[The process of drug development. The "case" of spironolactone].
In the progressive understanding of the heart failure syndrome different models have followed. Current pathophysiology model suggests that heart failure is a neurohormonal disorder: an abnormality in cardiac function and a disturbance in myocardial contractile force is the initiating event in heart failure, and the clinical expression and progression of the disease occurs as a result of subsequent extracardiac alterations. Treatment with drugs capable of antagonizing the effects of neuroendocrine activation, such as angiotensin-converting enzyme inhibitors, beta-blockers and antialdosterone agents have induced a significant reduction in morbidity and mortality in heart failure patients. The progressive understanding of the circulating homeostasis mechanisms moved from the systemic to the paracrine aspects of the neurohormonal systems and contributed to the development of new drugs. Moreover, the analysis of a drug's development can be an important step in the medical knowledge advancement. In this sense, aldosterone and spironolactone became an interesting "case", which is analyzed in this paper, going through the steps that have promoted the spironolactone from a weak diuretic to a neurohormonal drug and, finally, to a "central" drug.
De Feo
Stefania
S
Divisione di Cardiologia, Fondazione S. Maugeri, Clinica del Lavoro e della Riabilitazione, IRCCS, Istituto Scientifico, Pavia.
Opasich
Cristina
C
Volpi
Alberto
A
Tavazzi
Luigi
L
D000818:Animals; D005355:Fibrosis / Q000517:prevention & control; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013148:Spironolactone / Q000627:therapeutic use*
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone
Considerazioni sul percorso di sviluppo di un farmaco. Il "caso" dello spironolattone.