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badge-goodarticle mw-list-item" title="good article badge"><a href="https://de.wikipedia.org/wiki/Schleifendiuretika" title="Schleifendiuretika – German" lang="de" hreflang="de" data-title="Schleifendiuretika" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Diur%C3%A9tico_del_asa" title="Diurético del asa – Spanish" lang="es" hreflang="es" data-title="Diurético del asa" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-eu mw-list-item"><a href="https://eu.wikipedia.org/wiki/Henle-lakioko_diuretiko" title="Henle-lakioko diuretiko – Basque" lang="eu" hreflang="eu" data-title="Henle-lakioko diuretiko" data-language-autonym="Euskara" data-language-local-name="Basque" class="interlanguage-link-target"><span>Euskara</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%AF%DB%8C%D9%88%D8%B1%D8%AA%DB%8C%DA%A9_%D9%82%D9%88%D8%B3_%D9%87%D9%86%D9%84%D9%87" title="دیورتیک قوس هنله – Persian" lang="fa" hreflang="fa" data-title="دیورتیک قوس هنله" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Diur%C3%A9tique_de_l%27anse" title="Diurétique de l'anse – French" lang="fr" hreflang="fr" data-title="Diurétique de l'anse" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/%EA%B3%A0%EB%A6%AC_%EC%9D%B4%EB%87%A8%EC%A0%9C" title="고리 이뇨제 – Korean" lang="ko" hreflang="ko" data-title="고리 이뇨제" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target"><span>한국어</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Diuretici_dell%27ansa" title="Diuretici dell'ansa – Italian" lang="it" hreflang="it" data-title="Diuretici dell'ansa" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-he mw-list-item"><a href="https://he.wikipedia.org/wiki/%D7%9E%D7%A9%D7%AA%D7%9F_%D7%9C%D7%95%D7%9C%D7%90%D7%94" title="משתן לולאה – Hebrew" lang="he" hreflang="he" data-title="משתן לולאה" data-language-autonym="עברית" data-language-local-name="Hebrew" class="interlanguage-link-target"><span>עברית</span></a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/Lisdiuretica" title="Lisdiuretica – Dutch" 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<div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Diuretics that act along the loop of Henle in the kidneys</div> <style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><table class="infobox"><tbody><tr><th colspan="2" class="infobox-above" style="background-color: #ddbbee">Loop diuretic</th></tr><tr><td colspan="2" class="infobox-subheader"><i><a href="/wiki/Drug_class" title="Drug class">Drug class</a></i></td></tr><tr><td colspan="2" class="infobox-image"><span class="mw-default-size skin-invert-image" typeof="mw:File/Frameless"><a href="/wiki/File:Loop_diuretics.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/9/93/Loop_diuretics.svg/280px-Loop_diuretics.svg.png" decoding="async" width="280" height="175" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/93/Loop_diuretics.svg/420px-Loop_diuretics.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/93/Loop_diuretics.svg/560px-Loop_diuretics.svg.png 2x" data-file-width="1221" data-file-height="762" /></a></span><div class="infobox-caption">Structure of the loop diuretics Furosemide, Azosemide, Bumetanide, Piretanide, Torasemide, Ethacrynic acid and Etozolin</div></td></tr><tr><th colspan="2" class="infobox-header" style="background: #e8e8e8;">Class identifiers</th></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Synonym" title="Synonym">Synonyms</a></th><td class="infobox-data">High-ceiling diuretic<sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label">Use</th><td class="infobox-data"><a href="/wiki/Congestive_heart_failure" class="mw-redirect" title="Congestive heart failure">congestive heart failure</a>, <a href="/wiki/Nephrotic_syndrome" title="Nephrotic syndrome">nephrotic syndrome</a>, <a href="/wiki/Cirrhosis" title="Cirrhosis">cirrhosis</a>, <a href="/wiki/Hypertension" title="Hypertension">hypertension</a>, <a href="/wiki/Edema" title="Edema">edema</a><sup id="cite_ref-1" class="reference"><a href="#cite_note-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Anatomical_Therapeutic_Chemical_Classification_System" title="Anatomical Therapeutic Chemical Classification System">ATC code</a></th><td class="infobox-data"><a href="/wiki/ATC_code_C03C" class="mw-redirect" title="ATC code C03C">C03C</a></td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Biological_target" title="Biological target">Biological target</a></th><td class="infobox-data"><a href="/wiki/Na-K-Cl_cotransporter" class="mw-redirect" title="Na-K-Cl cotransporter">Na-K-Cl cotransporter</a><sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup></td></tr><tr><th colspan="2" class="infobox-header" style="background: #e8e8e8;">External links</th></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Medical_Subject_Headings" title="Medical Subject Headings">MeSH</a></th><td class="infobox-data"><span class="reflink plainlinks nourlexpansion"><a rel="nofollow" class="external text" href="https://meshb.nlm.nih.gov/record/ui?ui=D049994">D049994</a></span></td></tr><tr><th colspan="2" class="infobox-header" style="background: #e8e8e8;">Legal status</th></tr><tr><td colspan="2" class="infobox-below" style="background: #e8e8e8; text-align: center"><a href="https://www.wikidata.org/wiki/Q424280" class="extiw" title="d:Q424280">In Wikidata</a></td></tr></tbody></table> <p><b>Loop diuretics</b> are pharmacological agents that primarily inhibit the <a href="/wiki/Na-K-Cl_cotransporter" class="mw-redirect" title="Na-K-Cl cotransporter">Na-K-Cl cotransporter</a> located on the luminal membrane of cells along the <a href="/wiki/Thick_ascending_limb_of_the_loop_of_Henle" class="mw-redirect" title="Thick ascending limb of the loop of Henle">thick ascending limb of the loop of Henle</a>.