This illustration shows where some types of diuretics act, and what they do. A diuretic is any drug that elevates the rate of urination and thus provides a means of forced diuresis. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way. Contents 1 Types 1.1 High ceiling loop diuretics 1.2 Thiazides 1.3 Carbonic Anhydrase Inhibitors 1.4 Digitalis 1.5 Potassium-sparing diuretics 1.6 Calcium-sparing diuretics 1.7 Osmotic diuretics 1.8 Low ceiling diuretics 2 Uses 3 Mechanism of action 4 Adverse effects 5 See also 6 References 7 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 when compared to normal renal sodium reabsorption which 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 nephron 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 Thiazide-type diuretics such as hydrochlorothiazide act on the distal convoluted tubule and inhibit the sodium-chloride symporter leading to a retention of water in the urine, as water normally follows penetrating solutes. Frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure. On the other hand the long-term effect is due to an unknown vasodilator effect that decreases blood pressure by decreasing resistance. Carbonic Anhydrase Inhibitors

Carbonic anhydrase inhibitors inhibit the enzyme carbonic anhydrase which is found in the proximal convoluted tubule. This results in several effects including bicarbonate retention in the urine, potassium retention in urine and decreased sodium absorption. Drugs in this class include acetazolamide and methazolamide. Digitalis Digitalis increases output of urine by increasing cardiac output and increasing circulation through the kidneys. Digitalis has a diuretic effect on heart failure patients due to cardiac edema. 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. The term "potassium-sparing" refers to an effect rather than a mechanism or location; nonetheless, the term almost always refers to two specific classes that have their effect at similar locations: Aldosterone antagonists: 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. A similar agent is potassium canreonate. Epithelial sodium channel blockers: amiloride and triamterene. Calcium-sparing diuretics The term "calcium-sparing diuretic" is sometimes used to identify agents that result in a relatively low rate of excretion of calcium.2 The reduced concentration of calcium in the urine can lead to an increased rate of calcium in serum. The sparing effect on calcium can be beneficial in hypocalcemia, or unwanted in hypercalcemia.

The thiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics.3 The thiazides cause a net decrease in calcium lost in urine.4 The potassium-sparing diuretics cause a net increase in calcium lost in urine, but the increase is much smaller than the increase associated with other diuretic classes.4 By contrast, loop diuretics promote a significant increase calcium excretion.5 This can increase risk of reduced bone density.6 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 (hyperglycemia) exceeds the maximum reabsorption capacity of the kidney. When this happens, glucose remains in the filtrate, leading to the osmotic retention of water in the urine. Glucosuria causes a loss of hypotonic water and Na+ leading to a hypertonic state with signs of volume depletion such as: dry mucosa, hypotension, tachycardia, and decreased turgor of the skin. 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.7 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 dopamine8 promote Na+ excretion 2. proximal tubule8 Carbonic anhydrase inhibitors acetazolamide8, dorzolamide inhibit H+ secretion, resultant promotion of Na+ and K+ excretion 2: proximal tubule Loop diuretics bumetanide8, ethacrynic acid8, furosemide8, 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 channels8 5. cortical collecting ducts Thiazides bendroflumethiazide, hydrochlorothiazide inhibit reabsorption by Na+/Cl- symporter 4. distal convoluted tubules Xanthines caffeinecitation needed, theophylline, theobromine 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 8. Adverse effect Diuretics Symptoms Hypovolemia loop diuretics8 thiazides8 lassitude8 thirst8 muscle cramps8 hypotension8 hypokalemia acetazolamides8 loop diuretics8 thiazides8 muscle weakness8 paralysis8 arrhythmia8 Hyperkalemia amilorides8 triamterenes8 spironolactone8 arrhythmia8 muscle cramps8 paralysis8 hyponatremia thiazides8 furosemides8 CNS symptoms8 coma8 metabolic alkalosis loop diuretics8 thiazides8 arrhythmia8 CNS symptoms8 metabolic acidosis acetazolamides8 amilorides8 triamterene8 Kussmaul respirations8 muscle weakness neurological symptoms8 lethargy coma seizures stupor hypercalcemia thiazides8 gout tissue calcification8 fatigue depression confusion anorexia nausea vomiting constipation pancreatitis increased urination hyperuricemia thiazides8 loop diuretics8 gout8 See also antidiuretic References ^ Drug Monitor - Diuretics ^ Shankaran S, Liang KC, Ilagan N, Fleischmann L (April 1995). "Mineral excretion following furosemide compared with bumetanide therapy in premature infants". Pediatr. Nephrol. 9 (2): 159–62. doi:10.1007/BF00860731. PMID 7794709.  ^ Bakhireva LN, Barrett-Connor E, Kritz-Silverstein D, Morton DJ (June 2004). "Modifiable predictors of bone loss in older men: a prospective study". Am J Prev Med 26 (5): 436–42. doi:10.1016/j.amepre.2004.02.013. PMID 15165661. http://linkinghub.elsevier.com/retrieve/pii/S0749379704000406.  ^ a b Champe, Pamela C.; Richard Hubbard Howland; Mary Julia Mycek; Harvey, Richard P. (2006). Pharmacology. Philadelphia: Lippincott William & Wilkins. pp. 269. ISBN 0-7817-4118-1.  ^ Rejnmark L, Vestergaard P, Pedersen AR, Heickendorff L, Andreasen F, Mosekilde L (January 2003). "Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women". Eur. J. Clin. Invest. 33 (1): 41–50. doi:10.1046/j.1365-2362.2003.01103.x. PMID 12492451. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2972&date=2003&volume=33&issue=1&spage=41.  ^ Rejnmark L, Vestergaard P, Heickendorff L, Andreasen F, Mosekilde L (January 2006). "Loop diuretics increase bone turnover and decrease BMD in osteopenic postmenopausal women: results from a randomized controlled study with bumetanide". J. Bone Miner. Res. 21 (1): 163–70. doi:10.1359/JBMR.051003. PMID 16355285. http://www.jbmronline.com/doi/abs/10.1359/JBMR.051003?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov.  ^ Mutschler, Ernst (1995). Drug actions: basic principles and therapeutic aspects. Stuttgart, German: Medpharm Scientific Pub. pp. 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. pp. 875. ISBN 1-4160-2328-3.  External links Diagram at cvpharmacology.com v · d · eAntihypertensives: diuretics (C03) Sulfonamides (except EA) CA inhibitors (at PT) Acetazolamide Loop (Na-K-Cl at AL) Furosemide# • Bumetanide • Torasemide • Etacrynic acid Thiazides (Na-Cl at DCT, Calcium-sparing) Hydrochlorothiazide# • Bendroflumethiazide • Hydroflumethiazide • Chlorothiazide • Polythiazide • Trichlormethiazide • Cyclopenthiazide • Methyclothiazide • Cyclothiazide • Mebutizide Thiazide-likes (primarily DCT) Quinethazone • Clopamide • Chlortalidone • Mefruside • Clofenamide • Metolazone • Meticrane • Xipamide • Indapamide • Clorexolone • Fenquizone Potassium-sparing (at CD) ESC blockers Amiloride# • Triamterene • Benzamil Aldosterone antagonists Spironolactone# • Eplerenone • Potassium canrenoate • Canrenone Osmotic diuretics (PT, DL) Mannitol# • Urea VAs (DCT and CD)

