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Diuretic

(Redirected from Diuretics)

A diuretic (/ˌdaɪjʊˈrɛtɪk/) is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics increase the excretion of water from the body, through the kidneys. There exist several classes of diuretic, and each works in a distinct way. Alternatively, an antidiuretic, such as vasopressin (antidiuretic hormone), is an agent or drug which reduces the excretion of water in urine.

Diuretics
Drug class
Furosemide 125 mg vials for intravenous application
Class identifiers
UseForced diuresis, hypertension
ATC codeC03
External links
MeSHD004232
Legal status
In Wikidata

Medical uses

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In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension, influenza, water poisoning, 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 sometimes abused by people with an eating disorder, especially people with bulimia nervosa, with the goal of losing weight.[citation needed]

The antihypertensive actions of some diuretics (thiazides and loop diuretics in particular) are independent of their diuretic effect.[1][2] 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.[citation needed]

Types

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High-ceiling/loop diuretics

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High-ceiling diuretics may cause a substantial diuresis – up to 20%[3] of the filtered load of NaCl (salt) and water. This is large in comparison to normal renal sodium reabsorption which leaves only about 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 an excretion of water in the urine, whereas water normally follows sodium back into the extracellular fluid. Other examples of high-ceiling loop diuretics include ethacrynic acid and torasemide.[citation needed]

Thiazides

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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.[4]

Carbonic anhydrase inhibitors

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Carbonic anhydrase inhibitors inhibit the enzyme carbonic anhydrase which is found in the proximal convoluted tubule. This results in several effects including bicarbonate accumulation in the urine and decreased sodium absorption. Drugs in this class include acetazolamide and methazolamide.[citation needed]

Potassium-sparing diuretics

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These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is retained and not lost as much as with other diuretics.[citation needed] 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:

Calcium-sparing diuretics

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The term "calcium-sparing diuretic" is sometimes used to identify agents that result in a relatively low rate of excretion of calcium.[5]

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.[citation needed]

The thiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics.[6]

  • The thiazides cause a net decrease in calcium lost in urine.[7]
  • 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.[7]

By contrast, loop diuretics promote a significant increase in calcium excretion.[8] This can increase risk of reduced bone density.[9]

Osmotic diuretics

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Osmotic diuretics (e. g., mannitol) are substances that increase osmolarity, but have limited tubular epithelial cell permeability. They work primarily by expanding extracellular fluid and plasma volume, therefore increasing blood flow to the kidney, particularly the peritubular capillaries. This reduces medullary osmolality and thus impairs the concentration of urine in the loop of Henle (which usually uses the high osmotic and solute gradient to transport solutes and water). Further, the limited tubular epithelial cell permeability increases osmolality and thus water retention in the filtrate.[10]

It was previously believed that the primary mechanism of osmotic diuretics such as mannitol is that they are filtered in the glomerulus, but cannot be reabsorbed. Thus their presence leads to an increase in the osmolarity of the filtrate and to maintain osmotic balance, water is retained in the urine.[citation needed]

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.[citation needed].

Low-ceiling diuretics

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The term "low-ceiling diuretic" is used to indicate a diuretic has a rapidly flattening dose effect curve (in contrast to "high-ceiling", where the relationship is close to linear). Certain classes of diuretic are in this category, such as the thiazides.[11]

Mechanism of action

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Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure. Loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 and exert their diuretic action by binding to the Na(+)-K(+)-2Cl(-) co-transporter type 2 in the thick ascending limb and the Na(+)-Cl(-) co-transporter in the distal convoluted tubule, respectively.[12]

Classification of common diuretics and their mechanisms of action.
Class Examples Mechanism Location (numbered in distance along nephron)
Ethanol drinking alcohol Inhibits vasopressin secretion
Water Inhibits vasopressin secretion
Acidifying salts calcium chloride, ammonium chloride 1.
Arginine vasopressin
receptor 2 antagonists 		amphotericin B, lithium[13][14] Inhibits vasopressin's action 5. collecting duct
Selective vasopressin V2 antagonist (sometimes called aquaretics) tolvaptan,[15] conivaptan Competitive vasopressin antagonism leads to decreased number of aquaporin channels in the apical membrane of the renal collecting ducts in kidneys, causing decreased water reabsorption. This causes an increase in renal free water excretion (aquaresis), an increase in serum sodium concentration, a decrease in urine osmolality, and an increase in urine output.[16] 5. collecting duct
Na-H exchanger antagonists dopamine[17] Promotes Na+ excretion 2. proximal tubule[17]
Carbonic anhydrase inhibitors acetazolamide,[17] dorzolamide Inhibits H+ secretion, resultant promotion of Na+ and K+ excretion 2. proximal tubule
Loop diuretics bumetanide,[17] ethacrynic acid,[17] furosemide,[17] torsemide Inhibits the Na-K-2Cl symporter 3. medullary thick ascending limb
Osmotic diuretics glucose (especially in uncontrolled diabetes), mannitol Promotes osmotic diuresis 2. proximal tubule, descending limb
Potassium-sparing diuretics amiloride, spironolactone, eplerenone, triamterene, potassium canrenoate. Inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels[17] 5. cortical collecting ducts
Thiazides bendroflumethiazide, hydrochlorothiazide Inhibits reabsorption by Na+/Cl− symporter 4. distal convoluted tubules
Xanthines caffeine, theophylline, theobromine Inhibits reabsorption of Na+, increase glomerular filtration rate 1. tubules

Caffeine when initially consumed in large quantities is both a diuretic and a natriuretic,[18] but this effect disappears with chronic consumption.[19][20][21]

Adverse effects

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The main adverse effects of diuretics are hypovolemia, hypokalemia, hyperkalemia, hyponatremia, metabolic alkalosis, metabolic acidosis, and hyperuricemia.[17]

