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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. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.
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 (primarily on the recycling of the potassium due to the lack of the electropositive gradient generation), 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. Loop diuretics cause a decrease in the renal blood flow by this mechanism. 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 :
- edema associated with heart failure, hepatic cirrhosis, renal impairment, nephrotic syndrome
- adjunct in cerebral/pulmonary edema where rapid diuresis is 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 thiazide diuretic such as hydrochlorothiazide (to inhibit sodium reabsorption at multiple sites in the nephron) is often successful. Newly emerging evidence shows that glucocorticoids may be use to reverse the loop diuretic resistance in heart failure.
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.
Examples of loop diuretics
- Rossi S, ed. (2004). [[Australian Medicines Handbook]] 2004 (5th ed.). Adelaide, S.A.: Australian Medicines Handbook Pty Ltd. ISBN 0-9578521-4-2. Wikilink embedded in URL title (help)
- Liu, C; Liu, G; Zhou, C; Ji, Z; Zhen, Y; Liu, K (2007 Sep). "Potent diuretic effects of prednisone in heart failure patients with refractory diuretic resistance.". The Canadian journal of cardiology 23 (11): 865–8. PMID 17876376.
- Massari, F; Mastropasqua, F; Iacoviello, M; Nuzzolese, V; Torres, D; Parrinello, G (2012 Mar). "The glucocorticoid in acute decompensated heart failure: Dr Jekyll or Mr Hyde?". The American journal of emergency medicine 30 (3): 517.e5–10. PMID 21406321.
- Thomas MC (February 2000). "Diuretics, ACE inhibitors and NSAIDs--the triple whammy". Med. J. Aust. 172 (4): 184–5. PMID 10772593.
- Loop Diuretic, from the Family Practice Notebook
- Loop Diuretics at the US National Library of Medicine Medical Subject Headings (MeSH)