Congestive heart failure drugs, specific agents

Edema and specific drugs for its treatment have long been problems of the physician and of the chemist interested in medicinal products. Digitalis and the many related cardiac glycosides were the first effective agents for the treatment of dropsy associated with congestive heart failure. However, it was soon recognized that the mobilization of the excess tissue fluid associated with this condition was due to a primary action on the heart with improved cardiovascular hemodynamics and only secondarily to an action upon the kidney. 

Inhibitors of a heart-specific subtype (type III) phosphodiesterase, which are positive inotropics, may be used in the short-term treatment of severe congestive cardiac failure, e.g. amrinone, enoximone and milrinone. However, developments of oral formulations of drugs of this type have been halted by the results of the PROMISE trial (Prospective Randomised Milrinone Survival Evaluation trial) which documented a paradoxical increase in mortality in class IV heart failure patients randomised to receive milrinone. However, some benzimidazole derivatives with class III phosphodiesterase inhibitor actions seem to be beneficial in heart failure. The agent vesnarinone is an orally active compound that may act as a class III phosphodiesterase inhibitor but appears to be a vasodilator with multiple mechanisms. See HEART FAUURE TREATMENT INOTROPIC AGENTS. 

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