Calcium Antagonists

1 Physiological Significance of Calcium: Calcium Antagonism.- 1.1 Physiological Significance of Calcium.- 1.1.1 Action Potential and Cardiac Pacemaker Cells.- 1.1.2 Excitation-Contraction Coupling in the Myocardium.- 1.1.2.1 Action Potential in the Myocardial Cell.- 1.1.2.2 Anatomy of the Myocardial Cell.- 1.1.2.3 Cellular and Subcellular Calcium Movements.- 1.1.2.4 Molecular Mechanism of Muscle Contraction.- 1.1.3 Excitation-Contraction Coupling in Smooth Muscle.- 1.2 Calcium Antagonism.- 1.2.1 Definition of Calcium Antagonists.- 1.2.2 Basic Effects on the Heart.- 1.2.3 Basic Effects on Smooth Muscle.- 1.2.4 Mechanism and Site of Action.- 1.2.5 Classification of Calcium Antagonists.- References.- 2 Chemical Structure and Pharmacokinetics of Calcium Antagonists.- 2.1 Chemical Structure.- 2.1.1 Verapamil Group.- 2.1.2 Diltiazem.- 2.1.3 Dihydropyridine Group.- 2.1.4 Other Calcium Antagonists.- 2.2 Pharmacokinetics.- 2.2.1 Verapamil Group.- 2.2.2 Diltiazem.- 2.2.3 Dihydropyridine Group.- 2.2.4 Other Calcium Antagonists.- 2.2.5 Dosage Guidelines for Galium Antagonists: Individualized Dosage.- 2.2.6 Generics: Sustained-Release Preparations.- References.- 3 Pharmacological Effects of Calcium Antagonists.- 3.1 Cardiovascular System.- 3.1.1 Preliminary Remarks.- 3.1.2 Pacemaker and Conduction System.- 3.1.3 Myocardium.- 3.1.4 Cardioprotection.- 3.1.5 Vascular System.- 3.1.5.1 Coronary Vessels.- 3.1.5.2 Other Vessels.- 3.1.6 Integrated Haemodynamic Response.- References.- 3.2 Smooth Muscle.- 3.2.1 Gastrointestinal Tract.- 3.2.2 Respiratory Tract.- 3.2.3 Urogenital Tract.- References.- 3.3 Other Organ Systems.- 3.3.1 Kidney.- 3.3.2 Metabolism - Endocrinology.- 3.3.3 Erythrocytes - Thrombocytes - Mast Cells.- 3.3.4 Eye.- 3.3.5 Bone-Mineral Metabolism.- 3.3.6 Central Nervous System.- References.- 3.4 Atherosclerosis - Antiatherogenic Effects.- References.- 4 Indications for Calcium Antagonists.- 4.1 Coronary Heart Disease.- 4.1.1 Presenting Forms: Coronary Physiology.- 4.1.2 Stable Angina Pectoris.- 4.1.2.1 Monotherapy with Calcium Antagonists.- 4.1.2.2 Mechanism of Action.- 4.1.2.3 Combination Therapy with Calcium Antagonists.- 4.1.2.4 Practical Considerations.- References.- 4.1.3 Unstable Angina Pectoris.- 4.1.3.1 Prinzmetal's Angina Pectoris.- 4.1.3.2 Syndrome X.- References.- 4.1.4 Myocardial Infarction (MI).- 4.1.4.1 Primary Prevention of MI.- 4.1.4.2 Calcium Antagonists in the Acute Phase of MI.- 4.1.4.3 Long-Term Therapy with Calcium Antagonists Following Acute MI (Secondary Prevention).- References.- 4.1.5 Arrhythmias in Coronary Heart Disease.- References.- 4.1.6 Silent Myocardial Ischaemia - Therapy with Calcium Antagonists.- References.- 4.2 Hypertension.- 4.2.1 Fundamentals of Antihypertensive Therapy with Calcium Antagonists.- 4.2.1.1 Definition.- 4.2.1.2 Hypertension as a Risk Factor or Risk Indicator.- 4.2.1.3 Stepped Care Versus Individualized Therapy.- 4.2.1.4 Discovery of the Antihypertensive Action of Calcium Antagonists.- References.- 4.2.2 Mechanism of Antihypertensive Action of Calcium Antagonists.- References.- 4.2.3 Monotherapy with Calcium Antagonists in Hypertension 123 References.- 4.2.4 Calcium Antagonists in Antihypertensive Combination Therapy (with Inclusion of Special Treatment Criteria).- 4.2.4.1 Combination with ?-Receptor Blockers.- 4.2.4.2 Combination with Diuretics.- 4.2.4.3 Combination with Other Antihypertensives.- 4.2.4.4 Special Treatment Criteria and Marginal Indications 132 References.- 4.2.5 Calcium Antagonists in Hypertensive Emergencies 134 References.- 4.3 Cardiac Arrhythmias.- 4.3.1 Mechanism of Antiarrhythmic Action of Calcium Antagonists.- 4.3.1.1 Mechanism of Action in Supraventricular Arrhythmias.- 4.3.1.2 Mechanisms of Action in Ventricular Arrhythmias.