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Loop diuretics: Maximum effective dose and major side effects

D Craig Brater, MD
Section Editors
Richard H Sterns, MD
Michael Emmett, MD
Deputy Editor
John P Forman, MD, MSc


Loop diuretics reduce NaCl reabsorption in the thick ascending limb of the loop of Henle. This is achieved by inhibiting the Na-K-2Cl carrier in the luminal membrane in this segment, thereby minimizing the entry of luminal sodium into the cell [1]. The loop diuretics are highly protein-bound and therefore enter the urine primarily by tubular secretion in the proximal tubule, rather than by glomerular filtration [1].

The effect of the loop diuretics is dose dependent, being determined largely by the rate at which the diuretic is delivered to its site of action (figure 1) [2]:

No diuresis is seen with very low doses

A progressively increasing diuresis is achieved at higher doses

A plateau is reached at which even higher doses produce no further diuresis; this dose is called the maximum effective dose, which increases with worsening renal function


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Literature review current through: Sep 2016. | This topic last updated: Jul 1, 2015.
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