Potential Roles of Aldosterone in the Pathophysiology of Heart Failure

Mechanism

Increased Na+ and water retention K+ and Mg2+ loss

Reduced myocardial norepinephrine uptake

Reduced baroreceptor sensitivity

Myocardial fibrosis, fibroblast proliferation Alterations in Na+ channel expression

Pathophysiological Effect

Edema, elevated cardiac filling pressures Arrhythmogenesis and risk of sudden cardiac death Potentiation of norepinephrine effects:

myocardial remodeling and arrhythmogenesis Reduced parasympathetic activity and risk of sudden cardiac death Remodeling and ventricular dysfunction Increased excitability and contractility of cardiac myocytes decreased motility of the bowel wall, and reduced splanchnic blood flow can delay or attenuate peak diuretic effect. Patients who have impaired renal function typically require higher doses of diuretic to ensure adequate delivery of the drug to its site of action. Following prolonged administration of a loop diuretic, a process of adaptation can occur in which there is a compensatory increase in Na+ reabsorption in the distal nephron and blunting of net Na+ and water loss. The more common causes of diuretic resistance are listed in Table 33-3 and discussed in Chapter 28.

The caveats about concomitant therapy merit particular emphasis when considering coadministration of diuretics and ACE inhibitors or ATl receptor antagonists. These inhibitors of the renin-angiotensin system can either augment or reduce the effectiveness of diuretics. A reduced response is observed most commonly in patients with decreased renal arterial perfusion pressure, due either to renal artery stenosis or to reduction of forward cardiac output. In such patients, a high level of AnglI-mediated glomerular efferent arteriolar tone is necessary to maintain glomerular filtration pressure. Pharmacologic antagonism of this intrarenal autoregulation may be accompanied by a decline in creatinine clearance and a derivative rise in the serum creatinine. In general, this is readily distinguished from the modest and limited rise in serum creatinine levels that commonly accompanies administration of ACE inhibitors. Diuretic resistance that reflects poor forward cardiac output may require the use of positive inotropic agents (e.g., dobutaminej as vasodilator therapy is initiated.

Decreased responsiveness to loop diuretics in patients with known chronic heart failure should prompt an increase in the dose administered or the dosing frequency. If this is ineffective, a thi-azide diuretic (e.g., hydrochlorothiazide or metolazone) administered with the loop diuretic is often effective. However, this combination can result in an unpredictable and sometimes excessive diuresis, leading to intravascular volume depletion and renal K+ wasting; the combination therefore should be used cautiously. Spironolactone also may be effective in these patients when combined with a loop diuretic.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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