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Loop Diuretic

  • Loop Diuretics refer to a class of diuretics that function by inhibiting the Na2ClK symporter of the thick ascending loop of Henle (See: Thick Ascending Loop of Henle Transport). Loop diuretics represent the most powerful diuretics of sodium and and can yield rapid loss of extracellular volume. Consequently, they are some of the most commonly used drugs for treatment of heart failure due to volume overload.
Mechanism of Action
  • As mentioned, loop diuretics act at the level of the ascending henle and inhibit the Na2ClK symporter. This segment of the nephron is responsible for resorbing roughly 25% of the tubular salt and distal segments have limited reserve to compensatorily increase sodium resorption. As a consequence, loop diuretics are able to result in massive amounts of Na+ and Cl- diuresis. Because water osmotically follows this diuresed sodium, loop diuretics are highly effective at reducing extracellular volume. Consequently, they are typically the go-to drug in settings of volume overload.
Adverse Effects
  • Hypokalemia
    • Loop diuretics result in significant increases in the flow of sodium-rich fluid through the late distal tubule and collecting duct. As discussed under "Distal Tubular Flow Rate" of the External Potassium Balance page, this increased fluid delivery to the late distal tubule enhances sodium/potassium exchange, leading to increased potassium excretion. Patients typically become hypokalemic and frequently require potassium supplementation.
  • Hypocalcemia and Hypomagnesemia
    • As mentioned in Thick Ascending Loop of Henle Transport, the trans-membrane potential difference generated by the Na2ClK Symporter is used to resorb calcium and magnesium ions in the thick Henle. When this transport is blocked by loop diuretics, calcium and magnesium resorption are inhibited and thus their urinary excretion is enhanced. In some patients this can lead to hypocalcemia and hypomagnesemia.
  • Hyperuricemia
    • During the acute phase of treatment, loop diuretics inhibit urinary uric acid secretion and may yield hyperuricemia
  • Ototoxicity
    • At high doses or during rapid administration loop diuretics can result in ototoxicity, especially when administered with other ototoxic drug. For the sake of interest this may be due to the capacity of loop diuretics to change the electrolyte balance within the inner ear endolymph.
Member Drugs
  • Furosemide (Lasix)
  • Bumetadine (Bumex)