Spironolactone ascites

In addition to spironolactone, ascites can be managed by paracentesis. That is the removal ( tapping ) of ascitic fluid from the peritoneal cavity under aseptic conditions. A colloid (human albumin solution (20%)) is infused (40 mL (8 g of albumin) per litre of ascites drained) intravenously during paracentesis, in order to prevent intravascular volume depletion and the onset of renal failure. Following paracentesis, ascites recurs in the majority (93%) if diuretic therapy is not reinstituted, but recurs in only 18% of patients treated with... 

Ascites. Patients with cirrhosis, especially fiver cirrhosis, very often develop ascites, ie, accumulation of fluid in the peritoneal cavity. This is the final event resulting from the hemodynamic disturbances in the systemic and splanchnic circulations that lead to sodium and water retention. When therapy with a low sodium diet fails, the dmg of choice for the treatment of ascites is furosemide, a high ceiling (loop) diuretic, or spironolactone, an aldosterone receptor antagonist/potassium-sparing diuretic. 

High-dose diuretics until loss of ascitic fluid o Spironolactone up to 400 enterally daily... 

Cirrhosis is a high aldosterone state spironolactone is a direct aldosterone antagonist and a primary treatment for ascites. 

Diuretics are often required in addition to the sodium restriction described previously. Spironolactone and jurosemide form the basis of pharmacologic therapy for ascites. Spironolactone is an aldosterone antagonist and counteracts the effects of activation of the renin-angiotensin-aldosterone system. In hepatic disease not only is aldosterone production increased, but its half-life is prolonged because it is hepatically metabolized. Spironolactone acts to conserve the potassium that would be otherwise excreted because of elevated aldosterone levels. 

The diuretic effect of spironolactone develops fully only with continuous administration for several days. Two possible explanations are (1) the conversion of spironolactone into and accumulation of the more slowly eliminated metabolite canrenone (2) an inhibition of aldosterone-stimulated protein synthesis would become noticeable only if existing proteins had become nonfunctional and needed to be replaced by de novo synthesis. A particular adverse effect results from interference with gonadal hormones, as evidenced by the development of gynecomastia (enlargement of male breast). Clinical uses include conditions of increased aldosterone secretion, e.g., liver cirrhosis with ascites. 

Diuretics, typically spironolactone, form the main therapy, combined with restricted salt intake. Sodium restriction is usually unnecessary where fluid retention is mild, and if marked limitation (less than 40 mmol per day intake) is imposed, may lead to impaired nutrition and is poorly accepted. Diuretic treatment often requires reinforcement with loop diuretics. Treatment can be maintained if urinary sodium excretion is at least 30 mmol per day. Removal of ascites through diuresis requires fluid transfer through the intravascular fluid compartment. If diuresis is too intense the intravascular fluid volume is reduced and hypotension causes hepatorenal failure to follow. The aim should be, through monitoring weight loss, to restrict fluid removal to 0.5 kg per day. In this way the risks of hyponatraemia, renal and hepatic impairment should be reduced. 

When ascites and edema become severe, diuretic therapy can be very useful. However, cirrhotic patients are often resistant to loop diuretics because of decreased secretion of the drug into the tubular fluid and because of high aldosterone levels. In contrast, cirrhotic edema is unusually responsive to spironolactone and eplerenone. The combination of loop diuretics and an aldosterone receptor antagonist may be useful in some patients. 

In 110 patients with cirrhosis, ascites, and hyponatremia in a multicenter, double-blind, randomized, placebo-con-trolled study of three fixed doses of satavaptan (5,12.5, or 25 mg/day) for 14 days plus spironolactone 100 mg/day, satavaptan was associated with improved control of ascites. Thirst was the main adverse effect (4). 

The child s subsequent course was one of gradual hepatic deterioration.At age 3 years, he was noted to have ascites (intra-abdominal fluid accumulation). This progressed slowly until the age of 6 years, when severe ascites and peripheral edema necessitated the initiation of spironolactone (a potassium-sparing diuretic). Several admissions to the hospital were required over the next 6 years for ascites with scrotal edema. Serum albumin values were persistently low, less than 2.0 g/dL. During this time, the patient also had two episodes of primary peritonitis (intraperitoneal infection) and one episode of a-streptococcal sepsis. 

Spironolactone, an aldosterone antagonist, is the drug of choice since secondary hyperaldosteronism often coexists in patients with hepatic ascites. Aldosterone is usually metabolised by the liver and is highly protein bound, therefore the free aldosterone levels are raised in cirrhosis. Spironolactone competes with aldosterone for receptor sites in the distal tubule, resulting in potassium retention and sodium and water loss. The initial dose of spironolactone is 100-200 mg and can be slowly increased according to response. There is a lag of 3-5 days between the beginning of spironolactone treatment and the onset of the natriuretic effect. 

Metoclopramide has been shown to significantly reduce spironolactone-induced diuresis in cirrhotic patients with ascites. When administered to patients with secondary hyperaldosteronism, metoclopramide significantly reduced urinary sodium excretion, with a corresponding increase in urinary potassium excretion and a significant increase in plasma aldosterone. This effect was not seen with domperidone. From this study it is recommended that metoclopramide is avoided during diuretic therapy in cirrhotic patients with ascites [15]. 

D Arienzo A, Ambrogio G, Di Siervi P, et al. (1985) A randomised comparison of metoclopramide and domperidone on plasma aldosterone concentration and on spironolactone-induced diuresis in ascitic cirrhotic patients. Hepatology 5 854-857. 

