- Loop diuretic
Loop diuretics are
diuretics that act on the ascending loop of Henlein the kidney. They are primarily used in medicineto treat hypertensionand edemaoften due to congestive heart failureor renal insufficiency.
Mechanism of action
Loop diuretics act on the Na+-K+-2Cl- symporter (cotransporter) in the thick ascending limb of the
loop of Henleto inhibit sodium and chloride reabsorption. This is achieved by competing for the Cl- binding site. Because magnesiumand calciumreabsorption 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 urineproduction. This diuresis leaves less water to be reabsorbed into the blood, resulting in a decrease in blood volume.
Loop diuretics also cause
vasodilationof the veins and of the kidney's blood vessels, mechanically causing a decrease in blood pressure.
The collective effects of decreased blood volume and vasodilation decrease blood pressure and ameliorate edema.
* edema associated with
heart failure, hepatic cirrhosis, renal impairment, nephrotic syndrome
* adjunct in cerebral/
pulmonary edemawhere rapid diuresisis required (IV injection)
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 thiazidediuretic 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
Common ADRs include:
hyponatremia, hypokalemia, hypomagnesemia, dehydration, hyperuricemia, gout, dizziness, postural hypotension, syncope cite book |editor=Rossi S |title= Australian Medicines Handbook2004 |edition=5th |isbn=0-9578521-4-2 |url=http://www.amh.net.au/ ] .
Infrequent ADRs include:
dyslipidemia, increased serum creatinineconcentration, hypocalcemia, rash. Ototoxicity(damage to the ear) is a serious, but rare ADR associated with use of loop diuretics. This may be limited to tinnitusand vertigo, but may result in deafnessin serious cases.
Loop diuretics may also precipitate renal failure in patients concomitantly taking an
NSAIDand an ACE inhibitor-- the so-called "triple whammy" effect [cite journal |author=Thomas MC |title=Diuretics, ACE inhibitors and NSAIDs--the triple whammy |journal=Med. J. Aust. |volume=172 |issue=4 |pages=184–5 |year=2000 |month=February |pmid=10772593 |doi= |url=] .
Examples of loop diuretics
* [http://www.fpnotebook.com/CV226.htm Loop Diuretic] , from the Family Practice Notebook
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Look at other dictionaries:
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