Diuretic

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Diuretic
Drug class
UseForced diuresis, hypertension
ATC codeC03
 
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Diuretic
Drug class
UseForced diuresis, hypertension
ATC codeC03

A diuretic is any substance that promotes the production of urine. This includes 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. Alternatively, an antidiuretic such as vasopressin is an agent or drug which reduces the excretion of water in urine.

Medical uses[edit]

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.

Types[edit]

High ceiling/loop diuretic[edit]

High ceiling diuretics may cause a substantial diuresis – up to 20%[1] of the filtered load of NaCl (salt) and water. This is huge when compared 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 torsemide.

Thiazides[edit]

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[edit]

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.

Potassium-sparing diuretics[edit]

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. 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[edit]

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]

By contrast, loop diuretics promote a significant increase calcium excretion.[5] This can increase risk of reduced bone density.[6]

Osmotic diuretics[edit]

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[edit]

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). It refers to a pharmacological profile, not a chemical structure. However, certain classes of diuretic usually fall into this category, such as the thiazides.[7]

Mechanism of action[edit]

Classification of common diuretics and their mechanisms of action:

ExamplesMechanismLocation (numbered in distance along nephron)
ethanol, waterInhibits vasopressin secretion1.
Acidifying saltsCaCl2, NH4Cl1.
Arginine vasopressin
receptor 2
 antagonists
amphotericin B, lithium citrateInhibits vasopressin's action5. collecting duct
AquareticsGoldenrod[citation needed], Juniper[citation needed]Increases blood flow in kidneys[citation needed]1.[citation needed]
Na-H exchanger antagonistsdopamine[8]Promotes Na+ excretion2. proximal tubule[8]
Carbonic anhydrase inhibitorsacetazolamide,[8] dorzolamideInhibits H+ secretion, resultant promotion of Na+ and K+ excretion2: proximal tubule
Loop diureticsbumetanide,[8] ethacrynic acid,[8] furosemide,[8] torsemideInhibits the Na-K-2Cl symporter3. medullary thick ascending limb
Osmotic diureticsglucose (especially in uncontrolled diabetes), mannitolPromotes osmotic diuresis2. proximal tubule, descending limb
Potassium-sparing diureticsamiloride, spironolactone, eplerenone, triamterene, potassium canrenoate.Inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels[8]5. cortical collecting ducts
Thiazidesbendroflumethiazide, hydrochlorothiazideInhibits reabsorption by Na+/Cl- symporter4. distal convoluted tubules
Xanthinescaffeine, theophylline, theobromineInhibits reabsorption of Na+, increase glomerular filtration rate1. 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.

As a diuretic is any substance that promotes the production of urine, aquaretics that cause the excretion of free water are a sub-class. This includes all the hypotonic aqueous preparations, including pure water, black and green teas, and teas prepared from Herbal medications. Any given herbal medication will include a vast range of plant-derived compounds, some of which will be active drugs that may also have independent diuretic action.

Adverse effects[edit]

The main adverse effects of diuretics are hypovolemia, hypokalemia, hyperkalemia, hyponatremia, metabolic alkalosis, metabolic acidosis and hyperuricemia.[8]

Adverse effectDiureticsSymptoms
Hypovolemia
hypokalemia
Hyperkalemia
hyponatremia
metabolic alkalosis
metabolic acidosis
hypercalcemia
hyperuricemia

Banned use in sports[edit]

The most effective use would be before a doping test. Diuretics increase the urine volume and dilute doping agents and their metabolites. The other use would be to rapidly lose weight to meet a weight category in sports like boxing, wrestling and others.[9][10]

See also[edit]

References[edit]

  1. ^ Drug Monitor – Diuretics
  2. ^ 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. 
  3. ^ 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. 
  4. ^ a b Champe, Pamela C.; Richard Hubbard Howland; Mary Julia Mycek; Harvey, Richard P. (2006). Pharmacology. Philadelphia: Lippincott William & Wilkins. p. 269. ISBN 0-7817-4118-1. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ Mutschler, Ernst (1995). Drug actions: basic principles and therapeutic aspects. Stuttgart, German: Medpharm Scientific Pub. p. 460. ISBN 0-8493-7774-9. 
  8. ^ 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 1-4160-2328-3. 
  9. ^ Agence France Presse (2012-07-17). "UCI announces adverse analytical finding for Frank Schleck". VeloNews. Retrieved 2012-07-18. 
  10. ^ The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysis, British Journal of Pharmacology, 2010-09.

External links[edit]