<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> They are often used for the treatment of <a href="/wiki/Hypertension" title="Hypertension">hypertension</a> and <a href="/wiki/Edema" title="Edema">edema</a> secondary to <a href="/wiki/Congestive_heart_failure" class="mw-redirect" title="Congestive heart failure">congestive heart failure</a>, <a href="/wiki/Liver_cirrhosis" class="mw-redirect" title="Liver cirrhosis">liver cirrhosis</a>, or <a href="/wiki/Chronic_kidney_disease" title="Chronic kidney disease">chronic kidney disease</a>. While <a href="/wiki/Thiazide" title="Thiazide">thiazide</a> diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Mechanism_of_action">Mechanism of action</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Loop_diuretic&action=edit&section=1" title="Edit section: Mechanism of action"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Loop diuretics are 90% bonded to proteins and are secreted into the <a href="/wiki/Proximal_convoluted_tubule" class="mw-redirect" title="Proximal convoluted tubule">proximal convoluted tubule</a> through <a href="/wiki/Organic_anion_transporter_1" title="Organic anion transporter 1">organic anion transporter 1</a> (OAT-1), OAT-2, and <a href="/wiki/ABCC4" title="ABCC4">ABCC4</a>. Loop diuretics act on the <a href="/wiki/Na-K-2Cl_symporter" class="mw-redirect" title="Na-K-2Cl symporter">Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>−</sup> symporter</a> (NKCC2) in the thick ascending limb of the <a href="/wiki/Loop_of_Henle" title="Loop of Henle">loop of Henle</a> to inhibit sodium, chloride and potassium reabsorption. This is achieved by competing for the Cl<sup>−</sup> binding site. Loop diuretics also inhibit NKCC2 at <a href="/wiki/Macula_densa" title="Macula densa">macula densa</a>, reducing sodium transported into macula densa cells. This stimulates the release of <a href="/wiki/Renin" title="Renin">renin</a>, which through <a href="/wiki/Renin%E2%80%93angiotensin_system" title="Renin–angiotensin system">renin–angiotensin system</a>, increases fluid retention in the body, increases the perfusion of <a href="/wiki/Glomerulus_(kidney)" title="Glomerulus (kidney)">glomerulus</a>, thus increasing <a href="/wiki/Glomerular_filtration_rate" title="Glomerular filtration rate">glomerular filtration rate</a> (GFR). At the same time, loop diuretics inhibit the <a href="/wiki/Tubuloglomerular_feedback" title="Tubuloglomerular feedback">tubuloglomerular feedback</a> mechanism so that increase in salts at the lumen near macula densa does not trigger a response that reduces the GFR.<sup id="cite_ref-NEJM_2017_6-0" class="reference"><a href="#cite_note-NEJM_2017-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>Loop diuretics also inhibit <a href="/wiki/Magnesium" title="Magnesium">magnesium</a> and <a href="/wiki/Calcium" title="Calcium">calcium</a> reabsorption in the thick ascending limb. Absorption of magnesium and calcium are dependent upon the positive voltage at the luminal side and less positive voltage at the interstitial side with transepithelial voltage gradient of 10 mV. This causes the magnesium and calcium ions to be repelled from luminal side to interstitial side, promoting their absorption. The difference in voltage in both sides is set up by potassium recycling through <a href="/wiki/ROMK" title="ROMK">renal outer medullary potassium channel</a>. By inhibiting the potassium recycling, the voltage gradient is abolished and magnesium and calcium reabsorption are inhibited.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> By disrupting the reabsorption of these ions, loop diuretics prevent the generation of a <a href="/wiki/Tonicity#Hypertonic_solution" title="Tonicity">hypertonic</a> <a href="/wiki/Renal_medulla" title="Renal medulla">renal medulla</a>. Without such a concentrated medulla, water has less of an <a href="/wiki/Osmotic_pressure" title="Osmotic pressure">osmotic</a> driving force to leave the <a href="/wiki/Collecting_duct_system" title="Collecting duct system">collecting duct system</a>, ultimately resulting in increased <a href="/wiki/Urine" title="Urine">urine</a> 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.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (August 2024)">citation needed</span></a></i>]</sup> </p><p>A secondary effect of loop diuretics is to increase the production of <a href="/wiki/Prostaglandins" class="mw-redirect" title="Prostaglandins">prostaglandins</a>, which results in vasodilation and increased blood supply to the kidney.