عنوان

Clinical Pharmacology of Antianginal Drugs

3642695264

9783642695261

b551428

Clinical Pharmacology of Antianginal Drugs

[Book]

U Abshagen

Berlin Springer Berlin

2013

XVI, 552 Seiten in 1 Teil 81 Figuren XVI, 552 Seiten . 244 x 170 mm

Handbook of Experimental Pharmacology, 76

General Principles.- 1 Epidemiology of Ischemic Heart Disease With 5 Figures.- A. Preface.- B. Multiple Risk Factor Intervention Trial.- I. Methods, Eligibility, Intervention Strategies, Randomization.- II. Results and Interpretations.- III. Comments.- IV. Multiple Risk Factor Intervention in North Karelia.- V. The WHO European Collaborative Trial.- VI. The Oslo Trial (Primary Prevention).- C. Epidemiologic Observations Confirming the Trend of Decreasing Coronary Mortality in the United States.- I. Food Consumption Pattern: United States and Germany.- II. Development in England.- III. Life Expectancy in the United States.- IV. Life-Style Changes Versus Improved Medical-Surgical Care.- V. The Rochester Study.- VI. The Minneapolis Study.- VII. The Chicago Peoples Gas Company Study.- VIII. Pathologic-Anatomic Proof that Coronary Atherosclerosis is Decreasing.- D. Hypertension and Hypercholesterolemia: Unifactorial Intervention for the Prevention of Ischemic Heart Disease.- I. Prevention of Fatal and Nonfatal Ischemic Heart Disease Through Unifactorial Intensive Drug Therapy of Hypertension.- II. Results.- III. Prevention of Myocardial Infarction Through Unifactorial Treatment of Hypercholesterolemia.- IV. Summary.- E. Cigarette Smoking and Obesity: Unifactorial Intervention.- I. Smoking.- II. Obesity.- References.- 2 Pathophysiology of Coronary Circulation and of Acute Coronary Insufficiency With 11 Figures.- A. Regulation of Coronary Blood Flow.- I. Overview.- II. Metabolic Autoregulation and the Adenosine Hypothesis.- III. Alternative Hypotheses Explaining Metabolic Autoregulation.- B. Coronary Artery Stenosis and Spasm.- I. Overview.- II. Influence of a Coronary Stenosis on Myocardial Perfusion.- C. Influence of Underperfusion on the Myocardium.- I. Influence on Substrate Metabolism.- II. Influence on High Energy Phosphates.- III. Regional Contractility and Nucleotides in Reperfused Myocardium.- IV. Effect of Regional Ischemia on Local Myocardial Function.- D. Myocardial Infarction.- I. Mechanisms Leading to Cell Death.- II. Reduction of Infarct Size as a Therapeutic Goal.- References.- 3 Pharmacodynamic Principles of Action of Antianginal Drugs.- A. Introduction.- B. The Principles of "Unloading" the Heart.- C. Groups of "Unloading Substances".- D. The Vasospastic Concept.- E. Concepts Underlying Inhibition of Platelet Aggregation.- F. Conclusion.- I. The Augmentation of Oxygen and Substrate Supply to the Heart.- II. Reduction of Myocardial Oxygen Demand: Improvement in the Economy of Cardiac Performance.- Test Methods.- 4 Experimental Testing of Antianginal Drugs in Animals.- A. General Considerations.- B. Measurement of Relevant Parameters.- I. Myocardial Blood Flow.- II. Myocardial Metabolism.- III. Myocardial Function.- IV. Electrocardiogram.- V. Signal Transmission.- C. Experimental Models.- I. Isolated Perfused Hearts.- II. Myocardial Underperfusion and Angina Pectoris.- III. Myocardial Infarction.- IV. Collateral Circulation.- V. Reperfusion and Retroperfusion.- D. Summary.- References.- 5 Noninvasive Methods: Systolic Time Intervals and Echocardiography With 2 Figures.- A. Introduction.- B. Systolic Time Intervals.- I. Measurement of Systolic Time Intervals.- II. General Points.- III. Determinants of the Systolic Time Intervals.- IV. Validation of Systolic Time Intervals.- V. Use of Systolic Time Intervals to Study Drug Action with Antianginal Preparations.- VI. Place of Systolic Time Intervals in Clinical Pharmacology.- C. The Use of M-Mode Echocardiography in Assessing Antianginal Drugs.- I. Technique of Recording.- II. Technique of Measurement.- III. Reproducibility of Dimension Measurements.- IV. Derived Quantities.- V. Computed Quantities.- VI. Effect of Physiological Manoeuvres.- VII. Effects of Drugs.- D. Conclusions.- 6 Peripheral Circulation With 6 Figures.