29 Summary......Page 39 QT Correction and QT/RR Analysis......Page 49 Cytotoxic Drugs......Page 52 Drugs for the Treatment of Diabetes Mellitus......Page 53 Conclusions......Page 60 Clinical Evidence......Page 69 Cardiotoxic Antihistamines Block hERG/IKr......Page 72 Clinical Evidence......Page 74 hERG/IKr as Target for Psychotropic Drugs......Page 77 Interaction of Psychotropic Drugs with Other Ion Channels: the Brugada Syndrome......Page 79 Macrolides......Page 82 Fluoroquinolones......Page 84 Antifungals......Page 86 Antimalarials......Page 87 Other Antiprotozoal Agents......Page 89 hERG Channel Structure......Page 90 State-Dependent hERG Blockade......Page 92 Molecular Determinants of hERG Blockade......Page 93 Conclusion......Page 110 Survivorship and Incidence......Page 111 Anthracyclines......Page 112 Mitoxantrone......Page 116 5-Fluorouracil......Page 117 Multidrug Regimens......Page 118 Radiation......Page 119 Dexrazoxane......Page 120 Additional Agents with Cardioprotective Potential......Page 122 Echocardiography......Page 124 Troponins......Page 125 Natriuretic Peptides......Page 126 Highly Sensitive C-Reactive Protein......Page 128 ACE Inhibitors......Page 129 Growth Hormone......Page 130 Summary......Page 140 Epirubicin......Page 146 Liposomal Encapsulation......Page 147 Third Generation Anthracyclines......Page 148 Rituximab......Page 149 Alemtuzumab......Page 150 Trastuzumab......Page 152 Metastatic Breast Cancer Studies......Page 153 Adjuvant Studies......Page 155 Lapatinib......Page 159 Bevacizumab......Page 160 Gemcitabine......Page 163 Fluorouracil 5-FU......Page 164 Capecitabine......Page 166 Histone Deacetylase Inhibitors HDAC......Page 167 Cyclophosphamide......Page 168 Ifosfamide......Page 169 Vinca Alkaloids......Page 170 Taxanes......Page 171 Epilithones......Page 172 Thalidomide......Page 173 Pomalidomide......Page 174 Imatinib......Page 175 Sunitinib......Page 176 Sorafenib......Page 177 Gefitinib......Page 178 Bortezomib......Page 179 Cisplatin......Page 181 Pemtrexed......Page 184 Interleukins......Page 185 New Therapies......Page 186 Arsenic Trioxide......Page 187 Bendamustine......Page 188 Atherosclerotic Risk Factors and Arterial Events......Page 190 Graft versus Host Disease......Page 191 Cardiac Ultrasound......Page 213 Mechanism of Cardiotoxicity......Page 216 The Cumulative-Dose Relationship of Type I Agents......Page 217 The Characteristic Cardiac Structural Abnormalities Associated with Type I Agents......Page 218 The Clinical Spectrum of Cardiotoxicity of Type I Agents......Page 220 Risk Factors that Predict Augmented Toxicity of Type I Agents......Page 224 Mitigation of Cardiotoxicity Associated with Type I Agents......Page 225 Trastuzumab Cardiotoxicity......Page 227 Conclusions......Page 234 General Mechanisms of Anthracycline Cardiotoxicity: Preclinical Models and Clinical Readouts......Page 237 From a Translational Model of Human Heart to Clinical Facts......Page 239 Overall Assessment of the Translational Model of Human Heart and Its Applicability to Research Issues......Page 246 One Step Forward: Anthracyclines in the Spontaneously Hypertensive Rat......Page 249 Another Step Forward: Combining Anthracyclines with Nonanthracycline Chemotherapeutics......Page 250 Towards an Integrated Model of Multiple Hits......Page 253 Trastuzumab: How Could It Pass Preclinical Screens of Cardiovascular Liability?......Page 255 Trastuzumab Cardiotoxicity: A Matter of Two Hits or Multiple Hits?......Page 256 Do We Have a Model to Probe Trastuzumab in a Multiple-Hit Scenario?......Page 