Cardiac Glycosides 1785-1985: Biochemistry -- Pharmacology -- Clinical Relevance

The bicentenary of William Withering's now famous medical report entitled "An Account of the Foxglove and Some of its Medical Uses" has given us the occasion to analyze the state of the art. Cardiac glycosides in 1985 are considered tobe the basis for medical treatment of myocardial failure, together with diuretics and vasodilators in the more severe cases. Nevertheless, the controversy as to their exact place in the treatment of heart failure with sinus rhythm has never ceased. Although cardiac glycosides are of unquestionable value in tachycardia caused by atrial fibrillation or atrial flutter, the chronic use of these drugs in sinus rhythm is not generally accepted. The development of tolerance has been reported. It is of interest that Withering hirnself wrote: "-let it (foxglove) be continued until it either acts on the kidneys, the stomach, the pulse, or the bowels; Iet it be stopped upon the first appearance of any of these effects, and I will maintain that the patient will not suffer from its exhibition, nor the practitioner be disappointed in any reasonable expectation. " In West Germany alone, more than three million patients (about 5% of the total population) are constantly taking cardiac glycosides. These drugs are the most prescribed medicaments in many countries. Thus, we considered it worthwhile and necessary to review in a critical way today's knowledge about the foxglove; to report new findings and to evaluate old Statements. Front Matter....Pages I-XVII William Withering — The man and his work....Pages 1-10 Fruitful routes and blind alleys taken by digitalis therapy since its introduction by Withering....Pages 11-16 Therapeutic use of digitalis until the time of William Withering....Pages 17-18 The function of Na + ,K + -ATPase and its importance for drug action....Pages 19-25 Structural studies on the cardiac glycoside receptor....Pages 27-33 Isoenzymes of Na,K-ATPase identified by pyrithiamin....Pages 35-40 Interaction of cardiac glycosides with Na/K-ATPase in intact myocardium....Pages 41-47 The human red blood cell: A model for ouabain receptor regulation in the heart?....Pages 49-54 Binding and release of ouabain at low Mg 2+ in reconstituted human red blood cell ghosts....Pages 55-59 The ouabain receptor in the myocardium and conduction system of the sheep heart....Pages 61-68 Electrophysiological effects of cardiac glycosides....Pages 69-78 Electrophysiological assay of glycoside-induced sodium pump inhibition in isolated sheep heart Purkinje fibres at the onset of toxicity....Pages 79-86 Rat cardiac hypertrophy: contribution of heteregeneous digitalis receptor forms....Pages 87-92 Digitalis receptors in normal and hypertrophied rat hearts. Differential effects of a Ca 2+ free perfusion....Pages 93-98 Biphasic contractile response to ouabain: Species specific? Calcium dependent? Altered sensitivity?....Pages 99-108 The influence of α -tocopherol-nicotinate (Renascin ® ) on cardiac glycoside effects....Pages 109-117 On the connection between cardiac glycosides and calcium action....Pages 119-125 Biochemical basis for the targeted synthesis of cardiac glycosides with selective action....Pages 127-134 The “endogenous cardiac glycoside”....Pages 135-142 Endogenous digitalis, cardiodigin and other regulators of the sodium pump....Pages 143-155 Digitalis-like factors in plasma of healthy human adults....Pages 157-164 A Na + ,K + -ATPase inhibitor isolated from pig kidney....Pages 165-169 Cardiac glycoside-like effects of a bufadienolide extracted from Kalanchoe Daigremontiana....Pages 171-179 Positive inotropic agents: Different mechanisms of action....Pages 181-188 Significance of calcium ions in the regulation of myocardial contractility....Pages 189-194 Additive and non-additive positive inotropic effects in human and guinea-pig myocardium....Pages 195-205 The cardiac Na + /H + exchange system. Its role in inotropy....Pages 207-213 Evidence for pharmacodynamic differences between cardiac glycosides of different polarities....Pages 215-219 The positive inotropic action of mercury compounds on isolated heart muscle....Pages 221-227 Chronic pretreatment with amrinone or milrinone induces no tachyphylaxis in mammalian cardiac