Interest of the association clonidine-spironolactone in cirrhotic patients with ascites and activation of sympathetic nervous system

• Published in: Acta gastro-enterologica belgica Vol. 65; no. 1; p. 1
• Main Authors: Lenaerts, A, Codden, Th, Van Cauter, J, Meunier, J C, Henry, J P, Ligny, G
• Format: Journal Article
• Language: English
• Published: Belgium 01.01.2002
• Subjects: Adrenergic alpha-Agonists - administration & dosage; Adrenergic alpha-Agonists - therapeutic use; Clonidine - administration & dosage; Clonidine - therapeutic use; Diuretics - administration & dosage; Diuretics - therapeutic use; Drug Therapy, Combination; Female; Hemodynamics - drug effects; Humans; Liver Cirrhosis, Alcoholic - drug therapy; Liver Cirrhosis, Alcoholic - physiopathology; Male; Middle Aged; Natriuresis - drug effects; Renin-Angiotensin System - drug effects; Spironolactone - administration & dosage; Spironolactone - therapeutic use; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Weight Loss
• ISSN: 1784-3227

The aim of this study was to examine the effects of spironolactone, clonidine and the association of clonidine-spironolactone on renin-aldosterone and sympathetic systems, renal function, systemic hemodynamics and mobilization of ascites in 32 alcoholic cirrhotic patients with marked increase in sympathetic system. Measurements were taken before and after an 8-day treatment with spironolactone (200 mg/day), after an 8-day treatment with clonidine (0.150 mg/day) and 10 days after adjunction of spironolactone (200 mg/day) to clonidine. Three patients abandoned the treatment or were excluded because lack of compliance. Spironolactone alone induced an increase in renin-aldosterone and sympathetic systems without any remarkable increase of natriuresis and body weight loss. Given for 8 days, clonidine alone induced a significant decrease in plasma norepinephrine associated with a significant increase in glomerular filtration rate without effect on natriuresis. In contrast, 10 days after adjunction of spironolactone to clonidine, plasma renin and aldosterone significantly decreased, natriuresis increased (from 7.4 +/- 0.7 to 41.6 +/- 3.2 mEq/24 h) and body weight decreased (from 66.03 +/- 2.3 to 63.5 +/- 2.3 kg) without adverse effects. In cirrhotic patients with ascites and marked activation of sympathetic nervous system, spironolactone (200 mg/day) is unable to mobilize ascites. In these patients, after 8 days, clonidine decreases sympathetic activity, increases glomerular filtration rate and after 18 days, decreases plasma renin and aldosterone concentrations allowing a better action of spironolactone. The association clonidine-spironolactone enhances natriuresis and body weight loss.