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'''Loop diuretics''' are [[diuretic]]s 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|Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>-</sup> 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<sup>-</sup> 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 pressure|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.

Loop diuretics also cause [[vasodilation]] of the [[vein]]s and of the kidney's [[blood vessel]]s, mechanically causing a decrease in [[blood pressure]].

The collective effects of decreased blood volume and vasodilation decrease blood pressure and ameliorate edema.

==Clinical use==
Loop diuretics are principally used in the following indications (Rossi, 2004):

* edema associated with [[heart failure]], hepatic [[cirrhosis]], [[renal impairment]], [[nephrotic syndrome]]
* [[hypertension]]
* adjunct in [[cerebral edema|cerebral]]/[[pulmonary edema]] where rapid [[diuresis]] is required ([[intravenous|IV]] injection)

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 drug]]s 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.

== Adverse effects ==

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

Common ADRs include: [[hyponatremia]], [[hypokalemia]], [[hypomagnesemia]], [[dehydration]], [[hyperuricemia]], [[gout]], [[dizziness]], [[postural hypotension]], [[Fainting|syncope]] (Rossi, 2004).

Infrequent ADRs include: [[dyslipidemia]], increased serum [[creatinine]] concentration, hypocalcemia, [[rash]] (Rossi, 2004).

[[Ototoxicity]] (damage to the [[ear]]) is a serious, but rare ADR associated with use of loop diuretics. This may be limited to [[tinnitus]] and [[Vertigo (medical)|vertigo]], but may result in [[deafness]] in serious cases.

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 ==
* [[Furosemide]]
* [[Bumetanide]]
* [[Ethacrynic acid]]
* [[Torsemide]]

==References==
* Rossi S (Ed.) (2004). ''[[Australian Medicines Handbook]] 2004''. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
* Thomas, MC (2000). Diuretics, ACE inhibitors and NSAIDs -- the triple whammy. ''Med J Aust'' '''172''', 184&ndash;185. PMID 10772593

== External links ==
* [http://www.fpnotebook.com/CV226.htm Loop Diuretic], from the Family Practice Notebook
* {{MeshName|Loop+Diuretics}}


{{Antihypertensives and diuretics}}

[[Category:Loop diuretics|*]]
[[Category:Drugs]]


[[de:Schleifendiuretikum]]
[[fr:Diurétique de l'anse]]
[[pl:Diuretyki pętlowe]]
[[pt:Diurético de alça]]

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