Question

Furosemide mechanism of action

• A. Inhibit Na⁺-K⁺-2Cl⁻ cotransporter in the ascending limb of Henle
• B. Inhibit Na⁺-K⁺ cotransporter in the collecting duct
• C. Inhibit Na⁺-2Cl⁻ cotransporter in the distal loop of Henle
• D. Aldosterone antagonist

Hint:

Furosemide is called a "high-ceiling" diuretic due to its powerful action. It may cause hypokalemia and ototoxicity with prolonged use.

Answer 1

The Correct Option is A

Furosemide is a loop diuretic that acts primarily on the thick ascending limb of the loop of Henle in the nephron. - It inhibits the Na⁺-K⁺-2Cl⁻ symporter, which is responsible for the reabsorption of sodium, potassium, and chloride ions from the tubular fluid back into the bloodstream.
- By blocking this transporter, furosemide increases the excretion of Na⁺, Cl⁻, and K⁺, along with water, leading to a potent diuretic effect.
- This inhibition also reduces the reabsorption of calcium and magnesium, contributing to additional electrolyte loss.
- Furosemide is useful in the management of edema, congestive heart failure, hypertension, and renal impairment.
- Unlike thiazide diuretics, which act on the distal convoluted tubule, furosemide works earlier in the nephron and has a more profound diuretic effect.

Answer 2

Different classes of diuretics act at different sites along the nephron, and identifying furosemide's exact site and target explains why it is called a loop diuretic. Checking each option against where and how furosemide actually works confirms the answer.

1. Inhibit Na+-K+-2Cl- cotransporter in the ascending limb of Henle: Furosemide binds this specific cotransporter in the thick ascending limb, stopping the reabsorption of sodium, potassium, and chloride back into the blood at this site. Because the ascending limb normally handles a large share of sodium reabsorption, blocking this one transporter produces a powerful diuretic effect, and it also disrupts the concentration gradient the kidney needs to reabsorb water later on, adding to the diuresis.
2. Inhibit Na+-K+ cotransporter in the collecting duct: The collecting duct does not use this type of cotransporter for sodium handling, and this is not furosemide's site or mechanism of action.
3. Inhibit Na+-2Cl- cotransporter in the distal loop of Henle: This describes neither the correct transporter (it is missing the potassium component) nor the correct segment, since furosemide acts on the ascending limb, not a distal loop segment.
4. Aldosterone antagonist: Blocking aldosterone receptors describes potassium-sparing diuretics like spironolactone, which act in the collecting duct, a completely different class and site from furosemide.

Furosemide's defining action is blocking the specific triple cotransporter in the thick ascending limb of the loop of Henle, which is why it is classified as a loop diuretic.

So the correct answer is Inhibit Na+-K+-2Cl- cotransporter in the ascending limb of Henle.