What is the mechanism of action of a loop diuretic (Loop Diuretic)

From the Guidelines

Loop diuretics should be used in combination with aldosterone antagonists for the treatment of ascites in patients with liver cirrhosis, with furosemide being a commonly used loop diuretic, started at a dose of 20-40 mg/day. The use of loop diuretics in patients with liver cirrhosis is supported by the 2018 guidelines for liver cirrhosis, which recommend the use of diuretics in cases of ascites Grade 2 or 3 1. Loop diuretics act on the Na-K-2Cl receptors in the thick ascending limb of Henle’s loop, and furosemide is a representative loop diuretic with a rapid onset of action.

Some key points to consider when using loop diuretics include:

• Monitoring electrolytes, kidney function, and blood pressure regularly to avoid significant electrolyte imbalances and dehydration
• Starting with a low dose and adjusting as needed to minimize side effects
• Using loop diuretics in combination with aldosterone antagonists, such as spironolactone, to maintain adequate serum potassium levels
• Avoiding monotherapy with loop diuretics, as this is not recommended 1

It's also important to note that loop diuretics can cause side effects such as hypokalemia, and should be reduced or stopped in case of hypokalemia 1. Additionally, diuretics should be used in as small a dose as possible when the ascites is controlled to prevent complications, and should be stopped and the patient’s status reevaluated in cases of hepatic encephalopathy, hyponatremia, acute kidney injury, or lack of response in weight with a low-salt diet 1.

The 2009 guidelines for the diagnosis and management of heart failure in adults also support the use of loop diuretics, such as furosemide, bumetanide, and torsemide, for the treatment of edema associated with heart failure, liver cirrhosis, and kidney disease 1. However, the most recent and highest quality study, which is the 2018 guidelines for liver cirrhosis, should be prioritized when making treatment decisions 1.

From the FDA Drug Label

Micropuncture studies in animals have shown that torsemide acts from within the lumen of the thick ascending portion of the loop of Henle, where it inhibits the Na+/K+/2Cl–-carrier system. The major site of bumetanide action is the ascending limb of the loop of Henle Loop Diuretic Mechanism:

• Torsemide and bumetanide are loop diuretics that act on the thick ascending portion of the loop of Henle.
• They inhibit the Na+/K+/2Cl–-carrier system, which leads to increased excretion of sodium, chloride, and water.
• The onset of diuresis for torsemide occurs within 1 hour, while bumetanide has a rapid onset of action, with diuresis starting within minutes after intravenous injection 2, 3.

From the Research

Loop Diuretics Overview

• Loop diuretics are a class of medications used to treat fluid build-up (edema) and swelling that is caused by various medical conditions such as heart failure, liver disease, and kidney disease.
• The most commonly used loop diuretics are furosemide, torsemide, and bumetanide.

Comparison of Loop Diuretics

• Studies have compared the effectiveness of furosemide, torsemide, and bumetanide in patients with heart failure, with some studies suggesting that torsemide may be more effective than furosemide in reducing mortality and hospitalizations 4, 5, 6.
• Torsemide has been shown to have a more favorable pharmacokinetic profile compared to furosemide, with less inter- and intra-individual variation in bioavailability and a longer duration of action 4, 6.
• Bumetanide has also been shown to be effective in patients with heart failure, although the evidence is less consistent compared to torsemide 4, 5.

Clinical Use of Loop Diuretics

• Furosemide is the most widely prescribed loop diuretic, but torsemide and bumetanide are increasingly being used in clinical practice due to their potential benefits 4, 5, 6.
• Continuous infusion of loop diuretics, such as furosemide and bumetanide, has been shown to be effective in selected patient populations, including those with congestive heart failure and renal insufficiency 7.
• The choice of loop diuretic should be based on individual patient characteristics and medical history, as well as the specific clinical condition being treated.

Safety and Efficacy

• Torsemide has been shown to have a more favorable safety profile compared to furosemide, with a reduced risk of hypokalemia (low potassium levels) 8.
• The efficacy of loop diuretics can vary depending on the specific clinical condition being treated, as well as the individual patient's response to the medication 4, 5, 6.