Chapter: Modern Pharmacology with Clinical Applications: Pharmacological Management of Chronic Heart Failure


One cannot discuss the management of heart failure without including comments about the kidney.


One cannot discuss the management of heart failure without including comments about the kidney. The rela-tionship between the heart and the kidney makes intu-itive sense when one considers the importance of the kidney in maintaining an appropriate volume status throughout the body. An analogy that may be useful to consider is the situation in which an individual turns on the faucet at home to find that little water is flowing. The first assumption is that a leak somewhere in the sys-tem is responsible for the lower water pressure. An ap-propriate response is to turn off the water to the house. In an analogous manner, the kidney perceives low car-diac output from a failing heart as a leak. The kidney be-gins to elaborate hormones designed to retain fluid. Many of the problems in CHF result from an inappro- priate neurohumoral activation by the kidney in re-sponse to perceived volume depletion from hemor-rhage. Mechanisms that result in vasoconstriction are normally compensatory in the short term for acute bleeding. These same adaptive mechanisms become damaging in chronic heart failure.

The usefulness of diuretics in the management of CHF cannot be overstated. Before diuretics were avail-able, rotating tourniquets were used to diminish venous return by ligating the lower extremities. Less venous blood returned to the right side of the heart and pooled in the legs. This procedure diminished the effective in-travascular volume that would otherwise have accumu-lated in the lungs. The availability of loop diuretics (par-ticularly furosemide) has resulted in the virtual elimination of this practice.

Loop Diuretics

Diuretics and their mechanisms of action will be dis-cussed in detail. Loop diuretics, such as furosemide (Lasix), block the NA+ –K+ –2Cl- symporter in the ascending limb of the loop of Henle. The resultant effect is delivery of more NA+ to the distal tubule and enhanced urinary loss of NA+ and water. Unfortunately, the resultant increase in urinary excretion of H+ and K+ can lead to arrhythmias. The potential for arrhythmias is exacerbated by the loss of Mg and Ca++ and an un-derlying vulnerability of the myocardium in CHF. However, loop diuretics are still part of the mainstay of therapy for CHF despite these potential problems and the absence of well-controlled multicenter clinical trials. The rationale for their use is so compelling that placebo-controlled studies appear unethical. Moreover, furosemide was accepted as the standard of care in all of the clinical trials that form the basis for recom-mended therapy for CHF. The use of the potassium-sparing diuretic spironolactone has been shown to im-prove survival and is discussed below.


Spironolactone (Aldactone) is the only diuretic that has been shown in a double-blind multicenter prospective clinical trial to improve survival in CHF. The addition of spironolactone to digitalis and an angiotensin-converting enzyme (ACE) inhibitor significantly im-proved survival among patients with chronic severe heart failure. This study was conducted with patients who were not taking a β-adrenoceptor blocking agent. It is unclear at present whether the addition of spirono-lactone to a combination of digitalis,ACE inhibitor, and a β-blocker will also confer additional benefit.

Spironolactone competitively inhibits the binding of aldosterone to cytosolic mineralocorticoid receptors in the epithelial cells in the late distal tubule and collect-ing duct of the kidney. Aldosterone enhances salt and water retention at the expense of enhanced renal K+ and H+ excretion. Spironolactone enhances diuresis by blocking sodium and water retention while retaining potassium. An obvious potential side effect is hyper-kalemia, which is aggravated by the potassium-retaining properties of the ACE inhibitors. The likely concomi-tant use of the loop diuretic furosemide, which depletes K+ , dictates careful monitoring of serum potassium to avoid life-threatening rhythm disturbances.

There is also evidence for the existence of mineralo-corticoid receptors on cardiac myocytes. This raises the intriguing possibility that spironolactone could mediate important direct effects on the myocardium in CHF.

Study Material, Lecturing Notes, Assignment, Reference, Wiki description explanation, brief detail
Modern Pharmacology with Clinical Applications: Pharmacological Management of Chronic Heart Failure : Diuretics |

Privacy Policy, Terms and Conditions, DMCA Policy and Compliant

Copyright © 2018-2023; All Rights Reserved. Developed by Therithal info, Chennai.