- Loop diuretic
Loop diuretics are
diuretic s that act on the ascendingloop of Henle in thekidney . They are primarily used inmedicine to treathypertension andedema often due tocongestive heart failure orrenal 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. Becausemagnesium andcalcium 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 hypertonicrenal medulla . Without such a concentrated medulla, water has less of an osmotic driving force to leave thecollecting duct system , ultimately resulting in increasedurine 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 thevein s and of the kidney'sblood vessel s, mechanically causing a decrease inblood 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 :
* edema associated with
heart failure , hepaticcirrhosis ,renal impairment ,nephrotic syndrome
*hypertension
* adjunct in cerebral/pulmonary edema where rapiddiuresis is required (IV injection)They are also sometimes used in the management of severe
hypercalcemia in combination with adequate rehydration .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 athiazide diuretic such ashydrochlorothiazide (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 , syncope cite book |editor=Rossi S |title=Australian Medicines Handbook 2004 |edition=5th |isbn=0-9578521-4-2 |url=http://www.amh.net.au/ ] .Infrequent ADRs include:
dyslipidemia , increased serumcreatinine concentration, hypocalcemia,rash .Ototoxicity (damage to theear ) is a serious, but rare ADR associated with use of loop diuretics. This may be limited totinnitus and vertigo, but may result indeafness in serious cases.Loop diuretics may also precipitate renal failure in patients concomitantly taking an
NSAID and anACE 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
*
Furosemide
*Bumetanide
*Ethacrynic acid
*Torsemide References
External links
* [http://www.fpnotebook.com/CV226.htm Loop Diuretic] , from the Family Practice Notebook
*
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См. также в других словарях:
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