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Loop diuretics are diuretics that act on the ascending loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency.
Mechanism of action
Loop diuretics act on the Na+-K+-2Cl- symporter (cotransporter) in the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption. This is achieved by competing for the Cl- binding site. Because magnesium and calcium reabsorption in the thick ascending limb is dependent on sodium and chloride concentrations, loop diuretics also inhibit their reabsorption. By disrupting the reabsorption of these ions, loop diuretics prevent the urine from becoming concentrated and disrupt the generation of a hypertonic renal medulla. 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. This diuresis leaves less water to be reabsorbed into the blood, resulting in a decrease in blood volume.
The collective effects of decreased blood volume and vasodilation decrease blood pressure and ameliorate edema.
Loop diuretics are principally used in the following indications (Rossi, 2004):
They are also sometimes used in the management of severe hypercalcemia in combination with adequate rehydration (Rossi, 2004).
Loop diuretic resistance
Renal insufficiency causes decreased bloodflow to the kidneys, which decreases the glomerular filtration rate (GFR) and reduces the ability of loop diuretics to reach their target organ, the loop of Henle. Similarly, non-steroidal anti-inflammatory drugs also decrease GFR with comparable results. In patients with reduced GFR, ceiling dosages of loop diuretics are increased proportional to the decrease in GFR. Simultaneous treatment with a thiazide diuretic such as hydrochlorothiazide (to inhibit sodium reabsorption at multiple sites in the nephron) is often successful.
Patients with congestive heart failure tend to retain sodium, also necessitating an increase in dosage. The same is true for patients with increased sodium intake.
The most common adverse drug reactions (ADRs) are dose-related and relate to the effect of loop diuretics on diuresis and electrolyte balance.
Loop diuretics may also precipitate renal failure in patients concomitantly taking an NSAID and an ACE inhibitor -- the so-called "triple whammy" effect (Thomas, 2000).
Examples of loop diuretics
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Loop_diuretic". A list of authors is available in Wikipedia.|