[4] They are often used for the treatment of hypertension and edema secondary to congestive heart failure, liver cirrhosis, or chronic kidney disease.

[5] Loop diuretics are 90% bonded to proteins and are secreted into the proximal convoluted tubule through organic anion transporter 1 (OAT-1), OAT-2, and ABCC4.

At the same time, loop diuretics inhibit the tubuloglomerular feedback mechanism so that increase in salts at the lumen near macula densa does not trigger a response that reduces the GFR.

Without such a concentrated medulla, water has less of an osmotic driving force to leave the collecting duct system, ultimately resulting in increased urine production.

[8][9] Prostaglandin-mediated vasodilation of preglomerular afferent arterioles increases the glomerular filtration rate (GFR) and facilitates diuresis.

[citation needed] Loop diuretics are highly protein bound and therefore have a low volume of distribution.

Also, there is a threshold minimum concentration of loop diuretics that needs to be achieved at the thick ascending limb to enable the onset of abrupt diuresis.

This is the body physiological response to reduced extracellular fluid volume, where renin-angiotensin-aldosterone system will be activated which results in nephron remodelling.

These cells have sodium-chloride symporter at distal convoluted tubule, epithelial sodium channels, and chloride-bicarbonate exchanger pendrin.

[6] The most common adverse drug reactions (ADRs) are dose-related and arise from the effect of loop diuretics on diuresis and electrolyte balance.

[citation needed] Common ADRs include: hyponatremia, hypokalemia, hypomagnesemia, dehydration, hyperuricemia, gout, dizziness, postural hypotension, syncope.

[citation needed] Loop diuretics may also precipitate kidney failure in patients concurrently taking an NSAID and an ACE inhibitor—the so-called "triple whammy" effect.

It carries a greater risk of reversible or permanent hearing loss (ototoxicity),[23] and has a distinct complication of being associated with gastrointestinal toxicity.