Which diuretic causes more diuresis, acetazolamide (Carbonic Anhydrase Inhibitor) versus furosemide (Loop Diuretic)?

From the Guidelines

Furosemide causes more diuresis than acetazolamide. Furosemide (Lasix) is a loop diuretic that inhibits the sodium-potassium-chloride cotransporter in the thick ascending limb of the loop of Henle, blocking reabsorption of 20-25% of filtered sodium and producing a robust diuretic effect, as supported by the European Society of Cardiology guidelines 1. Typical doses range from 20-80 mg orally or intravenously, with effects beginning within 30-60 minutes and lasting 6-8 hours. In contrast, acetazolamide (Diamox) is a carbonic anhydrase inhibitor that works in the proximal tubule and only blocks reabsorption of about 5% of filtered sodium, resulting in a much milder diuretic effect. The American College of Cardiology Foundation/American Heart Association task force on practice guidelines also recommends the use of loop diuretics, such as furosemide, for the treatment of heart failure, highlighting their effectiveness in promoting diuresis 1. Key points to consider when choosing between furosemide and acetazolamide include:

• The mechanism of action: Furosemide acts on the loop of Henle, while acetazolamide acts on the proximal tubule
• The potency of the diuretic effect: Furosemide is more potent than acetazolamide
• The typical indications for each medication: Furosemide is commonly used for heart failure and severe edema, while acetazolamide is used for glaucoma, altitude sickness, and metabolic alkalosis.

From the Research

Diuretic Comparison

• The diuretic effect of acetazolamide versus furosemide has been studied in various clinical trials 2, 3, 4, 5.
• A pilot study found that adjunctive acetazolamide with furosemide maintained a greater urine output response to furosemide over 24 hours, with 100% probability, compared to furosemide alone 2.
• Another study found that the addition of acetazolamide to the background diuretic regimen in patients with chronic heart failure exacerbations produced an additional diuretic effect and alleviation of dyspnea 3.
• However, a comparative study of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure patients found that furosemide plus metolazone resulted in the highest weight of sodium excreted and urine volume, compared to furosemide alone and furosemide plus acetazolamide 4.
• The efficacy of oral acetazolamide as add-on diuretic therapy in decongestion in patients with heart failure is currently being investigated in a randomized controlled trial 5.

Key Findings

• Acetazolamide may increase diuretic efficacy and counterbalance furosemide-induced metabolic alkalosis without safety concerns 2.
• The combination of furosemide and acetazolamide may be effective in achieving decongestion in patients with heart failure 3, 5.
• Furosemide plus metolazone may be more effective than furosemide plus acetazolamide in terms of sodium excretion and urine volume 4.

Study Limitations

• The studies had small sample sizes and were limited by their pilot or single-center design 2, 3, 5.
• The comparative study of diuretic regimens had a higher incidence of worsening renal function with furosemide plus metolazone compared to furosemide alone and furosemide plus acetazolamide 4.