vaptans: Conivaptan • Mozavaptan • Satavaptan • Tolvaptan tetracyclines: Demeclocycline Other mercurial diuretic (Mersalyl) • Theobromine • Cicletanine #WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III M: VAS anat(a:h, u, t, a, l,v:h, u, t, a, l)/phys/devp/cell/prot noco/syva/cong/tumr, sysi/epon proc, drug(C2s/n, C3, C4, C5, C7, C8, C9) v · d · ePharmacology: 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 (Antiplatelets, Anticoagulants, Thrombolytics/fibrinolytics) • Antihemorrhagics (Platelets, Coagulants, Antifibrinolytics) Cardiovascular system (C) cardiac therapy/antianginals (Cardiac glycosides, Antiarrhythmics, Cardiac stimulants) Antihypertensives • Diuretics • Vasodilators • Beta blockers • Calcium channel blockers • renin-angiotensin system (ACE inhibitors, Angiotensin II receptor antagonists, Renin inhibitors) Antihyperlipidemics (Statins, Fibrates, Bile acid sequestrants) Skin (D) Emollients • Cicatrizants • Antipruritics • Antipsoriatics • Medicated dressings Genitourinary system (G) Hormonal contraception • Fertility agents • SERMs • Sex hormones Endocrine system (H) Hypothalamic-pituitary hormones • Corticosteroids (Glucocorticoids, Mineralocorticoids) • Sex hormones • Thyroid hormones/Antithyroid agents Infections and infestations (J, P, QI) Antimicrobials: Antibacterials (Antimycobacterials) • Antifungals • Antivirals • Antiparasitics (Antiprotozoals, Anthelmintics, Ectoparasiticides) • IVIG • Vaccines Malignant disease (L01-L02) Anticancer agents (Antimetabolites, Alkylating, Spindle poisons, Antineoplastic, Topoisomerase inhibitors) Immune disease (L03-L04) Immunomodulators (Immunostimulants, Immunosuppressants) Muscles, bones, and joints (M) Anabolic steroids • Anti-inflammatories (NSAIDs) • Antirheumatics • Corticosteroids • Muscle relaxants • Bisphosphonates Brain and nervous system (N) Analgesics • Anesthetics (General, Local) • Anorectics • Anti-ADHD Agents • Antiaddictives • Anticonvulsants • Antidementia Agents • Antidepressants • Antimigraine Agents • Antiparkinson's Agents • Antipsychotics • Anxiolytics • Depressants • Entactogens • Entheogens • Euphoriants • Hallucinogens (Psychedelics, Dissociatives, Deliriants) • Hypnotics/Sedatives • Mood Stabilizers • Neuroprotectives • Nootropics • Neurotoxins • Orexigenics • Serenics • Stimulants • Wakefulness-Promoting Agents Respiratory system (R) Decongestants • Bronchodilators • Cough medicines • H1 antagonists Sensory organs (S) Ophthalmologicals • Otologicals Other ATC (V) Antidotes • Contrast media • Radiopharmaceuticals • Dressings v · d · eMedications used in the management of pulmonary arterial hypertension (B01, C02) Prostacyclin analogues Beraprost, Epoprostenol, Iloprost, Treprostinil Endothelin receptor antagonists Ambrisentan, Bosentan, Sitaxentan PDE5 inhibitors Sildenafil, Tadalafil Adjunctive therapy Calcium channel blockers, Diuretics, Digoxin, Oxygen therapy, Warfarin