Diuretics aldosterone antagonists

Mobilization of edemas (A) In edema there is swelling of tissues due to accumulation of fluid, chiefly in the extracellular (interstitial) space. When a diuretic is given, increased renal excretion of Na and H2O causes a reduction in plasma volume with hemoconcentra-tion. As a result, plasma protein concentration rises along with oncotic pressure. As the latter operates to attract water, fluid will shift from interstitium into the capillary bed. The fluid content of tissues thus falls and the edemas recede. The decrease in plasma volume and interstitial volume means a diminution of the extracellular fluid volume (EFV). Depending on the condition, use is made of thiazides, loop diuretics, aldosterone antagonists, and osmotic diuretics. 

ACE INHIBITORS, ANGIOTENSIN II RECEPTOR ANTAGONISTS POTASSIUM-SPARING DIURETICS, ALDOSTERONE ANTAGONISTS t risk of hyperkalaemia Additive retention of potassium Monitor serum potassium every week until stable, then every 3-6 months... 

POTASSIUM-SPARING DIURETICS SULPHONYLUREAS -CHLORPROPAMIDE Risk of hyponatraemia when chlorpropamide is given to a patient taking both potassiumsparing diuretics/aldosterone antagonists and thiazides Additive effect chlorpropamide enhances ADH secretion Monitor serum sodium regularly... 

UTHIUM LOOP DIURETICS, POTASSIUM-SPARING DIURETICS, ALDOSTERONE ANTAGONISTS, THIAZIDES t plasma concentrations of lithium, with risk of toxic effects L renal excretion of lithium Monitor clinically and by measuring blood lithium levels for lithium toxicity. Loop diuretics are safer than thiazides... 

Spironolactone is the most clinically usehil steroidal aldosterone antagonist, and unlike GR antagonists, this compound is utilized much more frequendy than aldosterone agonists. Interfering with reabsorption and secretion in the late distal segment, this compound is predominantiy used with other diuretics. Canrenone, an olefinic metaboHte of spironolactone, and potassium canrenoate, in which the C-17 lactone has been hydrolyzed open, are also potent mineralocorticoid antagonists. 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

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. 

Potassium-sparing diuretics are often coadministered with thiazide or loop diuretics in the treatment of edema and hypertension. In this way, edema fluid is lost to the urine while K+ ion balance is better maintained. The aldosterone antagonists are particularly useful in the treatment of primary hyperaldosteronism. 

The answer is c. (Hardmanr pp 706-708.) Spironolactone is an aldosterone antagonist that acts on the mineralocorticoid receptor It is a Kksparing diuretic. It can also function as an androgen antagonist, which could explain the gynecomastia and erectile dysfunction. Women with hirsutism are sometimes treated with spironolactone. 

Spironolactone and eplerenone block the mineralocorticoid receptor, the target site for aldosterone. In the kidney, aldosterone antagonists inhibit sodium reabsorption and potassium excretion. However, diuretic effects are minimal, suggesting that their therapeutic benefits result from other... 

Aldosterone antagonists (spironolactone, eplerenone) are also potassium-sparing diuretics but are more potent antihypertensives with a slow onset of action (up to 6 weeks with spironolactone). 

An aldosterone antagonist may be considered in addition to a diuretic, ACE inhibitor or ARB, and /1-blocker. Regimens employing both an aldosterone antagonist and ARB are not recommended because of the potential risk of severe hyperkalemia. 

Aldactone containing spironolactone (potassium-sparing diuretic and an aldosterone antagonist) is used with caution in cases of porphyria. 

Spironolactone is a potassium-sparing diuretic. It is an aldosterone antagonist and potentiates the action of loop or thiazide diuretics. 

Hepatic cirrhosis-The usual initial dose is 5 or 10 mg once daily oral or IV, administered together with an aldosterone antagonist or a potassium-sparing diuretic. If the diuretic response is inadequate, titrate the dose upward by approximately doubling until the desired diuretic response is obtained. Single doses greater than 40 mg have not been adequately studied. 

Symptomatic or prior-symptomatic fluid retention responds well to treatment with diuretics and salt restriction if LVEF is reduced. This will usually improve current HF symptoms. Especially, an aldosterone antagonist like spironolactone should be added in selected patients with advanced HF symptoms and reduced LVEF with preserved renal function. Potassium has to be normal and should be carefully monitored. Patients with renal dysfunction and with serum creatinine levels >2.5 mg/dl in men and >2.0 mg/dl in women are contraindicated for aldosterone antagonists. 

Hepatic cirrhosis PO, IV Initially, 5 mg/day given with aldosterone antagonist orpo-tassium-sparing diuretic. May increase by approximately doubling dose until desired therapeutic effect is attained. Doses greater than 40 mg have not been adequately studied. 

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