Carvedilol: preclinical profile and mechanisms of action in preventing the progression of congestive heart failure.
Many pathophysiological processes are activated in patients with congestive heart failure, and several of these have been implicated in the progression of the disease. The most important processes to be activated in heart failure are the neurohormonal systems, which include the reninangiotensin system, the sympathetic nervous system and the endothelin system. In addition to the neurohormonal systems, the formation of reactive oxygen free radicals is increased in congestive heart failure. It has been proposed that the activation of neurohormonal pathways and the formation of oxygen free radicals ultimately lead to the activation of a family of transcription factors that are involved in cardiac and vascular remodelling which are hallmarks of congestive heart failure. In addition, the formation of oxygen free radicals has been implicated in the process of apoptosis, or programmed cell death, which may contribute to the continued loss of myocardial cells resulting in progressive decreases in left ventricular function, while at the same time contributing to the cardiac remodelling process which subsequently creates a pro-arrhythmic environment in the myocardium. Carvedilol is a novel multiple-action neurohormonal antagonist that has been shown to be effective in the management of congestive heart failure. Carvedilol also possesses a number of additional activities which may inhibit many of the chronic pathophysiological processes that are involved in the progression of congestive heart failure.
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Division of Pharmacological Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
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D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D018450:Disease Progression; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors; D011412:Propanolamines / Q000627:therapeutic use*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D002227:Carbazoles; D018377:Neurotransmitter Agents; D011412:Propanolamines; D000077261:Carvedilol