Diuretic 9078 225941691 2008-07-16T03:17:34Z Deor 3022076 Reverted edits by [[Special:Contributions/124.104.131.107|124.104.131.107]] ([[User talk:124.104.131.107|talk]]) to last version by 207.250.93.50 [[Image:Renal Diuretics.gif|thumb|300px|right|This illustration shows where some types of diuretics act, and what they do.]] A '''diuretic''' is any [[drug]] that elevates the rate of [[Urination|urination]] ([[diuresis]]). There are several categories of diuretics. All diuretics increase the excretion of water from the body, although each class of diuretic does so in a distinct way. == High ceiling loop diuretics == High ceiling diuretics are diuretics that may cause a substantial diuresis - up to 20%<ref>[http://www.thedrugmonitor.com/diuretics.html Drug Monitor - Diuretics]</ref> of the filtered load of [[sodium chloride|NaCl]] and water. This is huge, compared to that normal [[renal sodium reabsorption]] leaves only ~0.4% of filtered sodium in the urine. [[Loop diuretics]] have this ability, and are therefore often synonymous with high ceiling diuretics. Loop diuretics, such as [[furosemide]], inhibit the body's ability to reabsorb [[sodium]] at the ascending loop in the [[kidney]] which leads to a retention of water in the urine as water normally follows sodium back into the extracellular fluid (ECF). Other examples of high ceiling loop diuretics include [[ethacrynic acid]], [[torsemide]] and [[bumetanide]]. == Thiazides == Drugs such as [[hydrochlorothiazide]] act on the distal tubule and inhibit the [[Sodium-chloride symporter]] leading to a retention of water in the urine as water normally follows penetrating solutes. == Potassium-sparing diuretics == These are diuretics which do not promote the secretion of [[potassium]] into the urine; thus, potassium is spared and not lost as much as in other diuretics. Such drugs include [[spironolactone]] which is a [[competitive antagonist]] of [[aldosterone]]. [[Aldosterone]] normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal cells, preventing sodium reabsorption. Other examples of potassium-sparing diuretics are [[amiloride]], [[triamterene]] and [[potassium canreonate]]. == Osmotic diuretics == Compounds such as [[mannitol]] are filtered in the [[glomerulus]], but cannot be reabsorbed. Their presence leads to an increase in the osmolarity of the filtrate. To maintain osmotic balance, water is retained in the urine. ===High Blood Glucose=== [[Glucose]], like mannitol, is a sugar that can behave as an osmotic diuretic. Unlike mannitol, glucose is commonly found in the blood. However, in certain conditions such as [[diabetes mellitus]], the concentration of glucose in the blood exceeds the maximum resorption capacity of the kidney. When this happens, glucose remains in the filtrate, leading to the osmotic retention of water in the urine. Use of some [[drug]]s, especially [[stimulant]]s may also increase blood glucose and thus increase urination. == Uses == In [[medicine]], diuretics are used to treat [[heart failure]], [[liver cirrhosis]], [[hypertension]] and certain [[kidney disease]]s. Some diuretics, such as [[acetazolamide]], help to make the [[urine]] more [[alkaline]] and are helpful in increasing excretion of substances such as [[aspirin]] in cases of [[drug overdose|overdose]] or poisoning. Diuretics are often abused by sufferers of [[eating disorder]]s, especially [[bulimic]]s, in attempts at weight loss. The antihypertensive actions of some diuretics ([[thiazide]]s and [[loop diuretic]]s in particular) are independent of their diuretic effect. That is, the reduction in blood pressure is not due to decreased blood volume resulting from increased urine production, but occurs through other mechanisms and at lower doses than that required to produce diuresis. [[Indapamide]] was specifically designed with this in mind, and has a larger therapeutic window for hypertension (without pronounced diuresis) than most other diuretics. == Mechanism of action == Classification of common diuretics and their mechanisms of action: {| class="wikitable sortable" border="1" cellpadding="1" cellspacing="1" style="border-collapse: collapse; margin: 0 0 0 0.5em" |- align="center" style="border-bottom: 3px solid gray" ! bgcolor="#eeeeee" | Agent Group ! Examples ! bgcolor="#ddeeff" | Mechanism ! Location (numbered in distance along nephron) |- | bgcolor="#eeeeee" | ''' -''' | [[Ethanol]], [[Water]] | bgcolor="#ddeeff" | inhibits [[vasopressin]] secretion | 1. |- | bgcolor="#eeeeee" | '''Acidifying [[salt]]s''' | CaCl<sub>2</sub>, NH<sub>4</sub>Cl | bgcolor="#ddeeff" | | 1. |- | bgcolor="#eeeeee" | '''[[Arginine vasopressin receptor 2|Arginine&nbsp;vasopressin<br>receptor&nbsp;2]]&nbsp;antagonists''' | [[amphotericin B]], [[lithium citrate]] <!-- do these count ? - see [[Diabetes_Insipidus#Pathophysiology]] --> | bgcolor="#ddeeff" | inhibit vasopressin's action | 5. [[collecting duct]] |- | bgcolor="#eeeeee" | '''[[Aquaretics]]''' | [[Goldenrod]], [[Juniper]] | bgcolor="#ddeeff" | Increases blood flow in kidneys | 1. |- | bgcolor="#eeeeee" | '''[[Na-H exchanger]]&nbsp;antagonists''' | [[dopamine]]<ref name=boron875> {{cite book |author=Walter F., Boron |title=Medical Physiology: A Cellular And Molecular Approach |publisher=Elsevier/Saunders |location= |year=2004 |pages= |isbn=1-4160-2328-3 |oclc= |doi=}} Page 875 </ref> | bgcolor="#ddeeff" | promote Na<sup>+</sup> excretion | 2. [[proximal tubule]]<ref name=boron875/> |- | bgcolor="#eeeeee" | '''[[Carbonic anhydrase inhibitors|Carbonic&nbsp;anhydrase&nbsp;inhibitors]]''' | [[acetazolamide]]<ref name=boron875/>, [[dorzolamide]] | bgcolor="#ddeeff" | inhibit H<sup>+</sup> secretion, resultant promotion of Na<sup>+</sup> and K<sup>+</sup> excretion | 2: [[proximal tubule]] |- | bgcolor="#eeeeee" | '''[[Loop diuretic]]s''' | [[bumetanide]]<ref name=boron875/>, [[ethacrynic acid]]<ref name=boron875/>, [[furosemide]]<ref name=boron875/>, [[torsemide]] | bgcolor="#ddeeff" | inhibit the [[Na-K-2Cl symporter]] | 3. medullary [[thick ascending limb]] |- | bgcolor="#eeeeee" | '''[[Osmotic]] diuretics''' | [[glucose]] (especially in uncontrolled diabetes), [[mannitol]] | bgcolor="#ddeeff" | promote osmotic diuresis | 2. [[proximal tubule]], [[Descending limb of loop of Henle|descending limb]] |- | bgcolor="#eeeeee" | '''[[Potassium-sparing diuretic]]s''' | [[amiloride]], [[spironolactone]], [[triamterene]], [[potassium canrenoate]]. | bgcolor="#ddeeff" | inhibition of [[Na+/K+-ATPase|Na+/K+ exchanger]]: Spironolactone inhibits [[aldosterone]] action, Amiloride inhibits [[epithelial sodium channel]]s<ref name=boron875/> | 5. [[cortical collecting ducts]] |- | bgcolor="#eeeeee" | '''[[Thiazide]]s''' | [[bendroflumethiazide]], [[hydrochlorothiazide]] | bgcolor="#ddeeff" | inhibit reabsorption by [[Sodium-chloride symporter|Na<sup>+</sup>/Cl<sup>-</sup> symporter]] | 4. [[distal convoluted tubules]] |- | bgcolor="#eeeeee" | '''[[Xanthine]]s''' | [[caffeine]], [[theophylline]] | bgcolor="#ddeeff" | inhibit reabsorption of Na<sup>+</sup>, increase [[glomerular filtration rate]] | 1. tubules |- |} Chemically, diuretics are a diverse group of compounds that either stimulate or inhibit various [[hormone]]s that naturally occur in the body to regulate urine production by the kidneys. [[Herbs|Herbal medications]] are not inherently diuretics. They are more correctly called [[aquaretics]]. ==Adverse effects== The main adverse effects of diuretics are [[hypovolemia]], [[hypokalemia]], [[hyperkalemia]], [[hyponatremia]], [[metabolic alkalosis]], [[metabolic acidosis]] and [[hyperuricemia]] <ref name=boron875/>. Each are at risk of certain types of diuretics and present with different symptoms. {| class="wikitable sortable" |- ! [[Adverse effect]] ! Diuretics ! Symptoms |- | [[Hypovolemia]] | *[[loop diuretic]]s<ref name=boron875/> *[[thiazide]]s<ref name=boron875/> | *[[lassitude]]<ref name=boron875/> *[[thirst]]<ref name=boron875/> *[[muscle cramps]]<ref name=boron875/> *[[hypotension]]<ref name=boron875/> |- | [[hypokalemia]] | *[[acetazolamide]]s<ref name=boron875/> *[[loop diuretic]]s<ref name=boron875/> *[[thiazide]]s<ref name=boron875/> | *[[muscle weakness]]<ref name=boron875/> *[[paralysis]]<ref name=boron875/> *[[arrhythmia]]<ref name=boron875/> |- | [[Hyperkalemia]] | *[[amiloride]]s<ref name=boron875/> *[[triamterene]]s<ref name=boron875/> *[[spironolactone]]<ref name=boron875/> | *[[arrhythmia]]<ref name=boron875/> *[[muscle cramp]]s<ref name=boron875/> *[[paralysis]]<ref name=boron875/> |- | [[hyponatremia]] | *[[thiazide]]s<ref name=boron875/> *[[furosemide]]s<ref name=boron875/> | *[[CNS symptoms]]<ref name=boron875/> **[[coma]]<ref name=boron875/> |- | [[metabolic alkalosis]] | *[[loop diuretic]]s<ref name=boron875/> *[[thiazide]]s<ref name=boron875/> | *[[arrhythmia]]<ref name=boron875/> *[[CNS symptom]]s<ref name=boron875/> |- | [[metabolic acidosis]] | *[[acetazolamide]]s<ref name=boron875/> *[[amiloride]]s<ref name=boron875/> *[[triamterene]]<ref name=boron875/> | *[[Kussmaul respirations]]<ref name=boron875/> *[[muscle weakness]] *[[neurological symptoms]]<ref name=boron875/> **[[lethargy]] **[[coma]] **[[seizures.]] **[[stupor]] |- | [[hypercalcemia]] | *[[thiazide]]s<ref name=boron875/> | *[[gout]] *tissue [[calcification]]<ref name=boron875/> *[[Fatigue (medical)|fatigue]] *[[Depression (mood)|depression]] *[[confusion]] *[[anorexia]] *[[nausea]] *[[vomiting]] *[[constipation]] *[[pancreatitis]] *[[increased urination]] |- | [[hyperuricemia]] | *[[thiazide]]s<ref name=boron875/> *[[loop diuretic]]s<ref name=boron875/> | *[[gout]]<ref name=boron875/> |- |} ==References== {{reflist}} ==External links== * [http://cvpharmacology.com/diuretic/diuretics.htm Diagram at cvpharmacology.com] {{Antihypertensives and diuretics}} {{Major Drug Groups}} {{PAH rx}} [[Category:Diuretics|*]] [[bg:Диуретик]] [[bs:Diuretik]] [[ca:Diürètic]] [[cs:Diuretikum]] [[de:Diuretikum]] [[es:Diurético]] [[fr:Diurétique]] [[hr:Diuretici]] [[it:Diuretici]] [[he:משתן]] [[pam:Diuretic]] [[lt:Diuretikai]] [[nl:Diureticum]] [[ja:利尿薬]] [[no:Diuretikum]] [[nn:Urindrivande lækjemiddel]] [[pl:Leki moczopędne]] [[pt:Diurético]] [[ro:Diuretic]] [[ru:Диуретики]] [[simple:Diuretic]] [[sl:Diuretik]] [[sr:Диуретик]] [[fi:Diureetti]] [[sv:Vätskedrivande medel]] [[th:ยาขับปัสสาวะ]] [[uk:Діуретики]] [[zh:利尿劑]]