Diuretics
Overview
Diuretics are commonly used to treat pulmonary arterial hypertension patients with right-ventricular failure (e.g., those suffering from peripheral edema and/or ascites). The ACCP guidelines emphasize that the long-term management of pulmonary arterial hypertension patients requires the maintenance of near-normal intravascular volume via the use of diuretics in addition to reduced dietary salt intake. However, the guidelines also stress that rapid and excessive diuresis may exacerbate patient symptoms, leading to systemic hypotension, renal problems, and syncope. As a result, patients receiving diuretic therapy should be carefully monitored.
The choice of diuretic is tailored to suit the individual, taking into account the severity of the disease and any potential contraindications. If only mild diuresis is required or the physician has concerns about electrolytes, a potassium-sparing diuretic such as spironolactone (Pfizer’s Aldactone, generics) is the agent of choice. If a greater diuretic effect is needed, loop diuretics such as furosemide (Sanofi-Aventis’s Lasix, generics) and torsemide (Roche’s Demadex, generics) are recommended. If a thiazide is needed, hydrochlorothiazide (Merck’s Hydrodiuril, Novarris’s Esidrex, generics) is the agent of choice.
Mechanism Of Action
All diuretics increase the excretion of sodium and water, thereby reducing plasma volume, cardiac output, and peripheral resistance. Thiazide diuretics increase sodium and water excretion via inhibition of the sodium/chloride cotransporter in the distal convoluted tubule of the kidney nephron. Loop diuretics are more potent than thiazides, causing up to 15-20% of filtered sodium to be excreted. These agents act on the sodium-potassium-2-chloride cotransporter located in the ascending loop of Henle. Potassium-sparing diuretics are generally weak diuretics that act on aldosterone-sensitive sites in the nephron; they are associated with fewer side effects than the other subclasses.
Furosemide
First approved by the FDA in 1968 for the treatment of systemic hypertension, furosemide (Sanofi-Aventis’s Lasix, generics) is a popular treatment option for reducing fluid volume in pulmonary arterial hypertension patients. It is available in Europe and Japan as well. Furosemide is a loop diuretic that exerts its effects on sodium and chloride reabsorption in the proximal and distal tubules and in the ascending loop of Henle. The diuretic effects of furosemide therapy are observed after one hour and last six to eight hours. Because furosemide is a highly potent agent, patients must be monitored for side effects, such as systemic hypotension and syncope, although these problems are generally experienced at high doses — 180mg per day or more. Clinical trials assessing the benefits of furosemide in the treatment of pulmonary arterial hypertension are not available.
Spironolactone
Spironolactone (Pfizer’s Aldactone, generics) has been available in the United States since 1982. The potassium-sparing diuretic promotes diuresis via inhibition of mineralocorticoid receptors. Spironolactone is used to treat pulmonary arterial hypertension when other diuretic agents are inappropriate or not sufficient (i.e., it may be used in combination with other diuretic agents). Spironolactone is often a popular choice in the presence of ascites. The agent may have unwanted side effects, including gynecomastia due to the agent’s activity on androgen receptors, and hyperkalemia, which may lead to cardiac abnormalities. The presence of such side effects may require that treatment be discontinued. No clinical studies have evaluated spironolactone in the treatment of pulmonary arterial hypertension.
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