Cardiotoxicity of Non-Cardiovascular Drugs

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