- A. Assessment of Antianginal Drugs Through Studies of the Peripheral Circulation.- B. The Use of Human Subjects for Studies on the Peripheral Circulation.- I. Anatomical Considerations.- II. Ethical Considerations.- C. Administration of the Test Drug.- I. Oral Administration.- II. Intravenous Administration.- III. Intra-arterial Administration.- IV. Percutaneous Administration.- D. Measurement of Blood Flow in the Peripheral Circulation.- I. Venous Occlusion Plethysmography.- II. Strain-Gauge Plethysmography.- III. Thermal Methods.- IV. Pulse Volume Methods.- V. Isotope Clearance Methods.- VI. Differentiation Between Skin and Muscle Blood Flow.- VII. Ultrasonic Flow Meters.- E. Measurement of Venous Tone.- I. Volume Measurement at Constant Pressure.- II. Pressure Measurement at Constant Volume.- III. Vein Diameter Measurement.- F. Measurement of Vascular Permeability.- References.- 7 Exercise Testing With 3 Figures.- A. Introduction.- B. Value of Stress Testing in Asymptomatic Subjects.- C. Value of Stress Testing in Epidemiology.- D. Indications for Exercise Testing.- E. Safety of Stress Testing.- I. Arrhythmias.- II. Hypotension.- F. The Use of Stress Testing in the Evaluation of Therapy in Patients with Ischaemic Heart Diseases.- G. Gardiac Response to Exercise.- H. ECG Response to Exercise.- J. Evaluation of the Effects of Therapy.- I. Nitrates.- II. ?-Adrenergic Blocking Drugs.- III. Calcium Channel Blocking Drugs.- K. Training.- L. Summary.- References.- 8 Radionuclide Methods With 17 Figures.- A. Clinical and Pathophysiologic Aspects of Testing Antiangial Drugs with Radionuclides.- B. Some Important Definitions in Nuclear Medicine.- C. Fundamentals of Nuclear Cardiology.- I. Radionuclide Procedures for Imaging of Myocardial Perfusion..- II. Radionuclide Procedures for Imaging of Myocardial Metabolism.- III. Failures of Myocardial Function.- IV. Failures of the Conduction System of the Heart and Techniques for Their Imaging.- D. Application of Radionuclides for Testing Antianginal Drugs.- I. ?-Blockers.- II. Vasodilators.- References.- 9 Assessment of Coronary Artery Disease and Myocardial Ischemia by Invasive Methods With 18 Figures.- A. Parameters for the Assessment of Cardiac Function in Ischemic Heart Disease.- I. Introduction.- II. Technical Aspects.- III. Hemodynamic Monitoring.- IV. Parameters to Evaluate Cardiac Loading Condition.- B. Assessment of Functional Significance of Coronary Artery Disease..- I. Indications for Coronary Arteriography.- II. Information Gained from Coronary Angiography.- III. Techniques of Coronary Arteriography.- IV. Risks and Complications.- C. Quantitative Approach to Coronary Artery Disease by Invasive Methods.- I. Introduction.- II. Assessment of Left Ventricular Function.- III. Assessment of Coronary Artery Morphology.- IV. Coronary Artery Spasm.- V. Cardiac Metabolism in Ischemia.- D. Invasive Techniques in Therapy.- I. Intracoronary Thrombolysis in Acute Coronary Thrombosis...- II. Percutaneous Transluminal Coronary Angioplasty.- References.- Types of Antianginal Drugs.- 10 Organic Nitrates With 3 Figures.- A. Introduction.- B. Pharmacokinetics of Organic Nitrates.- I. Trinitroglycerin.- II. Isosorbide Dinitrate.- III. Isosorbide-5-mononitrate.- IV. Pentaerythrityl Tetranitrate.- V. Pentaerythrityl Trinitrate.- C. Mechanism of Action at the Molecular Level.- I. Influence on Electrolytes.- II. Influence on Cyclic Nucleotides.- III. Influence on Prostaglandin Metabolism.- D. Mechanism of Acute Antianginal Efficacy.- I. Peripheral Haemodynamic Effects.- II. Effects on Central Haemodynamics and Myocardial Oxygen Consumption.- III. Effects on Myocardial Blood Flow.- IV. Influence of Organic Nitrates on Contractility and Left Ventricular Performance.- V. Chronotropic and Antiarrhythmic Effects.- E. Problems of Long-Term Treatment.- I. Nitrate Tolerance.- II. Nitrate Dependence.- F. Efficacy, Routes of Administration, Formulations and Dosages.- I. Stable Angina.- II. Unstable Angina and Variant Angina.- References.- 11 Molsidomine With 4 Figures.- A. Chemistry - Physicochemical Properties.- B. Metabolism - Kinetics.- I.

