Loop Diuretics

2. Loop Diuretics
Loop diuretics block the NKCC channel at the Thick Ascending Loop of Henle. This prevents the reabsorption of Na+, K+, and Cl-. Therefore there is no the potential difference formation, so other solutes (Ca2+ and Mg2+) are also not reabsorbed. In addition to the excretion of Na+, K+, Cl-, Ca2+, Mg2+, there is also increased excretion of titratable acid and decreased excretion of uric acid (gout). Furosemide is a sulfonamide drug. Ethacrynic acid is not. Loop diuretics are highly efficacious as other segments of the nephron are unable to compensate. Furosemide causing venodilation, reducing preload before diuresis occurs. The inhibition of salt transport into the macula densa (low Na+) and the volume depletion (baroreceptor) causes an increase in renin which increases GFR.

Diuretics can evoke compensatory mechanisms such as activation of SNS, RAAS, and decrease BP. These can lead to diuretic resistance or braking phenomenon. For Furosemide, the transporter in the proximal tubule may be blocked so that the drug cannot be secreted into the lumen and travel to the site of action.

Loop diuretics can be used to treat:
-acute pulmonary edema
-congestive heart failure
-nephrotic syndrome
-liver cirrhosis
-chronic kidney disease
-acute kidney injury
-hypertension
-drug overdose
-hypercalcemia

Adverse effects to loop diuretics include:
-hyponatremia
-hypokalemia
-hypomagnesemia
-metabolic alkalosis
-ototoxicity

Contradictions to loop diuretics include:
-pregnancy

Drug interactions with loop diuretics include:
-NSAIDs (block COX-2 --> decreased prostaglandin --> decreased vasodilation --> decreased GFR --> blunted response because not much is filtered)
-ACE inhibitors and ARB (enhanced nephrotoxicity)
-Lithium (enhanced Na+ excretion so lithium toxicity)
-Digitalis glycosides (hypokalemia --> arrhythmia)
-Quinidine (hypokalemia --> torsades de pointe)
-Probenecid (blocks OAT so drug can't get in)
-Aminoglycosides and cisplatin (ototoxicity)
-Amphotericin B (hypokalemia)
-Glucocorticoids (hypokalemia)