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Pathway Description
Furosemide Diuretic Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2020-08-02
Last Updated: 2023-10-25
Furosemide is a loop diuretic drug, administered orally or intravenously to treat conditions such as hypertension or edema associated with to congestive heart failure, cirrhosis, liver disease and renal failure. It targets the nephrons of the kidney, mainly the ascending limb of the loop of henle.
The basolateral membrane of the ascending loop of henle, the Na+/K+ ATPase, Cl- channel and K+/Cl- co-transporter which are essential for the function for ion and water reabsorption. The Na+/K+ ATPase pumps Na+ from the cell into the peritubular fluid and K+ from the peritubular fluid into the cell. The K+/Cl- co-transporter moves K+ and Cl- from the cell into the peritubular fluid and the Cl- channel transports Cl- from the cell into the peritubular fluid.
The apical membrane contains the Na+/K+/2Cl- co-transporter (NKCC2) and the K+ channel. The NCKCC2 is responsible for reabsorption Na+, K+ and Cl- from the lumen into the cells of the loop of henle. The K+ channel transports K+ from the cells back into the lumen.
Furosemide is transported from the capillaries into the cells of the loop of henle via the OAT1 transporter (Solute carrier family 22 member 6). It is then transported from the cell into the lumen via multidrug resistant associated protein 4. Furosemide competes with Cl- for the NKCC2 transporter. It binds to this transporter, inhibiting it and preventing Na+, K+ and Cl- reabsorption from the lumen. The concentration of these ions builds up in the lumen, decreasing the slope of the concentration gradient between the cells and the lumen. Since water reabsorption is linked to ion reabsorption, water reabsorption is also decreased, resulting in a greater volume of water being excreted in urine. This is relieves symptoms such as swelling/ edema and hypertension in patients.
Furosemide may also inhibit sodium and chloride reabsorption in the proximal and distal tubules.
Side effects such as blurred vision, headache, diarrhea, constipation, fever, tinnitus, rash, jaundice, increased urination, dehydration, dizziness, nausea and vomiting, gout, hyperuricemia, muscle cramps may occur from taking furosemide.
References
Furosemide Diuretic Pathway References
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