From the Guidelines
Loop diuretics increase urine output by inhibiting the reabsorption of sodium or chloride at specific sites in the renal tubules, specifically at the loop of Henle, leading to an increase in sodium excretion and enhancement of free water clearance. This mechanism is supported by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, as stated in the 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults 1. The loop diuretics, such as bumetanide, furosemide, and torsemide, act by inhibiting the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle, preventing the reabsorption of sodium, potassium, and chloride ions, and creating an osmotic gradient that draws water into the tubule, significantly increasing urine volume.
The effects of loop diuretics on urine output are dose-dependent, and the dose may need to be increased until urine output increases and weight decreases, generally by 0.5 to 1.0 kg daily, as stated in the 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults 1. Common loop diuretics include furosemide (Lasix), bumetanide (Bumex), torsemide (Demadex), and ethacrynic acid (Edecrin), with furosemide being typically dosed at 20-80 mg orally or intravenously, and bumetanide being about 40 times more potent (0.5-2 mg doses). These medications work rapidly, with IV administration producing effects within minutes and oral administration within 30-60 minutes.
Some key points to consider when using loop diuretics include:
- Monitoring of fluid status and electrolytes is essential to prevent side effects such as electrolyte imbalances (particularly hypokalemia), dehydration, and metabolic alkalosis.
- Loop diuretics reduce medullary hypertonicity, further impairing water reabsorption in the collecting ducts.
- The ultimate goal of diuretic treatment is to eliminate clinical evidence of fluid retention, such as jugular venous pressure elevation and peripheral edema.
- Diuretics are generally combined with moderate dietary sodium restriction.
From the Research
Mechanism of Action
- Loop diuretics increase urine output by inhibiting sodium reabsorption in the renal tubules, resulting in increased urinary sodium and water excretion 2, 3.
- The sodium-potassium-chloride transporter in the loop of Henle plays a key role in the diuretic response to loop diuretics, and its expression or activity may be affected by various factors 4.
Clinical Effects
- Loop diuretics are the most potent diuretics and are commonly used to control edema in various clinical fields 2.
- They increase the clearance of electrolytes and water, allowing for control of hypervolemia and prevention of pulmonary edema 5.
- Loop diuretics are also used to prevent acute kidney injury (AKI) in certain situations, as long as euvolemia is maintained 5.
Pharmacokinetics and Pharmacodynamics
- The bioavailability of loop diuretics, such as furosemide, differs between oral and intravenous therapy 2.
- The threshold and ceiling doses of loop diuretics differ according to the particular clinical condition of the patient 2.
- The mode of delivery and dosage of loop diuretics must be carefully considered to maximize their efficiency 2, 3.