PHARMACOTHERAPY OF ASCITES ASSOCIATED WITH CIRRHOSIS

Cirrhotic patients frequently develop ascites during the course of their disease. The appearance of ascites is the final consequence of profound disturbances in systemic and splanchnic haemo-dynamics, and in renal and hormonal function. The alterations in renal function consist of a decreased ability to excrete sodium and water, and in more severe cases, a reduction in renal blood flow and glomerular filtration rate. No effective drug therapy is yet available for water retention and renal failure in these patients. Sodium retention, however, may be treated by the administration of diuretics. The diuretics most commonly used in the treatment of cirrhotic patients with ascites are loop diuretics, particularly furosemide (frusemide), and distal, or 'potassium-sparing' diuretics such as spironolactone. Although furosemide has a much greater natriuretic potency than spironolactone in healthy individuals, studies in cirrhotic patients with ascites have shown that spironolactone is more effective than furosemide in the elimination of ascites. Nowadays, however, therapeutic paracentesis associated with plasma expanders has replaced diuretic therapy as the initial treatment for cirrhotic patients hospitalised with tense ascites since it is more effective and is associated with a lower rate of complications than diuretic therapy. Diuretics should be given after the elimination of ascites by paracentesis to avoid the reaccumulation of the abdominal fluid. Only cirrhotic patients with mild ascites should be treated initially with diuretics. Cirrhotic patients with ascites frequently develop a spontaneous infection of the ascitic fluid which is usually caused by Gram-negative bacilli from enteric origin and has a great tendency to recur after therapy. The antibiotics of choice for this infection are third-generation cephalosporins. Long term administration of norfloxacin, which causes a selective elimination of Gram-negative bacilli from the intestinal flora, is effective in preventing the recurrence of ascites infection in these patients. Finally, cirrhotic patients with ascites are prone to develop renal failure when treated with a variety of pharmacological agents, particularly aminoglycosides and nonsteroidal anti-inflammatory drugs. The administration of the latter drugs may also cause dilutional hyponatraemia and refractory ascites since they induce water retention and impair the renal response to diuretics.