muscle....Pages 229-236 Left ventricular function after oral milrinone in patients with congestive heart failure. A hemodynamic and angiographic study....Pages 237-244 The importance of skeletal muscles as a distribution volume for digitalis glycosides in guinea-pigs and human subjects....Pages 245-255 Relevant metabolism of cardiac glycosides....Pages 257-262 The dihydrogenation of digoxin....Pages 263-268 Renal excretion and plasma levels of dihydrodigitoxin in volunteers and renally healthy and renally insufficient patients being treated with digitoxin....Pages 269-272 Enzymatic basis for digitoxin metabolism and possible drug interactions in man....Pages 273-279 Effect of quinidine on the inotropic effect of digoxin in isolated cat or guinea-pig papillary muscle....Pages 281-286 Quinidine decreases the intestinal secretion of digoxin and digitoxin in the guinea-pig....Pages 287-292 Quinidine-induced reduction of the biliary excretion of digoxin in patients....Pages 293-296 Role of the bile acid transport system in hepatocellular ouabain uptake....Pages 297-304 Distribution of digoxin, digitoxin and their cardioactive metabolites in human heart and kidney....Pages 305-313 Application of HPLC-DAD instead of the guinea-pig test for the quantitative determination of cardiac glycosides....Pages 315-321 Interaction between 16-acetyl-gitoxin and drugs....Pages 323-328 Digitoxin protein binding in patients on hemodialysis....Pages 329-335 The effect of physical exercise on the distribution and renal excretion of digoxin....Pages 337-342 Ouabain binding to erythrocytes from neonates, blood cord and pregnant women....Pages 343-346 Extracardiac effects of cardiac glycosides....Pages 347-356 Effects of digitalis on renal tubular sodium reabsorption....Pages 357-365 Ouabain-induced efflux of catecholamines and metabolites from blood vessels of normotensive and hypertensive dogs....Pages 367-376 Digoxin-specific antibody treatment of digitalis toxicity: Update....Pages 377-382 Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication....Pages 383-388 Influence of tubular Na-K-ATPase activity on the development of hyperkalemia in digoxin intoxications....Pages 389-394 24-Hour Holter ECG in digoxin intoxicated patients....Pages 395-398 Clinically relevant interactions with cardiac glycosides....Pages 399-406 Importance of serum glycoside concentrations....Pages 407-416 Metabolic aspects of compensatory mechanisms in cardiac failure....Pages 417-428 Effects of digitalis glycosides on the systemic arterial and venous system: clinical importance in the pathophysiology of congestive heart failure....Pages 429-436 Attenuation of cardiac glycoside effects during long-term treatment....Pages 437-445 When to start digitalis?....Pages 447-453 Cardiotonic effect of digitalis in sinus rhythm during exercise....Pages 455-460 Digitalis treatment in pulmonary heart disease....Pages 461-469 Cardiac glycosides for paroxysmal atrial fibrillation?....Pages 471-475 Cardiac glycosides in anaesthesia....Pages 477-486 Effects of preoperative digitalisation on postoperative left heart performance and incidence of complications following hip surgery. First results of a prospective study....Pages 487-492 Digoxin therapy and mortality following confirmed or suspected myocardial infarction: Experience in the MILIS study....Pages 493-508 Improvement of ventricular function by treatment with β-methyldigoxin in patients with sinus rhythm after extended myocardial infarction: An exercise-radionuclide-ventriculography study....Pages 509-515 Effect of intravenous digoxin on left ventricular contractility at rest and during isometric exercise in intact and pharmacologically denervated heart....Pages 517-518 Low versus medium dosage digoxin therapy in patients with heart failure. A randomized, double-blind, cross-over study....Pages 519-525 The effects of digoxin and xamoterol in patients with moderate cardiac failure....Pages 527-530 The clinical, haemodynamic, and pharmacological consequences of withdrawal of digoxin after long-term treatment in patients with heart failure in sinus rhythm....Pages 531-533 New positive inotropic agents: Advantages and disadvantages....Pages 535-540 When should digitalis be discontinued?....Pages 541-548 Back Matter....Pages 549-552