<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> Prostaglandin-mediated <a href="/wiki/Vasodilation" title="Vasodilation">vasodilation</a> of preglomerular <a href="/wiki/Afferent_arterioles" title="Afferent arterioles">afferent arterioles</a> increases the <a href="/wiki/Glomerular_filtration_rate" title="Glomerular filtration rate">glomerular filtration rate</a> (GFR) and facilitates diuresis. The collective effects of decreased blood volume and vasodilation help decrease blood pressure and ameliorate <a href="/wiki/Edema" title="Edema">edema</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (August 2024)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading2"><h2 id="Pharmacokinetics">Pharmacokinetics</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Loop_diuretic&action=edit&section=2" title="Edit section: Pharmacokinetics"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Loop diuretics are highly protein bound and therefore have a low volume of distribution. The protein bound nature of the loop diuretic molecules causes it to be secreted via several transporter molecules along the luminal wall of the proximal convoluted tubules to be able to exert its function.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (August 2024)">citation needed</span></a></i>]</sup> </p><p>Loop diuretics usually have a ceiling effect whereby doses greater than a certain maximum amount will not increase the clinical effect of the drug. Also, there is a threshold minimum concentration of loop diuretics that needs to be achieved at the thick ascending limb to enable the onset of abrupt diuresis. <sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>The availability of <a href="/wiki/Furosemide" title="Furosemide">furosemide</a> is highly variable, ranging from 10% to 90%. The <a href="/wiki/Biological_half-life" title="Biological half-life">biological half-life</a> of furosemide is limited by <a href="/wiki/Absorption_(pharmacology)" title="Absorption (pharmacology)">absorption</a> from the <a href="/wiki/Gastrointestinal_tract" title="Gastrointestinal tract">gastrointestinal tract</a> into the bloodstream. The apparent half-life of its excretion is higher than the apparent half-life of absorption via the oral route. Therefore, furosemide taken intravenously is twice as potent as an equivalent dose taken orally.<sup id="cite_ref-NEJM_2017_6-1" class="reference"><a href="#cite_note-NEJM_2017-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>However, for torsemide and bumetanide, their oral bioavailability is consistently higher than 90%. Torsemide has a longer half life in heart failure patients (6<span class="nowrap"> </span>hours) than furosemide (2.7<span class="nowrap"> </span>hours). A 40<span class="nowrap"> </span>mg dose of furosemide is clinically equivalent to a 20<span class="nowrap"> </span>mg dose of torsemide and to a 1<span class="nowrap"> </span>mg dose of bumetanide.<sup id="cite_ref-NEJM_2017_6-2" class="reference"><a href="#cite_note-NEJM_2017-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Clinical_use">Clinical use</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Loop_diuretic&action=edit&section=3" title="Edit section: Clinical use"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Loop diuretics are principally used in the following indications: </p> <ul><li><a href="/wiki/Heart_failure" title="Heart failure">Heart failure</a> - Giving 2.5 times of previous oral dose twice daily for those with <a href="/wiki/Acute_decompensated_heart_failure" title="Acute decompensated heart failure">acute decompensated heart failure</a> is a reasonable strategy. However, daily assessment of clinical response is needed to adjust the subsequent doses.<sup id="cite_ref-NEJM_2017_6-3" class="reference"><a href="#cite_note-NEJM_2017-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Edema" title="Edema">Edema</a> - Volume overload associated with liver <a href="/wiki/Cirrhosis" title="Cirrhosis">cirrhosis</a>, <a href="/wiki/Heart_failure" title="Heart failure">heart failure</a>, or <a href="/wiki/Nephrotic_syndrome" title="Nephrotic syndrome">nephrotic syndrome</a><sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Cerebral_edema" title="Cerebral edema">Cerebral edema</a> - intravenous furosemide can be combined with <a href="/wiki/Mannitol" title="Mannitol">mannitol</a> to initiate rapid diuresis. However, the optimum duration of such treatment remains unknown. Frequent fluid status monitoring is required to prevent intravascular volume depletion which leads to reduced cerebral perfusion. A bolus intravenous dose of 10 or 20 mg of furosemide can be administered and then followed by intravenous bolus of 2 or 3% hypertonic saline to increase the serum sodium level.<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Pulmonary_edema" title="Pulmonary edema">Pulmonary edema</a> - Slow intravenous bolus dose of 40 to 80 mg furosemide at 4 mg per minute is indicated for patients with fluid overload and pulmonary edema. Such dose can be repeated after 20 minutes. After the bolus, a continuous intravenous infusion can be given at 5 to 10 mg per hour. For those with underlying <a href="/wiki/Renal_impairment" class="mw-redirect" title="Renal impairment">renal impairment</a> or severe heart failure, up to 160 to 200 mg bolus dose can be given.