USMLE Step 3 Drug MOA Practice Test 2025 – Complete All-in-One Guide to Exam Mastery!

Loop diuretics, such as furosemide, exert their pharmacological effects primarily by inhibiting the Na+/K+/2Cl- co-transporter (also known as the NKCC2 transporter) located in the thick ascending limb of the loop of Henle in the kidney. By blocking this transporter, loop diuretics prevent the reabsorption of sodium, potassium, and chloride ions from the tubular lumen back into the blood. This action leads to a significant increase in the urinary excretion of these electrolytes and water, resulting in diuresis.

The disruption of sodium and chloride reabsorption contributes to a decrease in the osmotic gradient necessary for water reabsorption in the nephron, which helps to reduce fluid overload and is beneficial in conditions such as heart failure, edema, and hypertension. Additionally, the inhibition of the Na+/K+/2Cl- co-transporter has implications for calcium and magnesium reabsorption, often resulting in increased excretion of these ions as well.

The other answer choices represent mechanisms of action of different drugs or pathways that do not relate to the action of loop diuretics.