Pharmacology of new agents for acute heart failure syndromes.
Current therapies for acute heart failure syndromes (AHFS) target hemodynamics by decreasing congestion or increasing myocardial contraction. Several new agents for AHFS use novel mechanisms of action that focus on new treatment targets, such as those providing anti-ischemic and anti-stunning effects, blocking vasopressin receptors, or blocking endothelin-1 receptors. For example, levosimendan acts as a calcium sensitizer and adenosine triphosphate-dependent potassium (K(ATP)) channel opener that increases contraction, causes vasodilation, and provides cardioprotective effects. This is accomplished by its dual mechanism of action. Levosimendan binds to cardiac troponin C, thereby enhancing calcium myofilament responsiveness and increasing myocardial contraction without increasing intracellular calcium levels. Thus, contraction is increased with no significant increase in myocardial oxygen consumption. The opening of K(ATP) channels by levosimendan causes vasodilation and exerts anti-ischemic and anti-stunning effects on the myocardium. Other new agents target neurohormonal pathways. Tezosentan is an antagonist of endothelin-1 receptors A and B. By inhibiting endothelin-1 receptors, tezosentan may counteract the activities of endothelin-1, which include vasoconstriction, proarrhythmic activities, potentiation of other neurohormones, and mediation of increased vascular permeability. Tolvaptan is a vasopressin V2-receptor antagonist that functions as an aquaretic (ie, it increases urine volume and serum sodium with little or no sodium loss). Therefore, by using novel mechanisms of action, these agents may provide new opportunities for helping patients with AHFS.
Gheorghiade
Mihai
M
Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. m-gheorghiade@northwestern.edu
Teerlink
John R
JR
Mebazaa
Alexandre
A
D000208:Acute Disease; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D065128:Endothelin Receptor Antagonists; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use; D011724:Pyridazines / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D000077464:Simendan; D013577:Syndrome; D013777:Tetrazoles / Q000627:therapeutic use; D000077602:Tolvaptan; D014665:Vasodilator Agents / Q000627:therapeutic use
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D002316:Cardiotonic Agents; D065128:Endothelin Receptor Antagonists; D006835:Hydrazones; D011724:Pyridazines; D011725:Pyridines; D013777:Tetrazoles; D014665:Vasodilator Agents; D000077602:Tolvaptan; D000077464:Simendan; C120582:tezosentan