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20-September-2008 09:55:49 - Loop diuretic August 2008 Chemical structures of some loop diuretics. Chemical structures of some loop diuretics. 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. Contents 1 Mechanism of action 2 Clinical use 3 Loop diuretic resistance 4 Adverse effects 5 Examples of loop diuretics 6 References 7 External links 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. Loop diuretics also cause vasodilation of 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. Clinical use Loop diuretics are principally used in the following indications 1: edema associated with heart failure, hepatic cirrhosis, renal impairment, nephrotic syndrome hypertension adjunct in cerebral/pulmonary edema where rapid diuresis is required IV injection They are also sometimes used in the management of severe hypercalcemia in combination with adequate rehydration 1. 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. 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 1. Infrequent ADRs include: dyslipidemia, increased serum creatinine concentration, hypocalcemia, rash . 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, 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 2. Examples of loop diuretics Furosemide Bumetanide Ethacrynic acid Torsemide References ^ a b c in Rossi S: Australian Medicines Handbook 2004, 5th. ISBN 0-9578521-4-2. ^ Thomas MC February 2000. Diuretics, ACE inhibitors and NSAIDs--the triple whammy. Med. J. Aust. 172 4: 184-5. PMID 10772593. External links Loop Diuretic, from the Family Practice Notebook MeSH Loop+Diuretics v d e Antihypertensives C02 and diuretics C03 Sympatholytic agents Centrally acting/antiadrenergics α2 agonist Clonidine, Guanfacine, Methyldopa imidazoline receptor agonist Moxonidine, Rilmenidine adrenergic uptake inhibitor Rescinnamine, Reserpine Ganglion-blocking/nicotinic antagonist Mecamylamine, Trimethaphan Peripherally acting/antiadrenergics α1 blockers: Prazosin Indoramin Trimazosin Doxazosin Urapidil Guanidine derivatives: Betanidine Guanethidine Guanoxan Debrisoquine Guanoclor Guanazodine Guanoxabenz Vasodilators Diazoxide hydrazinophthalazine Hydralazine, Dihydralazine, Endralazine, Cadralazine Minoxidil Nitroprusside Phentolamine Other antihypertensives serotonin antagonist Ketanserin endothelin receptor antagonist Bosentan, Ambrisentan, Sitaxsentan MAOI Pargyline THI Metirosine Diuretics Low ceiling Thiazides at DCT Bendroflumethiazide Hydroflumethiazide Hydrochlorothiazide Chlorothiazide Polythiazide Trichlormethiazide Cyclopenthiazide Methyclothiazide Cyclothiazide Mebutizide Sulfonamides Quinethazone Clopamide Chlortalidone Mefruside Clofenamide Metolazone Meticrane Xipamide Indapamide Clorexolone Fenquizone Other Mersalyl Theobromine Cicletanine osmotic Mannitol, Urea carbonic anhydrase inhibitor at PT Acetazolamide High ceiling Loop diuretic at AL Bumetanide, Furosemide, Torasemide, Ethacrynic acid Potassium-sparing at CD ESC blockers Amiloride, Triamterene aldosterone antagonists Spironolactone, Eplerenone, Potassium canrenoate, Canrenone Retrieved from http://en..org/wiki/Loop_diuretic Categories: Loop diureticsHidden category: Articles needing additional references from August 2008 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Español Français Polski Português This page was last modified on 16 August 2008, at 04:05
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