257 Summary and Perspectives......Page 268 Conclusions......Page 297 Conclusions......Page 323 Some drugs which are not aimed at treating heart disease have nevertheless been found to have profound effects on heart muscle. Cardiotoxicity is one of the major forms of toxicity seen in drugs and it accounts for most drug recalls and delays experienced in regulatory approvals.In recent years a number of non-cardiac blockbuster drugs such as terfenadine have been withdrawn from major markets because of cardiotoxicity concerns, while other drugs have either been withdrawn prior to marketing or required labelling changes that significantly restricted their use. In Cardiotoxicity of Non-Cardiovascular Drugs international experts describe the molecular mechanisms and clinical read-outs of cardiac events induced by a broad variety of noncardiovascular drugs. Particular emphasis is paid to the preclinical screening of drug cardiotoxicity. Topics include: metabolic targets of cardiotoxicity regulatory aspects translating molecular mechanisms into clinical trials structure-activity relationships in arrhythmias by antihistamines and psychoactive drugs cardiovascular toxicity of antitumor drugs cardiovascular toxicities of non-steroidal anti-inflammatory drugs cardiovascular toxicities of antiretroviral therapies Cardiotoxicity of Non-Cardiovascular Drugs is an essential guide to this important area of drug development. It will find a place on the bookshelves of researchers, regulators and students in medicinal chemistry, drug development, pharmacology, pharmacy and cardiovascular disease. Machine generated contents note: List of Contributors 1. Mitochondrial Dysfunction In Cell Injury and Cardiotoxicity Fabio Di Lisa, Martina Semenzato, Andrea Carpi, Sara Menazza, Nina Kaludercic, Roberta Menabò, Marcella Canton 2. Cardiovascular Liabilities of Drugs: Regulatory Aspects Claudio Arrigoni 3. Cellular Mechanisms, Molecular Targets, and Structure-Function Relationships In Drug-Induced Arrhythmias: The Case Of Antihistamines, Psychoactive Drugs, and Antimicrobial Agents Maria Virginia Soldovieri and Maurizio Taglialatela 4. Cardiovascular Toxicity of Antitumor Drugs: Dimensions of the Problem in Children Rebecca Scully, Louis Pruitt, Steven E. Lipshultz 5. Cardiovascular Toxicity of Antitumor Drugs: Dimension of the Problem in Adult Settings Joseph R. Carver and Chaitali J. Desai 6. Diagnostic Aspects of Cardiovascular Toxicity of Antitumor Drugs Michael S. Ewer, Thomas M. Suter 7. Cardiovascular Toxicity of Antitumor Drugs: Translating Molecular Mechanisms into Clinical Facts Pierantonio Menna, Emanuela Salvatorelli, Carlo Salsano, Luca Gianni*, and Giorgio Minotti 8. NSAID Action and the Foundations for Cardiovascular Toxicity Anna L. Blobaum and Lawrence J. Marnett 9. Cardiovascular toxicities of NSAIDS: Epidemiologic aspects Antonio González-Pe;rez, Luis Alberto Garci;a Rodriguez 10. Cardiovascular Toxicities of Life-Saving Drugs: Antiviral Therapy James J. Kohler & William Lewis. "First book to deal with this important area of adverse drug reactions -- cardiotoxicity is one of the major forms of toxicity seen in drugs and it accounts for most drug recalls and delays experienced in regulatory approvals. Covers four important therapeutic classes: psychoactive drugs; anticancer drugs; non-steroidal anti-inflammatory drugs; and anti-retroviral drugs. - Emphasis on the preclinical screening of drug cardiotoxicity, to enable drug developers to test for this toxicity before starting expensive clinical trials"--Provided by publisher.