- 4.3.2 Supraventricular Arrhythmias.- 4.3.2.1 Sinus Tachycardia.- 4.3.2.2 Paroxysmal Supraventricular Tachycardia.- 4.3.2.3 Atrial Fibrillation.- 4.3.2.4 Atrial Flutter.- 4.3.2.5 Supraventricular Extrasystoles.- 4.3.3 Wolff-Parkinson-White Syndrome.- 4.3.4 Ventricular Arrhythmias.- 4.3.5 Digitalis-Induced Arrhythmias.- 4.3.6 Drug Interactions in Antiarrhythmic Combination Therapy.- References.- 4.4 Cardiomyopathies.- 4.4.1 Pathophysiological Classification of Cardiomyopathies According to Haemodynamic Criteria.- 4.4.2 Haemodynamics and Diagnosis of Hypertrophic Cardiomyopathy.- 4.4.3 Therapy of Hypertrophic Cardiomyopathy with Calcium Antagonists.- 4.4.4 Haemodynamics and Diagnosis of Dilated Cardiomyopathy.- 4.4.5 Treatment of Dilated Cardiomyopathy with Calcium Antagonists.- References.- 4.5 Other Cardiac Indications.- 4.5.1 Congestive Heart Failure.- 4.5.1.1 Fundamentals of Therapy with Vasodilators.- 4.5.1.2 Therapy of Congestive Heart Failure with Calcium Antagonists.- 4.5.2 Aortic Regurgitation.- 4.5.3 Application of Calcium Antagonists in Heart Surgery.- 4.5.4 Calcium Antagonists in Coronary Arteriography and Percutaneous Transluminal Coronary Angioplasty.- 4.5.5 Cardiac Involvement in Systemic Sclerosis: Hyperkinetic Heart Syndrome: Cardioprotection in Tocolysis.- References.- 4.6 Other Vascular Indications.- 4.6.1 Pulmonary Hypertension.- 4.6.2 Raynaud's Syndrome.- 4.6.3 Ergotism: Mesenteric Ischaemia: Arterial Occlusive Disease: Chronic Venous Insufficiency: Accidental Intraarterial Injection of Drugs.- 4.6.4 Atherosclerosis.- References.- 4.7 Calcium Antagonists in Neurological Disease (Claudia Trenkwalder).- 4.7.1 Migraine.- 4.7.1.1 Classification and Definition.- 4.7.1.2 Pathogenetic Factors.- 4.7.1.3 Mechanism of Action of Calcium Antagonists: Experimental Studies in Animals.- 4.7.1.4 Prophylactic Treatment of Migraine: Clinical Studies.- 4.7.1.5 Prophylactic Treatment in Childhood.- References.- 4.7.2 Vasospasm Following Subarachnoid Haemorrhage.- 4.7.2.1 Pathogenesis and Experimental Studies.- 4.7.2.2 Clinical Studies and Therapy of Vasospasm.- References.- 4.7.3 Calcium Antagonists in Cerebral Ischaemia and in Cardiopulmonary Resuscitation.- 4.7.3.1 Pathophysiology and Animal Studies.- 4.7.3.2 Clinical Studies.- References.- 4.7.4 Vertigo.- References.- 4.7.5 Epilepsy.- 4.7.5.1 Mechanism of Action of Flunarizine.- 4.7.5.2 Clinical Studies.- References.- 4.7.6 Further Indications.- References.- 4.8 Gastrointestinal Tract.- 4.8.1 Oesophagus.- 4.8.2 Small Intestine: Large Intestine.- 4.8.3 Gallbladder: Bile Ducts.- 4.8.4 Other Gastrointestinal Indications.- References.- 4.9 Respiratory Tract.- 4.9.1 Asthma.- 4.9.2 Chronic Obstructive Pulmonary Disease.- References.- 4.10 Urogenital Tract.- 4.10.1 Ureteral Spasm: Ureteral Colic: Renal Colic.- 4.10.2 Detrusor Instability (Detrusor Hyperreflexia - Irritable Bladder - Nervous Bladder).- 4.10.3 Tocolysis.- 4.10.3.1 Direct Tocolytic Action of Calcium Antagonists.- 4.10.3.2 Application of Calcium Antagonists for Cardioprotection in Tocolysis with ?-Sympathomimetics.- 4.10.4 Dysmenorrhoea.- References.- 4.11 Further Indications for Calcium Antagonists.- References.- 4.12 Calcium Antagonists in Anaesthesiology.- References.- 5 Side Effects - Overdosage - Contraindications - Drug Interactions.- 5.1 Side Effects Directly due to Blockade of Calcium-Dependent Metabolic Processes.- 5.2 Side Effects Independent of Blockade of Calcium-Dependent Metabolic Processes.- 5.3 Substance-Specific Side Effects.- 5.4 Overdosage of Calcium Antagonists: Intoxication.- 5.5 Incidence of Side Effects.- 5.6 Contraindications.- 5.7 Withdrawal of Calcium Antagonists: A Calcium Antagonists Withdrawal Syndrome?.- 5.8 Drug Interactions in Calcium Antagonist Therapy 232 References.- 6 Perspective: What Next?.- References.