What is the effect of Furosemide (Lasix), a loop diuretic?

From the Guidelines

Furosemide should be initiated at a dose of 20-40mg once or twice daily, with a maximum total daily dose of 600mg, to manage fluid overload conditions such as edema associated with heart failure, liver disease, and kidney disease, as well as for managing hypertension, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

Key Considerations

• The dose of furosemide may need to be increased until urine output increases and weight decreases, generally by 0.5 to 1.0 kg daily, and the ultimate goal of diuretic treatment is to eliminate clinical evidence of fluid retention, such as jugular venous pressure elevation and peripheral edema 1.
• Patients should monitor for side effects including electrolyte imbalances (particularly potassium depletion), dehydration, and increased blood glucose, and regular blood tests to check kidney function and electrolyte levels are important during treatment 1.
• Furosemide can interact with other medications including NSAIDs, aminoglycoside antibiotics, and lithium, so a complete medication review is essential before starting therapy 1.

Diuretic Resistance

• Diuretic resistance can be overcome by the intravenous administration of diuretics, the use of 2 or more diuretics in combination, or the use of diuretics together with drugs that increase renal blood flow 1.
• Patients may become unresponsive to high doses of diuretic drugs if they consume large amounts of dietary sodium, are taking agents that can block the effects of diuretics, or have a significant impairment of renal function or perfusion 1.

Clinical Evidence

• The 2022 AHA/ACC/HFSA guideline for the management of heart failure recommends the use of loop diuretics, such as furosemide, for the treatment of fluid overload conditions, and provides guidance on the initiation and maintenance of diuretic therapy 1.
• Other studies have demonstrated the effectiveness of furosemide in managing fluid overload conditions, but also highlight the importance of careful titration to avoid worsening renal function 1.

From the FDA Drug Label

Investigations into the mode of action of Furosemide tablets have utilized micropuncture studies in rats, stop flow experiments in dogs and various clearance studies in both humans and experimental animals It has been demonstrated that Furosemide tablets inhibits primarily the absorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle. The onset of diuresis following oral administration is within 1 hour. The peak effect occurs within the first or second hour. The duration of diuretic effect is 6 to 8 hours Furosemide is predominantly excreted unchanged in the urine The renal clearance of furosemide after intravenous administration in older healthy male subjects (60-70 years of age) is statistically significantly smaller than in younger healthy male subjects (20-35 years of age).

The mechanism of action of furosemide is the inhibition of sodium and chloride absorption in the proximal and distal tubules and the loop of Henle.

• The onset of action is within 1 hour.
• The peak effect occurs within the first or second hour.
• The duration of action is 6 to 8 hours.
• Furosemide is excreted unchanged in the urine.
• Renal clearance is reduced in older subjects compared to younger subjects 2.

From the Research

FUROSEMIDE Overview

• Furosemide is a type of loop diuretic used to treat patients with diseases characterized by excess extracellular fluid, including chronic kidney disease, the nephrotic syndrome, cirrhosis, and heart failure 3.
• Loop diuretics, such as furosemide, are typically the first-line treatment in the management of hypervolemia, with additional drug classes indicated in cases of diuretic resistance and electrolyte or acid-base disorders 4.

Clinical Use of Furosemide

• Furosemide has been compared to bumetanide in patients with edema associated with congestive heart failure, and both agents were found to be highly effective in reducing edema and relieving symptoms of heart failure 5.
• The use of furosemide in congestive heart failure is aimed at relieving congestive symptoms, but its use can be challenging due to complications like electrolyte abnormalities, worsening renal function, and diuretic resistance 6.
• A conceptual framework has been presented to maximize the chance for achieving adequate volume removal while maintaining stable or improved renal function during the treatment of acute decompensated heart failure with loop diuretics like furosemide 7.

Adverse Effects and Considerations

• Diuretic-related adverse events, including those involving the uric acid, Na+, and K+ axes, are not uncommon, and clinicians must be vigilant in looking for biochemical disturbances 3.
• Muscle cramps and abdominal pain have been reported as side effects of furosemide, although they were deemed not severe in one study 5.
• Laboratory values indicative of mild hypochloremic alkalosis and hyponatremia have been observed in patients treated with furosemide 5.