Cardiac Pharmacology

List of Contributors

Preface

I Intrinsic and Neural Control of Cardiac Function


1 Regulation of Myocardial Contractility

I. Contractility Defined

II. Neural Regulation of Cardiac Contractility

III. Humoral Regulation of Contractility

IV. Autoregulation

References


2 The Nervous System as an Important Site of Action for Drugs Affecting Cardiovascular Function

I. Introduction

II. Positive Inotropic Agents

III. Antiarrhythmic Agents

IV. Antihypertensive Agents

V. Antianginal Agents

VI. The Nervous System as a Target for Developing New and Better Therapies for Cardiovascular Disease

References

II Pharmacologic Modification of Cardiac Function


3 Evaluation of Drug-Induced Alterations in Myocardial Contractility

I. Introduction

II. Conceptual Basis for Indices of Myocardial Contractility

III. Indices Obtained During the Isovolumic Phase of Ventricular Systole

IV. Indices Obtained During the Ejection Phase of Ventricular Systole

V. The Walton-Brodie Strain Gauge Arch

VI. Summary

References


4 Cyclic Nucleotides and Cardiac Function

I. Cyclic AMP

II. Cyclic GMP

III. Phosphodiesterase

IV. Effects of Hypoxia and Ischemia on Cyclic Nucleotide Content of the Heart

V. Cyclic Nucleotides and Coronary Vascular Function

VI. Cyclic Nucleotides and Cardiac Metabolism

References


5 Na+, K+-ATPase Activity and Cardiac Glycoside Action

I. Introduction

II. The Nature of the Enzyme

III. Theories on the Mechanism of Action of Cardiac Glycosides

IV. Digitalis Toxicity and Na+, K+-ATPase Activity

V. Conclusions

References


6 Effects of Digitalis Glycosides on Myocardial Function

I. Introduction

II. Inotropic Effects of Digitalis Glycosides

III. Cardiac Electrophysiologic Effects of Digitalis

IV. Digitalis Glycoside Toxicity

V. New Directions in Research on Positive Inotropic Agents

References


7 Clinical Pharmacology of Digitalis Glycosides

I. Introduction

II. Pharmacokinetics of the Digitalis Glycosides

III. Serum Levels of Digitalis Glycosides

IV. Drug Interactions

V. Digitalis Intoxication

References


8 Physiologic and Pharmacologic Basis for the Use of Vasodilators in Heart Failure

I. Introduction

II. Mechanism of Action of Vasodilators

III. Afterload or Impedance Reduction

IV. Venodilation

V. Improvement in Segmental Myocardial Ischemia

VI. Left Ventricular Compliance

VII. Pathophysiology of Myocardial Failure

VIII. Classification of Vasodilators

IX. Hemodynamic Effects of Vasodilators

X. Clinical Use of Vasodilators in Heart Failure and Myocardial Infarction

XI. Summary

References

III Genesis and Control of Cardiac Arrhythmias


9 Electrophysiologic Evaluation of Potential Antiarrhythmic Drugs

I. Introduction

II. Instrumentation

III. Isolated Tissues

IV. Membrane Potentials

V. Influence of Drugs and Chemicals on Cardiac Membrane Potentials

References


10 Electrophysiologic Characteristics of Cardiac Cells and the Genesis of Cardiac Arrhythmias

I. Introduction

II. The Resting Potential of Cardiac Cells

III. Action Potentials in Cardiac Cells

IV. Effects of Disease on the Electrophysiologic Characteristics of Cardiac Cells

V. The Genesis of Cardiac Arrhythmias

References


11 Antiarrhythmic Drugs

I. Introduction

II. Quinidine, Procainamide, and Disopyramide

III. N-Acetylprocainamide

IV. Lidocaine, Tocainide, and Mexiletine

V. Phenytoin (Diphenylhydation)

VI. Propranolol

VII. Verapamil

VIII. Bretylium

IX. Aprindine

X. Amiodarone

XI. Conclusions

References


12 The Clinical Pharmacology of Antiarrhythmic Drugs

I. Introduction

II. Pharmacokinetics of Antiarrhythmic Drugs

III. Indications and End-Points for Antiarrhythmic Therapy

IV. Role of Electrophysiologic Studies to Determine the Efficacy of Antiarrhythmic Drugs

V. Blood Levels of Antiarrhythmic Drugs

VI. Summary

References

IV Pharmacologic Modification of Myocardial Oxygen Supply and Demand


13 Myocardial Metabolism

I. Introduction

II. Control of Carbohydrate Utilization

III. Control of Fatty Acid Metabolism

IV. Interaction of Glucose and Fatty Acid Utilization

V. Effects of Cardiac Work on Substrate Utilization

VI. Effects of Hypoxia on Substrate Utilization

VII. Effects of Catecholamines on Substrate Utilization

VIII. Effects of Insulin on Myocardial Substrate Utilization

IX. Summary

References


14 Evaluation of Drug Effects on Coronary Blood Flow and Cardiac Oxygen Consumption

I. Choosing the Experimental Model

II. Methods for Measuring Coronary Flow

III. Collateral Blood Flow Measurements

IV. Measure of Myocardial Oxygen Consumption

References


15 β-Adrenergic Antagonists in Angina and Myocardial Infarction

I. The Basis of the Use of β-Adrenergic Antagonists in Ischemic Heart Disease

II. Effect of β-Adrenergic Antagonists on Coronary Blood Flow

III. Effects of β-Adrenergic Antagonists on the Blood

IV. β-Adrenergic Antagonists in Angina Pectoris

V. Division I: Nonselective β-Adrenergic Antagonists

VI. Division II: Cardioselective β-Adrenergic Antagonists

VII. Division III: Nonselective β-Adrenergic Antagonists Plus α Blockade

VIII. Comparison of Adrenergic Blocking Drugs

IX. β-Blocking Drugs in Combination with Other Antianginal Agents

X. Withdrawal of β-Adrenergic Blocking Drugs in Patients with Angina Pectoris

XI. Regulation of Dosage of β-Adrenergic Antagonists in Patients with Angina Pectoris

XII. The Value of β- Adrenoceptor Antagonists in Angina Pectoris

XIII. β-Adrenergic Antagonists in Myocardial Infarction

XIV. Conclusion

References


16 Modification of Myocardial Infarct Size by Drugs: Methods for Measuring Infarct Size and Approach to Patient Care

I. The Border Zone

II. Techniques for Measuring the Extent of Damage

III. Factors That Determine the Outcome of Ischemic Myocardium

IV. The Treatment of Potential Detrimental Events

V. The Treatment of the Uncomplicated Patient

VI. Conclusion: A Word of Caution

References

Index