Diuretic
This illustration shows where some types of diuretics act, and what they do.

A diuretic provides a means of forced diuresis which elevates the rate of urination. 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

Types

High ceiling loop diuretic

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.

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:

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[8] .

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 dopamine[9] promote Na+ excretion 2. proximal tubule[9]
Carbonic anhydrase inhibitors acetazolamide,[9] dorzolamide inhibit H+ secretion, resultant promotion of Na+ and K+ excretion 2: proximal tubule
Loop diuretics bumetanide,[9] ethacrynic acid,[9] furosemide,[9] 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 channels[9] 5. cortical collecting ducts
Thiazides bendroflumethiazide, hydrochlorothiazide inhibit reabsorption by Na+/Cl- symporter 4. distal convoluted tubules
Xanthines caffeine, 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.[9]

Adverse effect Diuretics Symptoms
Hypovolemia
hypokalemia
Hyperkalemia
hyponatremia
metabolic alkalosis
  • arrhythmia[9]
  • CNS symptoms[9]
metabolic acidosis
hypercalcemia
hyperuricemia

See also

References

  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. http://linkinghub.elsevier.com/retrieve/pii/S0749379704000406. 
  4. ^ 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. 
  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. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0014-2972&date=2003&volume=33&issue=1&spage=41. 
  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. 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. 
  7. ^ Mutschler, Ernst (1995). Drug actions: basic principles and therapeutic aspects. Stuttgart, German: Medpharm Scientific Pub. pp. 460. ISBN 0-8493-7774-9. 
  8. ^ Smith, Mary. "Ms.". Registered Nurse / Gym Instructor. diureticsoverthecounter. http://diureticsoverthecounter.com/. Retrieved Oct 17, 2011. 
  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. 

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Look at other dictionaries:

  • diuretic — DIURÉTIC, Ă, diuretici, ce, adj., s.n. (Medicament, ceai etc.) care produce sau măreşte diureza. [pr.: di u ] – Din fr. diurétique, lat. diureticus. Trimis de LauraGellner, 18.06.2004. Sursa: DEX 98  diurétic adj. m. (sil. di u ) …   Dicționar Român

  • Diuretic — Di u*ret ic, a. [L. diureticus, Gr. ?, fr. ? to make water; ? through + ? to make water, fr. ? urine: cf. F. diur[ e]tique.] (Med.) Tending to increase the secretion and discharge of urine. n. A medicine with diuretic properties. [1913 Webster]… …   The Collaborative International Dictionary of English

  • diuretic — Medicine ► ADJECTIVE ▪ causing increased passing of urine. ► NOUN ▪ a diuretic drug. ORIGIN Greek diour tikos, from diourein urinate …   English terms dictionary

  • diuretic — [dī΄yo͞oret′ik] adj. [ME diuretik < LL diureticus < Gr diourētikos < diourein: see DIURESIS] increasing the excretion of urine n. a diuretic drug or other substance diuretically adv …   English World dictionary

  • diuretic — c.1400 (adj. and noun), from O.Fr. diuretique, from L.L. diureticus, from Gk. diouretikos prompting urine, from diourein urinate, from dia through (see DIA (Cf. dia )) + ourein urinate, from ouron (see URINE (Cf …   Etymology dictionary

  • diuretic — [[t]da͟ɪ͟əre̱tɪk[/t]] diuretics N COUNT A diuretic is a substance which makes your body increase its production of waste fluids, with the result that you need to urinate more often than usual. [MEDICAL or TECHNICAL] Like caffeine, alcohol acts as …   English dictionary

  • diuretic — UK [ˌdaɪjʊˈretɪk] / US [ˌdaɪjəˈretɪk] noun [countable] Word forms diuretic : singular diuretic plural diuretics medical a substance that makes your body produce more urine Derived word: diuretic UK / US adjective Caffeine is known to have a… …   English dictionary

  • diuretic — adjective Etymology: Middle English duretik, diuretic, from Late Latin diureticus, from Greek diourētikos, from diourein to urinate, from dia + ourein to urinate more at urine Date: 14th century tending to increase the excretion of urine <… …   New Collegiate Dictionary

  • diuretic — 1. Promoting the excretion of urine. 2. An agent that increases the amount of urine excreted. cardiac d. a d. that acts by increasing function of the heart, and thereby improves renal perfusion. direct d. a d. whose primary …   Medical dictionary

  • diuretic — diuretically, adv. diureticalness, n. /duy euh ret ik/, adj. 1. increasing the volume of the urine excreted, as by a medicinal substance. n. 2. a diuretic medicine or agent. [1375 1425; ME d(i)uretik < LL diureticus < Gk diouretikós, equiv. to di …   Universalium

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