Loop diuretics have a sigmoid dose-response curve with a threshold dose and ceiling dose.
Threshold Doses and Ceiling Doses in Loop Diuretics
Loop diuretics have a sigmoidal dose-responsive effect. Doses smaller than the threshold dose produce little or no diuretic effect. It takes increasing sizes of doses until diuresis occurs. That’s the threshold dose.
Loop diuretics also have a ceiling dose. This is the dose that shows the maximum fractional sodium excretion. Doses higher than the ceiling dose start to yield diminishing returns and are only slightly more effective. Increasing the frequency of dosing with the ceiling dose is more effective than increasing the dose of furosemide.
Both the threshold and ceiling dose varies depending on the patient characteristics or disease state.
For example, the threshold dose of IV furosemide is 10 mg in people with normal renal function. This increases to 80-160mg in patients with declining renal function. Therefore, a furosemide dose lower than 80 mg is not effective in advanced CKD patients.
The ceiling dose of IV furosemide is 80-200 mg in patients with CKD or nephrotic syndrome, and 40-80 mg in patients with CHF or liver cirrhosis.
For loop diuretics, the response is a function of the amount of drug excreted by the kidneys. Because of that, you need a larger dose in patients with renal insufficiency or CHF.
Loop Diuretics have different half-lives
- The half-life of the various loop diuretics are not the same: 1-1.5 hours for furosemide and 3-4 hours for torsemide.
- The half-life of furosemide is prolonged in advanced renal dysfunction, and the half-life of torsemide is doubled in hepatic dysfunction.
- Torsemide can be administered once daily while furosemide needs to be administered two or three times a day.
Reference
Oh SW, Han SY. Loop Diuretics in Clinical Practice. Electrolytes & Blood Pressure : E & BP. 2015;13(1):17-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520883/