<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup></li> <li><a href="/wiki/Hypertension" title="Hypertension">Hypertension</a> - A systematic review by the Cochrane Hypertension group assessing the anti-hypertensive effects of loop diuretics found only a modest reduction in blood pressure when compared to placebo.<sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> According to Joint National Committee (JNC-8) guidelines, the first line treatment of hypertension is <a href="/wiki/Thiazide" title="Thiazide">thiazide</a> diuretics. The use of loop diuretics is not mentioned in this guideline. Meanwhile, according to 2013 European Society of Cardiology (ESC) guidelines, a loop diuretic can only replace thiazide-type diuretics if there is renal impairment (<a href="/wiki/Creatinine" title="Creatinine">Creatinine</a> of more than 1.5 mg/dL or estimated <a href="/wiki/Glomerular_filtration_rate" title="Glomerular filtration rate">glomerular filtration rate</a> (eGFR) of less 30 mL/min/1.73 m<sup>2</sup> due to lack of long term cardiovascular outcome data and appropriate dosing regimen of its use.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup></li></ul> <p>The 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guidelines stated that diuretics should not be used to treat acute kidney injury, except for the management of volume overload. Diuretics has not shown any benefits of preventing or treating acute kidney injury.<sup id="cite_ref-Claire_2013_16-0" class="reference"><a href="#cite_note-Claire_2013-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p><p>They are also sometimes used in the management of severe <a href="/wiki/Hypercalcemia" class="mw-redirect" title="Hypercalcemia">hypercalcemia</a> in combination with adequate rehydration.<sup id="cite_ref-AMH2004_17-0" class="reference"><a href="#cite_note-AMH2004-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Resistance">Resistance</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Loop_diuretic&action=edit&section=4" title="Edit section: Resistance"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Diuretic resistance is defined as failure of diuretics to reduce fluid retention (can be measured by low urinary sodium) despite using the maximal dose of drugs. There are various causes for the resistance towards loop diuretics. After initial period of diuresis, there will be a period of "post-diuretic sodium retention" where the rate of sodium excretion does not reach as much as the initial diuresis period. Increase intake of sodium during this period will offset the amount of excreted sodium, and thus causing diuretic resistance. Prolonged usage of loop diuretics will also contributes to resistance through "braking phenomenon". This is the body physiological response to reduced extracellular fluid volume, where renin-angiotensin-aldosterone system will be activated which results in nephron remodelling. Nephron remodeling increases the number of distal convoluted cells, principle cells, and intercalated cells. These cells have <a href="/wiki/Sodium-chloride_symporter" title="Sodium-chloride symporter">sodium-chloride symporter</a> at distal convoluted tubule, epithelial sodium channels, and chloride-bicarbonate exchanger pendrin. This will promote sodium reabsorption and fluid retention, causing diuretic resistance. Other factors includes gut edema which slows down the absorption of oral loop diuretics. <a href="/wiki/Chronic_kidney_disease" title="Chronic kidney disease">Chronic kidney disease</a> (CKD) reduces renal flow rate, reducing the delivery of diuretic molecules into the nephron, limiting sodium excretion and increasing sodium retention, causing diuretic resistance. <a href="/wiki/Non-steroidal_anti-inflammatory_drug" class="mw-redirect" title="Non-steroidal anti-inflammatory drug">Non-steroidal anti-inflammatory drug</a> (NSAID) can compete with loop diuretics for organic ion transporters, thus preventing the diuretic molecules from being secreted into the proximal convoluted tubules.<sup id="cite_ref-NEJM_2017_6-4" class="reference"><a href="#cite_note-NEJM_2017-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>Those with diuretic resistance, cardiorenal syndrome, and severe right ventricular dysfunction may have better response to continuous diuretic infusion. Diuretic dosages is adjusted to produce 3 to 5 litres of urine per day. <a href="/wiki/Thiazide" title="Thiazide">Thiazide</a> (blockade of sodium-chloride symporter), <a href="/wiki/Amiloride" title="Amiloride">amiloride</a> (blockade of epithelial sodium channels) and <a href="/wiki/Carbonic_anhydrase_inhibitor" title="Carbonic anhydrase inhibitor">carbonic anhydrase inhibitors</a> (blockade of chloride-bicarbonate exchanger pendrin) has been suggested to complement the action of loop diuretics in resistance cases but limited evidence are available to support their use.<sup id="cite_ref-NEJM_2017_6-5" class="reference"><a href="#cite_note-NEJM_2017-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Adverse_effects">Adverse effects</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Loop_diuretic&action=edit&section=5" title="Edit section: Adverse effects"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The most common adverse drug reactions (ADRs) are dose-related and arise from the effect of loop diuretics on diuresis and <a href="/wiki/Electrolyte" title="Electrolyte">electrolyte</a> balance.