Metabolism and Kinetics in Animals.- II. Metabolism and Kinetics in Humans.- C. Pharmacology.- I. Cardiovascular Pharmacology.- II. Studies in Isolated Systems.- D. Clinical Pharmacology.- I. Hemodynamic Studies.- II. Side Effects.- III. Effects on Thrombocyte Aggregation In Vivo.- IV. Effects in Hypertensive Patients.- References.- 12 ?-Adrenoceptor Blocking Agents..- A. Introduction.- B. Pharmacodynamics.- I. Classification of Blocking Drugs.- II. The Associated Properties of jS-Blocking Drugs.- III. Blockade of Exogenous Adrenoceptor Stimulation.- IV. Blockade of Endogenous Adrenergic Stimulation.- V. Response to Physiological Stimuli in Patients Treated with S-Blocking Drugs.- VI. Peripheral Resistance and Peripheral Blood Flow.- VII. Veins.- VIII. Regional Blood Flow.- IX. Bronchial Smooth Muscle.- X. Lipid Metabolism.- XI. Glucose Metabolism.- XII. Noradrenaline and Adrenaline.- XIII. Renin Blocking Activity.- XIV. Stimulation of Vasodilator Prostaglandins.- C. Pharmacokinetics.- I. Absorption and Metabolism.- II. Transport and Distribution.- III. Elimination.- D. Basis for the Use of ?-Antagonists in Ischaemic Disease.- I. Haemodynamic Effects and Oxygen Consumption.- II. Effect of ?-Blockade on Coronary Blood Flow.- III. Myocardial Metabolism.- IV. Effect of ?-Blocking Drugs on the Blood.- V. Cardiac Arrhythmias.- VI. Mode of Action of ?-Blocking Drugs in Angina.- E. Clinical Use of ?-Adrenergic Blocking Drugs.- I. Division I: Nonselective ?-Blocking Drugs.- II. Division II: Cardioselective Blocking Drugs.- III. Division III: Nonselective ?-Blockade plus a-Blockade.- IV. j8-Blocking Drugs in Combination with Nitrates.- V. J-Blocking Drugs in Combination with Calcium Antagonists.- VI. Comparison of Adrenergic Blocking Drugs.- VII. Comparison with Other Treatment.- VIII. Regulation of Dose in Patients with Angina Pectoris.- IX. Indications for ?-Blockade.- X. Withdrawal of ?-Blocking Drugs.- F. Side Effects.- I. Cardiovascular Side Effects.- II. Respiratory Side Effects.- III. Central Nervous System Side Effects.- IV. Fatigue.- V. Gastrointestinal Side Effects.- VI. Genitourinary Side Effects.- VII. Glucose Metabolism.- VIII. Sensitivity Reactions.- G. Cardioprotective Effect.- H. Future Developments.- J. Conclusion.- References.- 13 Calcium Antagonists With 12 Figures.- A. Introduction.- B. Mechanism of Action of Calcium Antagonists.- C. Nifedipine.- I. Chemistry and Pharmacokinetics.- II. Pharmacodynamics in Humans.- III. Clinical Experience.- D. Diltiazem.- II. Chemistry and Pharmacokinetics.- II. Pharmacodynamics in Humans.- III. Clinical Experience.- E. Verapamil.- I. Chemistry and Pharmacokinetics.- II. Pharmacodynamics.- III. Clinical Experience.- F. Summary.- References and Additional Reading.

U Abshagen

U Abshagen

[Book]

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