Adverse effect Diuretics Symptoms
hypovolemia
hypokalemia
hyperkalemia
hyponatremia
metabolic alkalosis
metabolic acidosis
hypercalcemia
hyperuricemia

Abuse in sports

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A common application of diuretics is for the purposes of invalidating drug tests.[22] Diuretics increase the urine volume and dilute doping agents and their metabolites. Another use is to rapidly lose weight to meet a weight category in sports like boxing and wrestling.[23][24]

See also

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References

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  1. ^ Shah, Shaukat; Khatri, Ibrahim; Freis, Edward D. (1978). "Mechanism of antihypertensive effect of thiazide diuretics". American Heart Journal. 95 (5): 611–618. doi:10.1016/0002-8703(78)90303-4. PMID 637001.
  2. ^ Ballew JR, Fink GD (September 2001). "Characterization of the antihypertensive effect of a thiazide diuretic in angiotensin II-induced hypertension". Journal of Hypertension. 19 (9): 1601–6. doi:10.1097/00004872-200109000-00012. PMID 11564980. S2CID 8531997.
  3. ^ "TheDrugMonitor.com is available at DomainMarket.com". TheDrugMonitor.com is available at DomainMarket.com. Archived from the original on January 17, 2008.
  4. ^ Julio D. Duarte; Rhonda M. Cooper-DeHoff (April 1, 2011). "Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics". Expert Review of Cardiovascular Therapy. 8 (6): 793–802. doi:10.1586/erc.10.27. PMC 2904515. PMID 20528637.
  5. ^ 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. S2CID 21202583.
  6. ^ 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.
  7. ^ a b Champe, Pamela C.; Richard Hubbard Howland; Mary Julia Mycek; Harvey, Richard P. (2006). Pharmacology. Philadelphia: Lippincott William & Wilkins. p. 269. ISBN 978-0-7817-4118-7.
  8. ^ 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. S2CID 36030615.
  9. ^ 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. S2CID 41216704.
  10. ^ Du, Xiaoping. Diuretics Archived April 7, 2006, at the Wayback Machine. Department of Pharmacology, University of Illinois at Chicago.
  11. ^ Mutschler, Ernst (1995). Drug actions: basic principles and therapeutic aspects. Stuttgart, German: Medpharm Scientific Pub. p. 460. ISBN 978-0-8493-7774-7.
  12. ^ Ali SS, Sharma PK, Garg VK, Singh AK, Mondal SC (Apr 2012). "The target-specific transporter and current status of diuretics as antihypertensive". Fundam Clin Pharmacol. 26 (2): 175–9. doi:10.1111/j.1472-8206.2011.01012.x. PMID 22145583. S2CID 43171023.
  13. ^ Ajay K. Singh; Gordon H. Williams (12 January 2009). Textbook of Nephro-Endocrinology. Academic Press. pp. 250–251. ISBN 978-0-08-092046-7.
  14. ^ L. Kovács; B. Lichardus (6 December 2012). Vasopressin: Disturbed Secretion and Its Effects. Springer Science & Business Media. pp. 179–180. ISBN 978-94-009-0449-1.
  15. ^ Schrier, Robert W.; Gross, Peter; Gheorghiade, Mihai; Berl, Tomas; Verbalis, Joseph G.; Czerwiec, Frank S.; Orlandi, Cesare (2006-11-16). "Tolvaptan, a Selective Oral Vasopressin V2-Receptor Antagonist, for Hyponatremia". New England Journal of Medicine. 355 (20): 2099–2112. doi:10.1056/NEJMoa065181. hdl:2437/157922. ISSN 0028-4793. PMID 17105757.
  16. ^ Reilly, Timothy; Chavez, Benjamin (2009-10-01). "Tolvaptan (samsca) for hyponatremia: is it worth its salt?". Pharmacy and Therapeutics. 34 (10): 543–547. PMC 2799145.
  17. ^ 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. p. 875. ISBN 978-1-4160-2328-9.
  18. ^ Maughan RJ, Griffin J (December 2003). "Caffeine ingestion and fluid balance: a review" (PDF). Journal of Human Nutrition and Dietetics. 16 (6): 411–20. doi:10.1046/j.1365-277X.2003.00477.x. PMID 19774754. S2CID 41617469. Archived from the original (PDF) on 8 March 2019.
  19. ^ O'Connor A (4 March 2008). "Really? The claim: caffeine causes dehydration". New York Times. Retrieved 3 August 2009.
  20. ^ Armstrong LE, Casa DJ, Maresh CM, Ganio MS (July 2007). "Caffeine, fluid-electrolyte balance, temperature regulation, and exercise-heat tolerance". Exercise and Sport Sciences Reviews. 35 (3): 135–40. doi:10.1097/jes.0b013e3180a02cc1. PMID 17620932. S2CID 46352603.
  21. ^ Maughan RJ, Watson P, Cordery PA, Walsh NP, Oliver SJ, Dolci A, et al. (March 2016). "A randomized trial to assess the potential of different beverages to affect hydration status: development of a beverage hydration index". The American Journal of Clinical Nutrition. 103 (3): 717–23. doi:10.3945/ajcn.115.114769. hdl:1893/22892. PMID 26702122. S2CID 378245.
  22. ^ Bahrke, Michael (2002). Performance-Enhancing Substances in Sport and Exercise.
  23. ^ Agence France Presse (2012-07-17). "UCI announces adverse analytical finding for Frank Schleck". VeloNews. Retrieved 2012-07-18.
  24. ^ Cadwallader AB, de la Torre X, Tieri A, Botrè F (September 2010). "The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysis". British Journal of Pharmacology. 161 (1): 1–16. doi:10.1111/j.1476-5381.2010.00789.x. PMC 2962812. PMID 20718736.
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