Cardiac Pharmacology (eBook)

Front Cover 1
Cardiac Pharmacology 4
Copyright Page 5
Table of Contents 8
Dedication 6
List of Contributors 14
Preface 16
Part I: Intrinsic and Neural Control of Cardiac Function 18
Chapter 1. Regulation of Myocardial Contractility 20
I. Contractility Defined 21
II. Neural Regulation of Cardiac Contractility 24
III. Humoral Regulation of Contractility 32
IV. Autoregulation 34
References 37
Chapter 2. The Nervous System as an Important Site of Action for Drugs Affecting Cardiovascular Function 42
I. Introduction 42
II. Positive Inotropic Agents 44
III. Antiarrhythmic Agents 49
IV. Antihypertensive Agents 52
V. Antianginal Agents 59
VI. The Nervous System as a Target for Developing New and Better Therapies for Cardiovascular Disease 60
References 63
Part II: Pharmacologie Modification of Cardiac Function 68
Chapter 3. Evaluation of Drug-Induced Alterations in Myocardial Contractility 70
I. Introduction 70
II. Conceptual Basis for Indices of Myocardial Contractility 71
III. Indices Obtained during the Isovolumic Phase of Ventricular Systole 78
IV. Indices Obtained during the Ejection Phase of Ventricular Systole 82
V. The Walton-Brodie Strain Gauge Arch 84
VI. Summary 88
References 89
Chapter 4. Cyclic Nucleotides and Cardiac Function 92
I. Cyclic AMP 92
II. Cyclic GMP 96
III. Phosphodiesterase 99
IV. Effects of Hypoxia and Ischemia on Cyclic Nucleotide Content of the Heart 102
V. Cyclic Nucleotides and Coronary Vascular Function 103
VI. Cyclic Nucleotides and Cardiac Metabolism 104
References 108
Chapter 5. Na+, K+-ATPase Activity and Cardiac Glycoside Action 112
I. Introduction 112
II. The Nature of the Enzyme 113
III. Theories on the Mechanism of Action of Cardiac Glycosides 116
IV. Digitalis Toxicity and Na+,K+-ATPase Activity 126
V. Conclusions 127
References 128
Chapter 6. Effects of Digitalis Glycosides on Myocardial Function 130
I. Introduction 130
II. Inotropic Effects of Digitalis Glycosides 132
III. Cardiac Electrophysiologic Effects of Digitalis 136
IV. Digitalis Glycoside Toxicity 139
V. New Directions in Research on Positive Inotropic Agents 140
References 141
Chapter 7. Clinical Pharmacology of Digitalis Glycosides 144
I. Introduction 144
II. Pharmacokinetics of the Digitalis Glycosides 145
III. Serum Levels of Digitalis Glycosides 153
IV. Drug Interactions 160
V. Digitalis Intoxication 161
References 162
Chapter 8. Physiologic and Pharmacologic Basis for the Use of Vasodilators in Heart Failure 166
I. Introduction 167
II. Mechanism of Action of Vasodilators 167
III. Afterload or Impedance Reduction 167
IV. Venodilation 174
V. Improvement in Segmental Myocardial Ischemia 174
VI. Left Ventricular Compliance 175
VII. Pathophysiology of Myocardial Failure 176
VIII. Classification of Vasodilators 178
IX. Hemodynamic Effects of Vasodilators 180
X. Clinical Use of Vasodilators in Heart Failure 
187 
XI. Summary 217
References 218
Part III: Genesis and Control of Cardiac Arrhythmias 224
Chapter 9. Electrophysiologic Evaluation of Potential Antiarrhythmic Drugs 226
I. Introduction 226
II. Instrumentation 227
III. Isolated Tissues 232
IV. Membrane Potentials 236
V. Influence of Drugs and Chemicals on Cardiac Membrane Potentials 241
References 244
Chapter 10. Ëlectrophysiologic Characteristics of Cardiac Cells and the Genesis of Cardiac Arrhythmias 246
