10.10: Heart Failure Drugs: Diuretics
Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be maladaptive, exacerbating fluid retention and worsening heart failure symptoms. One such mechanism involves activating the renin-angiotensin-aldosterone system (RAAS), which leads to vasoconstriction and further fluid retention.
Diuretics have been a mainstay in managing fluid overload in heart failure patients. They work by inhibiting sodium reabsorption in the nephrons, increasing urine output, and reducing fluid overload. Loop diuretics, thiazide diuretics, and potassium-sparing diuretics are commonly used, each with unique mechanisms of action. Loop diuretics act on the thick ascending limb of the loop of Henle, blocking the sodium-potassium-chloride cotransporter. Thiazide diuretics work on the distal convoluted tubule, inhibiting the sodium-chloride symporter. Potassium-sparing diuretics inhibit sodium reabsorption in the collecting ducts while sparing potassium. Aldosterone or mineralocorticoid receptor antagonists (MRAs) like spironolactone and eplerenone are combined with diuretics. These MRAs inhibit the action of aldosterone, a hormone that promotes sodium retention and potassium excretion. By blocking this action, MRAs promote sodium excretion and potassium retention, aiding in fluid balance.
However, the use of diuretics has limitations. Overuse can lead to electrolyte imbalances, particularly hypokalemia and renal dysfunction. Also, diuretic resistance is a phenomenon in which the body becomes less responsive to diuretics over time. This underscores the need to monitor and manage diuretics in heart failure patients carefully.
