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The most successful therapeutic regimen is the combination of single morning oral doses of spironolactone and furosemide, beginning with 100 mg and 40 mg, respectively [23] . This combination in this ratio usually maintains normokalemia. At least one controlled trial (reported as an abstract) demonstrated that treatment with both diuretics can mobilize moderate ascites more rapidly than sequential diuretics (ie, spironolactone alone followed by adding furosemide) [24] .
The doses can be doubled if a clinical response is not evident. The maximum recommended doses are spironolactone 400 mg/day and furosemide 160 mg/day [1,3] . The long half-life of spironolactone makes single-daily dosing most appropriate. Giving both drugs once per day in the morning maximizes compliance and minimizes nocturia. (See "Optimal dosage and side effects of loop diuretics").
Interestingly, spironolactone, an aldosterone antagonist is more effective than furosemide alone in patients with cirrhosis [23,25] . The surprising finding that a normally weak diuretic may be more effective than a loop diuretic in cirrhotic ascites may be related to differences in the mechanism of drug action [25] . Most loop and thiazide diuretics are highly protein-bound; as a result, they enter the tubular lumen by secretion in the proximal tubule, not by glomerular filtration. This secretory process appears to be impaired in cirrhosis, perhaps due to competitive or toxic inhibition by retained compounds such as bile salts. The net effect is that diuretic entry into the lumen and therefore the natriuretic effect may be limited [26] .
Single-agent spironolactone regularly causes hyperkalemia in patients with cirrhosis and ascites. The concomitant use of furosemide usually leads to better urine sodium excretion as well as normokalemia. This combination has stood the test of time and is probably the most common treatment for patients with cirrhosis and ascites. The only setting in which we begin with spironolactone monotherapy is in patients with severe alcoholic hepatitis who have profound hypokalemia. Furosemide is added once the potassium normalizes.
Spironolactone is occasionally associated with painful gynecomastia. As a result, amiloride, another potassium-sparing diuretic that directly closes the aldosterone-sensitive luminal sodium channels in the collecting tubules, has also been used in the treatment of ascites. However, amiloride appears be less effective than spironolactone in cirrhotic patients.
Tumorigenic: [U.S. Boxed Warning]: Shown to be a tumorigen in chronic toxicity animal studies.
РЛС - Сообщалось о случаях рака молочной железы у мужчин и женщин, получавших спиронолактон, однако причинно-следственная связь не установлена.
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