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (August 2024)">citation needed</span></a></i>]</sup> </p><p>Common ADRs include: <a href="/wiki/Hyponatremia" title="Hyponatremia">hyponatremia</a>, <a href="/wiki/Hypokalemia" title="Hypokalemia">hypokalemia</a>, <a href="/wiki/Hypomagnesemia" class="mw-redirect" title="Hypomagnesemia">hypomagnesemia</a>, <a href="/wiki/Dehydration" title="Dehydration">dehydration</a>, <a href="/wiki/Hyperuricemia" title="Hyperuricemia">hyperuricemia</a>, <a href="/wiki/Gout" title="Gout">gout</a>, <a href="/wiki/Dizziness" title="Dizziness">dizziness</a>, <a href="/wiki/Postural_hypotension" class="mw-redirect" title="Postural hypotension">postural hypotension</a>, <a href="/wiki/Fainting" class="mw-redirect" title="Fainting">syncope</a>.<sup id="cite_ref-AMH2004_17-1" class="reference"><a href="#cite_note-AMH2004-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> The loss of magnesium as a result of loop diuretics has also been suggested as a possible cause of pseudogout (<a href="/wiki/Chondrocalcinosis" title="Chondrocalcinosis">chondrocalcinosis</a>).<sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> </p><p>Infrequent ADRs include: <a href="/wiki/Dyslipidemia" title="Dyslipidemia">dyslipidemia</a>, increased serum <a href="/wiki/Creatinine" title="Creatinine">creatinine</a> concentration, hypocalcemia, <a href="/wiki/Rash" title="Rash">rash</a>. <a href="/wiki/Metabolic_alkalosis" title="Metabolic alkalosis">Metabolic alkalosis</a> may also be seen with loop diuretic use.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (August 2024)">citation needed</span></a></i>]</sup> </p><p><a href="/wiki/Ototoxicity" title="Ototoxicity">Ototoxicity</a> (damage to the inner ear) is a serious, but rare ADR associated with use of loop diuretics. This may be limited to <a href="/wiki/Tinnitus" title="Tinnitus">tinnitus</a> and <a href="/wiki/Vertigo_(medical)" class="mw-redirect" title="Vertigo (medical)">vertigo</a>, but may result in <a href="/wiki/Deafness" title="Deafness">deafness</a> in serious cases.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (August 2024)">citation needed</span></a></i>]</sup> </p><p>Loop diuretics may also precipitate kidney failure in patients concurrently taking an <a href="/wiki/NSAID" class="mw-redirect" title="NSAID">NSAID</a> and an <a href="/wiki/ACE_inhibitor" title="ACE inhibitor">ACE inhibitor</a>—the so-called "triple whammy" effect.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p><p>Because furosemide, <a href="/wiki/Torsemide" class="mw-redirect" title="Torsemide">torsemide</a> and <a href="/wiki/Bumetanide" title="Bumetanide">bumetanide</a> are technically <a href="/wiki/Sulfa" class="mw-redirect" title="Sulfa">sulfa</a> drugs, there is a theoretical risk that patients sensitive to <a href="/wiki/Sulfonamide_(medicine)" title="Sulfonamide (medicine)">sulfonamides</a> may be sensitive to these loop diuretics. This risk is stated on drug packaging inserts. However, the actual risk of crossreactivity is largely unknown and there are some sources that dispute the existence of such cross reactivity.<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> In one study it was found that only 10% of patients with allergy to antibiotic sulfonamides were also allergic to diuretic sulfonamides, but it is unclear if this represents true cross reactivity or the nature of being prone to allergy.<sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> </p><p><a href="/wiki/Ethacrynic_acid" class="mw-redirect" title="Ethacrynic acid">Ethacrynic acid</a> is the only medication of this class that is not a sulfonamide. It carries a greater risk of reversible or permanent hearing loss (ototoxicity),<sup id="cite_ref-pmid7446061_23-0" class="reference"><a href="#cite_note-pmid7446061-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> and has a distinct complication of being associated with gastrointestinal toxicity.<sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Examples">Examples</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Loop_diuretic&action=edit&section=6" title="Edit section: Examples"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Furosemide" title="Furosemide">Furosemide</a></li> <li><a href="/wiki/Bumetanide" title="Bumetanide">Bumetanide</a></li> <li><a href="/wiki/Ethacrynic_acid" class="mw-redirect" title="Ethacrynic acid">Ethacrynic acid</a></li> <li><a href="/wiki/Torasemide" title="Torasemide">Torasemide</a></li></ul> <table class="wikitable"> <tbody><tr> <th>Loop Diuretic</th> <th>Relative Potency<sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> </th></tr> <tr> <td>Furosemide</td> <td>40 mg </td></tr> <tr> <td>Torasemide</td> <td>20 mg </td></tr> <tr> <td>Ethacrynic Acid</td> <td>50 mg </td></tr> <tr> <td>Bumetanide</td> <td>1 mg </td></tr></tbody></table> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Loop_diuretic&action=edit&section=7" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist"> <div class="mw-references-wrap mw-references-columns"><ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output 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title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Kidney+International&rft.atitle=Diuretics.