Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Dr Sukanta Sen
Congestive heart failure is the pathophysiologic state in
Loop Diuretics:
• Furosemide, bumetanide, and torsemide are widely used in the treatment of
CHF.
Q. Due to the increased risk of ototoxicity, ethacrynic acid is recommended
only for patients with sulfonamides allergies.
•Loop diuretics inhibit a specific ion transport protein, the Na+-K+-2Cl–
symporter on the apical membrane of renal epithelial cells in the ascending
limb of the loop of Henle to increase Na+ and fluid delivery to distal nephron
segments. These drugs also enhance K+ secretion, particularly in the presence
of elevated aldosterone levels, as is typical in CHF.
Thiazide Diuretics:
• Monotherapy with thiazide diuretics has a limited role in CHF. However,
combination therapy with loop diuretics is often effective in those refractory to
loop diuretics alone.
•Thiazide diuretics act on the Na+ Cl– co-transporter in the distal convoluted
tubule and are associated with a greater degree K+ wasting per fluid volume
reduction when compared to loop diuretics.
K+-Sparing Diuretics:
• K+-sparing diuretics inhibit apical membrane Na+-conductance channels in
renal epithelial cells (e.g., amiloride, triamterene) or are mineralocorticoid
(e.g., aldosterone) receptor antagonists (e.g., canrenone, spironolactone, and
eplerenone).
•Collectively, these agents are weak diuretics, but have been used to achieve
volume reduction with limited K+ and Mg2+ wasting.
Diuretics in Clinical Practice:
•The majority of CHF patients will require chronic administration of
a loop diuretic to maintain euvolemia. In patients with clinically
evident fluid retention, furosemide typically is started at a dose of 40
mg once or twice daily, and the dosage is increased until an adequate
diuresis is achieved.
•A larger initial dose may be necessary in patients with advanced CHF
and azotemia.
•Serum electrolytes and renal function are monitored frequently.
•If present, hypokalemia from therapy may be corrected by oral or
intravenous K+ supplementation or by the addition of a K+-sparing
diuretic.
Diuretics in the Decompensated Patient:
• In patients with decompensated CHF warranting hospital admission,
repetitive intravenously administered boluses or a constant infusion
titrated to achieve a desired response may be needed to provide
expeditious diuresis.
•A typical continuous furosemide infusion is initiated with a 40-mg
bolus injection followed by a constant rate of 10 mg/h, with
uptitration as necessary.
•If renal perfusion is reduced, drug efficacy may be enhanced by co-
administration of drugs that increase cardiac output (e.g.,
dobutamine).
ALDOSTERONE ANTAGONISTS
•LV systolic dysfunction decreases renal blood flow and results in
over-activation of the renin–angiotensin–aldosterone axis and may
increase circulating plasma aldosterone levels in CHF to 20-fold
above normal.
•The pathophysiologic effects of hyperaldosteronemia are diverse
and extend beyond Na+ and fluid retention; however, the precise
mechanism by which aldosterone receptor blockade improves
outcome in CHF remains unresolved.
•Aldosterone-receptor antagonists in combination with ACE inhibitor therapy have
provided beneficial effects in clinical trials. In CHF patients with low LV ejection fraction,
spironolactone (25 mg/day) decreased mortality by ~30% (from progressive heart failure or
sudden cardiac death), and patients had fewer CHF-related hospitalizations compared with the
placebo group.
•Treatment was well tolerated; however, 10% of men reported gynecomastia and 2% of all
patients developed severe hyperkalemia (>6.0 mEq/L).
Vasodilator Drugs Used to Treat Heart Failure
NITROVASODILATORS:
myocyte apoptosis.
• This increase in releasable Ca2+ (from the SR) is the mechanism by which
cardiac glycosides enhance myocardial contractility.