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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

Types

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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 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

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.

Digitalis

Digitalis has a diuretic effect on heart failure patients. [add more info]

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.

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[8] promote Na+ excretion 2. proximal tubule[8]
Carbonic anhydrase inhibitors acetazolamide[8], dorzolamide inhibit H+ secretion, resultant promotion of Na+ and K+ excretion 2: proximal tubule
Loop diuretics bumetanide[8], ethacrynic acid[8], furosemide[8], 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[8] 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 [8]. Each are at risk of certain types of diuretics and present with different symptoms.

Adverse effect Diuretics Symptoms
Hypovolemia
hypokalemia
Hyperkalemia
hyponatremia
metabolic alkalosis
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. 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. 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. ^ 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


1911 encyclopedia

Up to date as of January 14, 2010

From LoveToKnow 1911

DIURETICS (from Gr. & fl, through, and oupeav, pass urine), the name given to remedies which, under certain conditions, stimulate an increased flow of urine. Their mode of action is various. Some are absorbed into the blood, carried to the secretory organs (the kidneys), and stimulate them directly, causing an increased flow of blood; others act as stimulants through the nervous system. A second class act in congested conditions of the kidneys by diminishing the congestion. Another class, such as the saline diuretics, are effectual by virtue of their osmotic action. A fourth class are diuretic by increasing the blood pressure within the vessels in general, and the Malpighian tufts in particular, - some, as digitalis, by increasing the strength of the heart's contractions, and others, as water, by increasing the amount of fluid circulating in the vessels. Some remedies, as mercury, although not diuretic themselves, when prescribed along with those which have this action, increase their effect. The same remedy may act in more than one way, e.g. alcohol, besides stimulating the secretory organs directly, is a stimulant to the circulation, and thus increases the pressure within the vessels. Diuretics are prescribed when the quantity of urine is much diminished, or when, although the quantity may be normal, it is wished to relieve some other organ or set of organs of part of their ordinary work, or to aid in carrying off some morbid product circulating in the blood, or to hasten the removal of inflammatory serous exudations, or of dropsical collections of fluid. Caffeine, which is far the best true diuretic, acts in nearly every way mentioned above. Together with digitalis it is the most efficient remedy for cardiac dropsy. A famous diuretic pill, known as Guy's pill, consists of a grain each of mercurial pill, digitalis leaves and squill, made up with extract of henbane. Digitalis, producing its diuretic effect by its combined action on heart, vessels and kidneys, is much used in the oedema of mitral disease, but must be avoided in chronic Bright's disease, as it increases the tension of the pulse, already often dangerously high. Turpentine and cantharides are not now recommended as diuretics, as they are too irritating to the kidneys.


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