Both drugs are gastric irritants and should probably be avoided in patients with varices or a history of variceal bleeding or coagulopathy, or a risk thereof. Niacin can also cause thrombocytopenia. This patient has a varix and would be at risk of a variceal bleed if decompensation occurred. Niacin and acipimox also commonly cause pruritus. They are also vasodilators and may potentiate the effect of drugs that lower blood pressure (spironolactone, propranolol, furosemide), which are used to treat ascites and portal hypertension. 

The findings and observations described in the literature as well as the convincing efficacy of the aldosterone antagonist spironolactone confirm the importance of the RAAS in the genesis of renal sodium retention and hence also in the formation of ascites. 

Xipamide is classed as a low-ceiling diuretic with its effective dynamics and intensity ranking between furo-semide and the thiazides. For this reason, there are no extreme peaks of diuresis during prolonged therapy. Calciuria is typical for loop diuretics. With portal ascites, xipamide has proved to be almost diuretically equivalent to spironolactone. 

A dosage of 20 to 40 mg xipamide per day is recommended in 1-2 (-3) single doses. For long-term therapy, it is advisable to prescribe 10 mg. Diuresis sets in after about 1 hour with a peak after 2 to 8 hours. There is no rebound effect. The excretion of sodium and chloride is increased to an almost identical degree calciuria, magnesiuresis and kaliuresis occur. For this reason, xipamide should be combined with spironolactone. Biotransformation of xipamide is clearly limited in cirrhotic patients, the half-life (7 hours) is not influenced. Xipamide passes into the ascitic fluid and reaches concentrations of 10-20% of the respective plasma level. It can even be used with restricted renal function, since it has no influence on renal haemodynamics. 

Campra, J.L., Reynolds, T.B. Effectiveness of high-dose spironolactone therapy in patients with chronic liver disease and relatively refractory ascites. Dig. Dis. Sci. 1978 23 1025-1030... 

Fuller, R.K., Khambatta, P.B., Gobezie, G.C. An optimal diuretic regimen for cirrhotic ascites. A controlled trial evaluating safety and efficacy of spironolactone and furosemide. J. Amer. Med. Ass. 1977 237 972-975... 

C. A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients. Hepatology 1991 14 231-236... 

Rerez-Ayuso, RM., Arroyo, V, Rlanas, R., Gaya, J., Bory, F., Rimola, A., Rivera, F., Rodes, X Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites. Relationship between the diuretic response and the activity of the renin-aldosterone system. Gastroenterology 1983 84 961 -968... 

Santos, J., Planas, R., Pardo, A., Durandez, R., Cabre, E., Morillas, R.M., Granada, MX., Jimene J.A., Quintero, E., Gassull, M.A. Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety. J. Hepatol. 2003 39 187-192... 

Attenuation by spironolactone of the magnesiuric effect of acute furosemide administration in patients with liver cirrhosis and ascites. Miner. Electrol. Metabol. 1993 19 86-90... 

Spironolactone has been used as a potassium-sparing diuretic in cardiac failure and in the management of ascites and edema associated with hepatic cirrhosis with secondary hyperaldosteronism. It is also used to treat hyperaldosteronism due to adrenal tumors or adrenal hyperplasia. It has a weak positive inotropic effect and a modest antihypertensive effect, in keeping with its natriuretic action. 

Central nervous system effects, such as weakness, drowsiness, and confusion, have been reported in patients taking spironolactone. Because most patients with such adverse effects were taking spironolactone for edema and ascites in hepatic cirrhosis, it is not yet clear whether they were caused by the drug itself or by hepatic encephalopathy. The incidence of these complaints in such patients is quite high (9.8%) (SED-9, 357). 

Rado JP, Marosi J, Szende L, Tako J. Hyperkalemic changes during spironolactone therapy for cirrhosis and ascites, with special reference to hyperkalemic intermittent paralysis. J Am Geriatr Soc 1968 16(8) 874-86. 

Triamterene blocks dihydrofolate reductase and can cause folate deficiency with megaloblastic anemia and pancytopenia, particularly in patients with hepatic cirrhosis, who have reduced clearance of the drug (SED-11, 431). When this has been reported, all patients were taking doses of 150-600 mg/day for ascites and all had hepatic cirrhosis, often due to alcohol abuse (SEDA-17, 269). It is advisable to use spironolactone rather than triamterene in patients with cirrhosis. 

Spironolactone may be used alone us an extremely mild diuretic to remove edema fluid in individuals with congestive heart faiiure. cirrhosis of the liver with ascites, or the nc-fHmitic syndrome or as an antihypertensive agent. Its primary use, however, has been in combination with diuretics that act at site 2 or. 1 in an attempt to reduce the urinary K hiis associated with these latter groups of diuretics. 

The combination of spironolactone and furosemide is now the recommended initial diuretic therapy for patients with ascites. 

The AASLD practice guidelines recommend that diuretic therapy be initiated with the combination of spironolactone and furosemide. Spironolactone alone was commonly recommended for initial therapy, but clinical trials have demonstrated a 14-day delay in the onset of action, as well as the development hyperkalemia when spironolactone is used alone. Administering spironolactone in single daily doses is justified based on its pharmacokinetics and helps to improve patient compliance. If tense ascites is present, paracentesis... 

Adult patients admitted to the hospital with new-onset ascites should have an abdominal paracentesis performed to establish the serum-ascites albumin gradient, the ascitic fluid PMN count, and to obtain ascitic fluid cultures. Patients who drink alcohol should be strongly discouraged from further alcohol use. Sodium restriction to 2000 mg/ day, together with spironolactone and furosemide, is the main-... 

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