In search of the digitalis replacement.
There are now several new CT drugs undergoing clinical study for the treatment of CHF. While most of these new agents are like digitalis in that they possess significant inotropic activity, they differ from digitalis in that they tend to also have pronounced vasodilator properties. Such compounds, because they are not pure CT agents, should not be regarded as true digitalis replacements. Despite the increased understanding about the cAMP cascade and about cardiac muscle contraction in general, the long search for a specific digitalis replacement cannot be regarded as having been accomplished. It should also be noted that the initial clinical assessment for any of these new compounds will be complicated by the fact that they are tested in only the latter stages of CHF where prognosis is very poor and the possibility of showing significant improvement in mortality is extremely difficult. It will be unfortunate if the potential for positive inotropic agents (pure CT drugs) is compromised by clinical studies that employ mixed inotropic-vasodilator compounds in extremely sick patient populations. The continued use of the digitalis glycosides for such a long period of history implies that at least some subpopulation of CHF patients should derive benefit from therapy with an appropriately selective CT drug. Neither the appropriate drug nor the appropriate specific patient population, both of which are needed to properly address the eventual role of inotropic therapy in CHF, have, as yet, been identified.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology; D004071:Digitalis Glycosides / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D009200:Myocardial Contraction; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D004071:Digitalis Glycosides; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases