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11-SEPTEMBER-2008 12:20:15 - Diuretic This illustration shows where some types of diuretics act, and what they do. This illustration shows where some types of diuretics act, and what they do. A diuretic is any drug that elevates the rate of 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. Contents 1 Types 1.1 High ceiling loop diuretics 1.2 Thiazides 1.3 Potassium-sparing diuretics 1.4 Osmotic diuretics 1.5 Low ceiling diuretics 2 Uses 3 Mechanism of action 4 Adverse effects 5 References 6 External links Types High ceiling loop diuretics High ceiling diuretics are diuretics that may cause a substantial diuresis - up to 20%1 of the filtered load of 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. 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 drugs, especially stimulants may also increase blood glucose and thus increase urination. Low ceiling diuretics The term low ceiling diuretic is used to indicate that a diuretic has a rapidly flattening dose effect curve in contrast to high ceiling, where the relationship is close to linear. It refers to a pharmacological profile, not a chemical structure. However, there are certain classes of diuretic which usually fall into this category, such as the thiazides.2 Uses In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension and certain kidney diseases. 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 overdose or poisoning. Diuretics are often abused by sufferers of eating disorders, especially bulimics, in attempts at weight loss. The antihypertensive actions of some diuretics thiazides and loop diuretics 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: Examples Mechanism Location numbered in distance along nephron - Ethanol, Water inhibits vasopressin secretion 1. Acidifying salts CaCl2, NH4Cl 1. Arginine vasopressin receptor 2 antagonists amphotericin B, lithium citrate inhibit vasopressin's action 5. collecting duct Aquaretics Goldenrod, Juniper Increases blood flow in kidneys 1. Na-H exchanger antagonists dopamine3 promote Na+ excretion 2. proximal tubule3 Carbonic anhydrase inhibitors acetazolamide3, dorzolamide inhibit H+ secretion, resultant promotion of Na+ and K+ excretion 2: proximal tubule Loop diuretics bumetanide3, ethacrynic acid3, furosemide3, torsemide inhibit the Na-K-2Cl symporter 3. medullary thick ascending limb Osmotic diuretics glucose especially in uncontrolled diabetes, mannitol promote osmotic diuresis 2. proximal tubule, descending limb Potassium-sparing diuretics amiloride, spironolactone, triamterene, potassium canrenoate. inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels3 5. cortical collecting ducts Thiazides bendroflumethiazide, hydrochlorothiazide inhibit reabsorption by Na+/Cl- symporter 4. distal convoluted tubules Xanthines caffeine, theophylline inhibit reabsorption of Na+, increase glomerular filtration rate 1. tubules Chemically, diuretics are a diverse group of compounds that either stimulate or inhibit various hormones that naturally occur in the body to regulate urine production by the kidneys. 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 3. Each are at risk of certain types of diuretics and present with different symptoms. Adverse effect Diuretics Symptoms Hypovolemia loop diuretics3 thiazides3 lassitude3 thirst3 muscle cramps3 hypotension3 hypokalemia acetazolamides3 loop diuretics3 thiazides3 muscle weakness3 paralysis3 arrhythmia3 Hyperkalemia amilorides3 triamterenes3 spironolactone3 arrhythmia3 muscle cramps3 paralysis3 hyponatremia thiazides3 furosemides3 CNS symptoms3 coma3 metabolic alkalosis loop diuretics3 thiazides3 arrhythmia3 CNS symptoms3 metabolic acidosis acetazolamides3 amilorides3 triamterene3 Kussmaul respirations3 muscle weakness neurological symptoms3 lethargy coma seizures. stupor hypercalcemia thiazides3 gout tissue calcification3 fatigue depression confusion anorexia nausea vomiting constipation pancreatitis increased urination hyperuricemia thiazides3 loop diuretics3 gout3 References ^ Drug Monitor - Diuretics ^ Mutschler, Ernst 1995. Drug actions: basic principles and theraputic aspects. Stuttgart, German: Medpharm Scientific Pub, 460. ISBN 0-8493-7774-9. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar Boron, Walter F. 2004. Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders, 875. ISBN 1-4160-2328-3. External links Diagram at cvpharmacology.com 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 CA inhibitor at PT Acetazolamide Osmotic Mannitol Urea Other Mersalyl Theobromine Cicletanine High ceiling/ Loop diuretic at AL Bumetanide Furosemide Torasemide Etacrynic acid Potassium-sparing at CD ESC blockers Amiloride, Triamterene, Benzamil aldosterone antagonists Spironolactone, Eplerenone, Potassium canrenoate, Canrenone v d e Major drug groups Gastrointestinal tract/metabolism A stomach acid Antacids, H2 antagonists, Proton pump inhibitors Antiemetics Laxatives Antidiarrhoeals/Antipropulsives Anti-obesity drugs Anti-diabetics Vitamins Dietary minerals Blood and blood forming organs B Antithrombotics Anticoagulants, Antiplatelets, Thrombolytics Antihemorrhagics Cardiovascular system C cardiac therapy/antianginals Cardiac glycosides, Antiarrhythmics, Cardiac stimulant Antihypertensives Diuretics Vasodilators Beta blockers renin-angiotensin system ACE inhibitors, Angiotensin II receptor antagonists, Renin inhibitors Antihyperlipidemics Skin D Emollients Cicatrizant Antipruritics Reproductive system G Hormonal contraception Fertility agents SERMs Sex hormones Endocrine system H Corticosteroids Sex hormones Thyroid hormones Antithyroid agent Infections and infestations J, P Antibiotics Antivirals Vaccines Antifungals Antiparasitic Antiprotozoals, Anthelmintics Malignant and immune disease L Anticancer agents Immunostimulators Immunosuppressants Muscles, bones, and joints M Anabolic steroids Anti-inflammatories NSAID Antirheumatics Corticosteroids Muscle relaxants Brain and nervous system N Anesthetics General, Local Analgesics Anticonvulsants Mood stabilizers Psycholeptic Anxiolytics, Antipsychotics, Hypnotics/Sedatives Psychoanaleptic Antidepressants, Stimulants/Psychostimulants Respiratory system R Bronchodilators Decongestants H1 antagonists Other ATC V Antidotes Contrast media Radiopharmaceuticals Dressing v d e Medications used in the management of pulmonary arterial hypertension B01, C02 Prostacyclin analogues Beraprost, Epoprostenol, Iloprost, Treprostinil Endothelin receptor antagonists Ambrisentan, Bosentan, Sitaxsentan PDE5 inhibitors Sildenafil, Tadalafil Adjunctive therapy Calcium channel blockers, Diuretics, Digoxin, Oxygen therapy, Warfarin Retrieved from http://en..org/wiki/Diuretic Categories: Diuretics 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 Türkçe БългарÑ?ки Bosanski Català Česky Deutsch Español Français Hrvatski Italiano עברית Kapampangan Lietuvių Nederlands 日本語 ‪Norsk bokmÃ¥l‬ ‪Norsk nynorsk‬ Polski Português Română РуÑ?Ñ?кий Simple English SlovenÅ¡Ä?ina СрпÑ?ки / Srpski Suomi Svenska ไทย УкраїнÑ?ька ä¸æ–‡ This page was last modified on 4 September 2008, at 02:05
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