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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lenaerts
A
A
Department of Hepato-Gastroenterology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium. bs301272@skynet.be
Codden
Th
T
Van Cauter
J
J
Meunier
J C
JC
Henry
J P
JP
Ligny
G
G
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D003000:Clonidine / Q000008:administration & dosage / Q000627:therapeutic use*; D004232:Diuretics / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D013148:Spironolactone / Q000008:administration & dosage / Q000627:therapeutic use*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D015431:Weight Loss
D000316:Adrenergic alpha-Agonists; D004232:Diuretics; D013148:Spironolactone; D003000:Clonidine