I. Introduction 246
II. The Resting Potential of Cardiac Cells 247
III. Action Potentials in Cardiac Cells 255
IV. Effects of Disease on the Electrophysiologic Characteristics of Cardiac Cells 267
V. The Genesis of Cardiac Arrhythmias 271
References 288
Chapter 11. Antiarrhythmic Drugs 292
I. Introduction 293
II. Quinidine, Procainamide, and Disopyramide 293
III. N-Acetylprocainamide 297
IV. Lidocaine, Tocainide, and Mexiletine 298
V. Phenytoin (Diphenylhydation) 302
VI. Propranolol 304
VII. Verapamil 308
VIII. Bretylium 311
IX. Aprindine 312
X. Amiodarone 314
XI. Conclusions 315
References 315
Chapter 12. The Clinical Pharmacology of Antiarrhythmic Drugs 322
I. Introduction 322
II. Pharmacokinetics of Antiarrhythmic Drugs 323
III. Indications and End-Points for Antiarrhythmic Therapy 331
IV. Role of Electrophysiologic Studies to Determine the Efficacy of Antiarrhythmic Drugs 343
V. Blood Levels of Antiarrhythmic Drugs 344
VI. Summary 346
References 346
Part IV: Pharmacologic Modification of Myocardial Oxygen Supply and Demand 
350 
Chapter 13. Myocardial Metabolism 352
I. Introduction 352
II. Control of Carbohydrate Utilization 353
III. Control of Fatty Acid Metabolism 359
IV. Interaction of Glucose and Fatty Acid Utilization 364
V. Effects of Cardiac Work on Substrate Utilization 365
VI. Effects of Hypoxia on Substrate Utilization 366
VII. Effects of Catecholamines on Substrate Utilization 368
VIII. Effects of Insulin on Myocardial Substrate Utilization 370
IX. Summary 371
References 372
Chapter 14. Evaluation of Drug Effects on Coronary Blood Flow and Cardiac Oxygen Consumption 378
I. Choosing the Experimental Model 378
II. Methods for Measuring Coronary Flow 381
III. Collateral Blood Flow Measurements 394
IV. Measure of Myocardial Oxygen Consumption 398
References 400
Chapter 15. ß-Adrenergic Antagonists in Angina and Myocardial Infarction 404
I. The Basis of the Use of ß-Adrenergic Antagonists in Ischemic Heart Disease 405
II. Effect of ß-Adrenergic Antagonists on Coronary Blood Flow 406
III. Effects of ß-Adrenergic Antagonists on the Blood 407
IV. ß-Adrenergic Antagonists in Angina Pectoris 408
V. Division I: Nonselective ß-Adrenergic Antagonists 410
VI. Division II: Cardioselective ß-Adrenergic Antagonists 413
VII. Division III: Nonselective ß-Adrenergic Antagonists a Blockade 414
VIII. Comparison of Adrenergic Blocking Drugs 414
IX. ß-Blocking Drugs in Combination with Other Antianginal Agents 417
X. Withdrawal of ß-Adrenergic Blocking Drugs in Patients with Angina Pectoris 418
XI. Regulation of Dosage of ß-Adrenergic Antagonists in Patients with Angina Pectoris 420
XII. The Value of ß- Adrenoceptor Antagonists in Angina Pectoris 421
XIII. ß-Adrenergic Antagonists in Myocardial Infarction 422
XIV. Conclusion 425
Acknowledgments 426
References 426
Chapter 16. Modification of Myocardial Infarct Size by Drugs: Methods for Measuring Infarct Size and Approach to Patient Care 432
I. The Border Zone 433
II. Techniques for Measuring the Extent of Damage 435
III. Factors That Determine the Outcome of Ischemic Myocardium 444
IV. The Treatment of Potential Detrimental Events 444
V. The Treatment of the Uncomplicated Patient 447
VI. Conclusion: A Word of Caution 450
Acknowledgments 452
References 452
Index 458