&rft.volume=39&rft.issue=2&rft.pages=%3Cspan+class%3D%22nowrap%22%3E336-%3C%2Fspan%3E52&rft.date=1991-02&rft_id=info%3Adoi%2F10.1038%2Fki.1991.43&rft_id=info%3Apmid%2F2002648&rft.aulast=Rose&rft.aufirst=BD&rft_id=https%3A%2F%2Fdoi.org%2F10.1038%252Fki.1991.43&rfr_id=info%3Asid%2Fen.wikipedia.org%3ALoop+diuretic" class="Z3988"></span></span> </li> <li id="cite_note-8"><span class="mw-cite-backlink"><b><a href="#cite_ref-8">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222" /><cite id="CITEREFLiguoriA._CasiniM._Di_LoretoI._Andreini1999" class="citation journal cs1">Liguori, A.; A. 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"The nature of the ototoxic actions of ethacrynic acid upon the mammalian endolymph system. I. Functional aspects". <i>Acta Oto-Laryngologica</i>. <b>89</b> (<span class="nowrap">5–</span>6): <span class="nowrap">407–</span>18. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.3109%2F00016488009127156">10.3109/00016488009127156</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/7446061">7446061</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Acta+Oto-Laryngologica&rft.atitle=The+nature+of+the+ototoxic+actions+of+ethacrynic+acid+upon+the+mammalian+endolymph+system.+I.+Functional+aspects&rft.volume=89&rft.issue=%3Cspan+class%3D%22nowrap%22%3E5%E2%80%93%3C%2Fspan%3E6&rft.pages=%3Cspan+class%3D%22nowrap%22%3E407-%3C%2Fspan%3E18&rft.date=1980&rft_id=info%3Adoi%2F10.3109%2F00016488009127156&rft_id=info%3Apmid%2F7446061&rft.aulast=Bosher&rft.aufirst=SK&rfr_id=info%3Asid%2Fen.wikipedia.org%3ALoop+diuretic" class="Z3988"></span></span> </li> <li id="cite_note-24"><span class="mw-cite-backlink"><b><a href="#cite_ref-24">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222" /><cite id="CITEREFLaraghPaul_J._CannonWilliam_B._StasonHenry_O._Heinemann1966" class="citation journal cs1">Laragh, John H.; Paul J. Cannon; William B. Stason; Henry O. Heinemann (1966). "Physiologic and Clinical Observations on Furosemide and Ethacrynic Acid*". <i>Annals of the New York Academy of Sciences</i>. <b>139</b> (2): <span class="nowrap">453–</span>465. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/1966NYASA.139..453L">1966NYASA.139..453L</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1111%2Fj.1749-6632.1966.tb41219.x">10.1111/j.1749-6632.1966.tb41219.x</a>. <a href="/wiki/ISSN_(identifier)" class="mw-redirect" title="ISSN (identifier)">ISSN</a> <a rel="nofollow" class="external text" href="https://search.worldcat.org/issn/1749-6632">1749-6632</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/5339515">5339515</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:6942431">6942431</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Physiologic+and+Clinical+Observations+on+Furosemide+and+Ethacrynic+Acid%2A&rft.volume=139&rft.issue=2&rft.pages=%3Cspan+class%3D%22nowrap%22%3E453-%3C%2Fspan%3E465&rft.date=1966&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A6942431%23id-name%3DS2CID&rft_id=info%3Abibcode%2F1966NYASA.139..453L&rft.issn=1749-6632&rft_id=info%3Adoi%2F10.1111%2Fj.1749-6632.1966.tb41219.x&rft_id=info%3Apmid%2F5339515&rft.aulast=Laragh&rft.aufirst=John+H.&rft.au=Paul+J.+Cannon&rft.au=William+B.+Stason&rft.au=Henry+O.+Heinemann&rfr_id=info%3Asid%2Fen.wikipedia.org%3ALoop+diuretic" class="Z3988"></span></span> </li> <li id="cite_note-25"><span class="mw-cite-backlink"><b><a href="#cite_ref-25">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222" /><cite id="CITEREFBruntonKnollmann2023" class="citation book cs1">Brunton, Laurence; Knollmann, Bjorn (2023). <i>Goodman & Gilman's the pharmacological basis of therapeutics</i> (Fourteenth ed.). New York Chicago San Francisco: McGraw Hill. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-1264258079" title="Special:BookSources/978-1264258079"><bdi>978-1264258079</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Goodman+%26+Gilman%27s+the+pharmacological+basis+of+therapeutics&rft.place=New+York+Chicago+San+Francisco&rft.edition=Fourteenth&rft.pub=McGraw+Hill&rft.date=2023&rft.isbn=978-1264258079&rft.aulast=Brunton&rft.aufirst=Laurence&rft.au=Knollmann%2C+Bjorn&rfr_id=info%3Asid%2Fen.wikipedia.org%3ALoop+diuretic" class="Z3988"></span></span> </li> </ol></div></div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Loop_diuretic&action=edit&section=8" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a rel="nofollow" class="external text" href="http://www.fpnotebook.com/cv/pharm/lpdrtc.htm">Loop Diuretic</a>, from the Family Practice Notebook</li></ul> <div class="navbox-styles"><style data-mw-deduplicate="TemplateStyles:r1129693374">.mw-parser-output .hlist dl,.mw-parser-output .hlist ol,.mw-parser-output .hlist ul{margin:0;padding:0}.mw-parser-output .hlist dd,.mw-parser-output .hlist dt,.mw-parser-output .hlist li{margin:0;display:inline}.mw-parser-output .hlist.inline,.mw-parser-output .hlist.inline dl,.mw-parser-output .hlist.inline ol,.mw-parser-output .hlist.inline ul,.mw-parser-output .hlist dl dl,.mw-parser-output .hlist dl ol,.mw-parser-output .hlist dl ul,.mw-parser-output .hlist ol dl,.mw-parser-output .hlist ol ol,.mw-parser-output .hlist ol ul,.mw-parser-output .hlist ul dl,.mw-parser-output .hlist ul ol,.mw-parser-output .hlist ul ul{display:inline}.mw-parser-output .hlist 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aria-labelledby="Diuretics_(C03)758" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374" /><style data-mw-deduplicate="TemplateStyles:r1239400231">.mw-parser-output .navbar{display:inline;font-size:88%;font-weight:normal}.mw-parser-output .navbar-collapse{float:left;text-align:left}.mw-parser-output .navbar-boxtext{word-spacing:0}.mw-parser-output .navbar ul{display:inline-block;white-space:nowrap;line-height:inherit}.mw-parser-output .navbar-brackets::before{margin-right:-0.125em;content:"[ "}.mw-parser-output .navbar-brackets::after{margin-left:-0.125em;content:" ]"}.mw-parser-output .navbar li{word-spacing:-0.125em}.mw-parser-output .navbar a>span,.mw-parser-output .navbar a>abbr{text-decoration:inherit}.mw-parser-output .navbar-mini abbr{font-variant:small-caps;border-bottom:none;text-decoration:none;cursor:inherit}.mw-parser-output .navbar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{font-size:114%;margin:0 4em}html.skin-theme-clientpref-night .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}@media(prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .navbar li a abbr{color:var(--color-base)!important}}@media print{.mw-parser-output .navbar{display:none!important}}</style><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Diuretics" title="Template:Diuretics"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Diuretics" title="Template talk:Diuretics"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Diuretics" title="Special:EditPage/Template:Diuretics"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Diuretics_(C03)758" style="font-size:114%;margin:0 4em"><a href="/wiki/Diuretic" title="Diuretic">Diuretics</a> (<a href="/wiki/ATC_code_C03" title="ATC code C03">C03</a>)</div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Sulfonamide_(medicine)" title="Sulfonamide (medicine)">Sulfonamides</a><br />(and <a href="/wiki/Etacrynic_acid" title="Etacrynic acid">etacrynic acid</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Carbonic_anhydrase_inhibitor" title="Carbonic anhydrase inhibitor">CA inhibitors</a> (at <a href="/wiki/Proximal_tubule" title="Proximal tubule">PT</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Acetazolamide" title="Acetazolamide">Acetazolamide</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a class="mw-selflink selflink">Loop</a> (<a href="/wiki/Na-K-Cl_cotransporter" class="mw-redirect" title="Na-K-Cl cotransporter">Na-K-Cl</a> at <a href="/wiki/Thick_ascending_limb_of_loop_of_Henle" class="mw-redirect" title="Thick ascending limb of loop of Henle">AL</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Furosemide" title="Furosemide">Furosemide</a><sup>#</sup></li> <li><a href="/wiki/Azosemide" title="Azosemide">Azosemide</a></li> <li><a href="/wiki/Bumetanide" title="Bumetanide">Bumetanide</a></li> <li><a href="/wiki/Etacrynic_acid" title="Etacrynic acid">Etacrynic acid</a></li> <li><a href="/wiki/Etozolin" title="Etozolin">Etozolin</a></li> <li><a href="/wiki/Indacrinone" title="Indacrinone">Indacrinone</a></li> <li><a href="/wiki/Muzolimine" title="Muzolimine">Muzolimine</a></li> <li><a href="/wiki/Ozolinone" title="Ozolinone">Ozolinone</a></li> <li><a href="/wiki/Piretanide" title="Piretanide">Piretanide</a></li> <li><a href="/wiki/Tienilic_acid" title="Tienilic acid">Tienilic acid</a><sup>‡</sup></li> <li><a href="/wiki/Torasemide" title="Torasemide">Torasemide</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Thiazide" title="Thiazide">Thiazides</a> (<a href="/wiki/Sodium-chloride_symporter" title="Sodium-chloride symporter">Na-Cl</a> at <a href="/wiki/Distal_convoluted_tubule" title="Distal convoluted tubule">DCT</a>,<br /><a href="/wiki/Diuretic#Calcium-sparing_diuretics" title="Diuretic">Calcium-sparing</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Altizide" title="Altizide">Altizide</a></li> <li><a href="/wiki/Bendroflumethiazide" title="Bendroflumethiazide">Bendroflumethiazide</a></li> <li><a href="/wiki/Butizide" title="Butizide">Butizide</a></li> <li><a href="/wiki/Chlorothiazide" title="Chlorothiazide">Chlorothiazide</a></li> <li><a href="/wiki/Cyclopenthiazide" title="Cyclopenthiazide">Cyclopenthiazide</a></li> <li><a href="/wiki/Cyclothiazide" title="Cyclothiazide">Cyclothiazide</a></li> <li><a href="/wiki/Epitizide" title="Epitizide">Epitizide</a></li> <li><a href="/wiki/Hydrochlorothiazide" title="Hydrochlorothiazide">Hydrochlorothiazide</a></li> <li><a href="/wiki/Hydroflumethiazide" title="Hydroflumethiazide">Hydroflumethiazide</a></li> <li><a href="/wiki/Mebutizide" title="Mebutizide">Mebutizide</a></li> <li><a href="/wiki/Methyclothiazide" title="Methyclothiazide">Methyclothiazide</a></li> <li><a href="/wiki/Polythiazide" title="Polythiazide">Polythiazide</a></li> <li><a href="/wiki/Trichlormethiazide" title="Trichlormethiazide">Trichlormethiazide</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Thiazide-like_diuretic" title="Thiazide-like diuretic">Thiazide-likes</a> (primarily <a href="/wiki/Distal_convoluted_tubule" title="Distal convoluted tubule">DCT</a>)</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Chlortalidone" title="Chlortalidone">Chlortalidone</a></li> <li><a