Calcium Antagonists

Our research at the Freiburg Physiological Institute over the past 25 years has demonstrated that specific calcium antagonists interfere with all physiological and pathophysiological reactions involving the heart and vessels in which an elevated inflow of calcium ions across the potential-dependent slow membrane channels into the cells is a decisive factor. From the outset, our therapeutic interest has centred on the possibility of inhibiting excessively high levels of transmembrane cal cium influx and thereby reducing the pathogenic consequences of intra cellular calcium overload. For example, all excessive calcium influx evokes contractile hyperactivity, which manifests itself in the myocardial fibres as hyperkinetic reactions and an uneconomic rise in oxygen de mand and, analogously, in vascular smooth muscle cells as increased tonus and spasm. The therapeutic use of calcium antagonists to inhibit excessive mechanical and metabolic activity in the myocardium and to achieve prophylaxis and lysis in smooth muscle spasm was therefore a logical step. The highest potencies of calcium antagonists were found in the vas cular smooth musculature (coronary, cerebral, mesenteric and renal arteries and other systemic resistance vessels). Consequently, calcium antagonists were recognized as the agents of choice for numerous indica tions for vascular therapy. It is well established that calcium ions are also essential for the generation of impulses in cardiac pacemaker cells and for the conduc tion of electrical charges.

1 Physiological Significance of Calcium: Calcium Antagonism. - 1. 1 Physiological Significance of Calcium. - 1. 2 Calcium Antagonism. - References. - 2 Chemical Structure and Pharmacokinetics of Calcium Antagonists. - 2. 1 Chemical Structure. - 2. 2 Pharmacokinetics. - References. - 3 Pharmacological Effects of Calcium Antagonists. - 3. 1 Cardiovascular System. - References. - 3. 2 Smooth Muscle. - References. - 3. 3 Other Organ Systems. - References. - 3. 4 Atherosclerosis Antiatherogenic Effects. - References. - 4 Indications for Calcium Antagonists. - 4. 1 Coronary Heart Disease. - References. - References. - References. - References. - References. - 4. 2 Hypertension. - References. - References. - 4. 3 Cardiac Arrhythmias. - References. - 4. 4 Cardiomyopathies. - References. - 4. 5 Other Cardiac Indications. - References. - 4. 6 Other Vascular Indications. - References. - 4. 7 Calcium Antagonists in Neurological Disease (Claudia Trenkwalder). - References. - References. - References. - References. - References. - References. - 4. 8 Gastrointestinal Tract. - References. - 4. 9 Respiratory Tract. - References. - 4. 10 Urogenital Tract. - 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: WhatNext? . - References.