href="/wiki/Clofenamide" title="Clofenamide">Clofenamide</a></li> <li><a href="/wiki/Clopamide" title="Clopamide">Clopamide</a></li> <li><a href="/wiki/Clorexolone" title="Clorexolone">Clorexolone</a></li> <li><a href="/wiki/Fenquizone" title="Fenquizone">Fenquizone</a></li> <li><a href="/wiki/Indapamide" title="Indapamide">Indapamide</a></li> <li><a href="/wiki/Mefruside" title="Mefruside">Mefruside</a></li> <li><a href="/wiki/Meticrane" title="Meticrane">Meticrane</a></li> <li><a href="/wiki/Metolazone" title="Metolazone">Metolazone</a></li> <li><a href="/wiki/Quinethazone" title="Quinethazone">Quinethazone</a></li> <li><a href="/wiki/Xipamide" title="Xipamide">Xipamide</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Potassium-sparing_diuretic" title="Potassium-sparing diuretic">Potassium-sparing</a> (at <a href="/wiki/Collecting_duct_system" title="Collecting duct system">CD</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Epithelial_sodium_channel_blocker" title="Epithelial sodium channel blocker">ESC blockers</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Amiloride" title="Amiloride">Amiloride</a><sup>#</sup></li> <li><a href="/wiki/Benzamil" title="Benzamil">Benzamil</a></li> <li><a href="/wiki/Triamterene" title="Triamterene">Triamterene</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Antimineralocorticoid" class="mw-redirect" title="Antimineralocorticoid">Aldosterone antagonists</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Spirolactone" title="Spirolactone">Spirolactones</a></i> <ul><li><a href="/wiki/Spironolactone" title="Spironolactone">Spironolactone</a><sup>#</sup></li> <li><a href="/wiki/Canrenone" title="Canrenone">Canrenone</a></li> <li><a href="/wiki/Eplerenone" title="Eplerenone">Eplerenone</a></li> <li><a href="/wiki/Potassium_canrenoate" title="Potassium canrenoate">Potassium canrenoate</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Nonsteroidal" title="Nonsteroidal">Nonsteroidal</a></i> <ul><li><a href="/wiki/Finerenone" title="Finerenone">Finerenone</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Osmotic_diuretic" title="Osmotic diuretic">Osmotic diuretics</a> (<a href="/wiki/Proximal_tubule" title="Proximal tubule">PT</a>, <a href="/wiki/Descending_limb_of_loop_of_Henle" title="Descending limb of loop of Henle">DL</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Mannitol" title="Mannitol">Mannitol</a><sup>#</sup></li> <li><a href="/wiki/Glycerol" title="Glycerol">Glycerol</a></li> <li><a href="/wiki/Urea" title="Urea">Urea</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Vasopressin_receptor_antagonist" title="Vasopressin receptor antagonist">Vasopressin receptor inhibitors</a><br />(<a href="/wiki/Distal_convoluted_tubule" title="Distal convoluted tubule">DCT</a> and <a href="/wiki/Collecting_duct" class="mw-redirect" title="Collecting duct">CD</a>)</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i><a href="/wiki/Vasopressin_receptor_antagonist#Vaptans" title="Vasopressin receptor antagonist">Vaptans</a></i> <ul><li><a href="/wiki/Conivaptan" title="Conivaptan">Conivaptan</a></li> <li><a href="/wiki/Mozavaptan" title="Mozavaptan">Mozavaptan</a></li> <li><a href="/wiki/Satavaptan" title="Satavaptan">Satavaptan</a></li> <li><a href="/wiki/Tolvaptan" title="Tolvaptan">Tolvaptan</a></li></ul></li></ul> <ul><li><i><a href="/wiki/Vasopressin_receptor_antagonist#Demeclocycline_and_lithium" title="Vasopressin receptor antagonist">Others</a></i> <ul><li><a href="/wiki/Demeclocycline" title="Demeclocycline">Demeclocycline</a></li> <li><a href="/wiki/Lithium_carbonate" title="Lithium carbonate">Lithium carbonate</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Ethanol" title="Ethanol">Ethanol</a>, <a href="/wiki/Isopropanol" class="mw-redirect" title="Isopropanol">Isopropanol</a>, <a href="/wiki/Tert-Amyl_alcohol" title="Tert-Amyl alcohol">2M2B</a></li> <li><i><a href="/wiki/Mercurial_diuretic" title="Mercurial diuretic">mercurial diuretics</a></i> (<a href="/wiki/Chlormerodrin" title="Chlormerodrin">Chlormerodrin</a>, <a href="/wiki/Mersalyl" title="Mersalyl">Mersalyl</a>, <a href="/wiki/Meralluride" title="Meralluride">Meralluride</a>)</li> <li><a href="/wiki/Theobromine" title="Theobromine">Theobromine</a></li> <li><a href="/wiki/Cicletanine" title="Cicletanine">Cicletanine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Combination products</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Hydrochlorothiazide/triamterene" title="Hydrochlorothiazide/triamterene">Hydrochlorothiazide/triamterene</a></li></ul> </div></td></tr><tr><td class="navbox-abovebelow" colspan="2" style="padding: 0px;"><div><div class="hlist"> <ul><li><sup>#</sup><a href="/wiki/WHO_Model_List_of_Essential_Medicines" title="WHO Model List of Essential Medicines">WHO-EM</a></li> <li><sup>‡</sup><a href="/wiki/List_of_withdrawn_drugs" title="List of withdrawn drugs">Withdrawn</a> from market</li> <li><a href="/wiki/Clinical_trial" title="Clinical trial">Clinical trials</a>: <ul><li><sup>†</sup><a href="/wiki/Phases_of_clinical_research#Phase_III" title="Phases of clinical research">Phase III</a></li> <li><sup>§</sup>Never to phase III</li></ul></li></ul> 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