Diuretic

A diuretic (plural: diuretics ; from ancient Greek δι-ουρητικός di-uretikós "transporting the urine", from di [o] ureîn "urinate"; to οὖρον uron "urine, urine") is a medicine that causes an increased leaching of urine ( Diuresis ) from the human or animal body caused by increased urine production in the kidneys .

All modern diuretics inhibit tubular reabsorption . "According to Robert Pitts (1958), diuretics in the narrower sense partially inhibit the tubular sodium reabsorption" and thus also the tubular reabsorption of water.

This active principle also applies to drinking water during water diuresis , for example in the outdated water experiment for diagnostic reasons ("The simplest peripheral diuretic is the one-off sudden supply of large amounts of water").

For example, if the tubular reabsorption rate is reduced from 99% to 98%, then the urine production doubles from 1 to 2 percent of the primary urine. Likewise, the urine flow would double with a constant rate of re-absorption if the cardiac output and thus the glomerular filtration rate doubled; Because of their positive inotropy with diuretic effect, cardiac glycosides were previously prescribed for the treatment of heart failure.

Diuretics are used in the treatment of inadequate kidney function , peripheral edema and pulmonary edema, and for the treatment of high blood pressure and heart failure.

Most diuretics are saluretics ; They act by inhibiting the return resorption of sodium in the tubule ; the resulting loss of salt ( saluresis ) is therapeutically desirable as an intervention in the volume balance . For the treatment of osmotic disturbances exist alongside with the aquaretics ( vasopressin antagonists ) of diuretics, alone excretion of water (Aquarese) promoting. Colloquially Diuretics are also in tablet form diuretics or short water tablets called. Herbal medicinal products have only a subordinate therapeutic importance in addition to the chemically synthesized medicinal substances.

history

In medicine , diuretics and uses have been known for a very long time. A distinction must be made between procedures for increasing the glomerular function and procedures for reducing the tubular function. In 1785 William Withering published his "Report on the thimble and its medicinal uses with practical remarks on dropsy and other diseases".

An increase in cardiac output leads to an increase in renal perfusion and glomerular filtration. Even with unchanged tubular reabsorption, the urine flow increases. This is how the cardiac glycosides ( digitalis active ingredients ) work; they can increase cardiac output and thus the glomerular filtration rate by about a third. Better renal blood flow is achieved through the effects of heat on the Head's zones of the kidneys. Herbal tissue diuretics are supposed to cause water to be removed from the tissues. These methods are designed to improve blood circulation and increase stroke volume and blood pressure . The principle of action of tubular diuretics must be distinguished from this. In today's pharmacology , only these are called diuretics.

Purines were known as the first effective tubular diuretics . These include caffeine , theophylline, and theobromine . The latter was extracted from cocoa shells for the first time by Albert Knoll . From this, his company developed the theobromine preparation diuretin in 1889 . Subsequently, Byk Gulden synthesized theophylline-containing theocine in 1902 , which was mixed with ethylenediamine in 1908 ( euphylline ).

Almost at the same time, the mercury diuretics were discovered: the first industrially significant preparation was Novasurol ( Merbaphen ) introduced by Bayer AG in 1917 . From 1920 to 1961, numerous mercury preparations were examined for their diuretic effect. Some of these were introduced into therapy, sometimes in combination with the purines.

The carbonic anhydrase inhibitor acetazolamide is the first sulfonamide diuretic . This was sold from 1950 by the Lederle company. The detection of the diuretic acetazolamide in a speed skater from Japan was the first doping case at the 2018 Winter Olympics . In 1957 the chemists Frederick Novello and John Baer and the pharmacologist Karl Heinz Beyer discovered the new class of thiazide diuretics . The first came onto the market in 1959 as a chlorothiazide . In the same year, Ciba AG published the more potent hydrochlorothiazide (abbreviated as HCT, Esidrix ). While researching other thiazide diuretics, Roman Muschaweck and the chemist Paul Hajdu discovered the loop diuretic furosemide ( Lasix ), which is still the gold standard in diuretic therapy today (together with the more potent follow-on compound torasemide ).

The aldosterone antagonist spironolactone and the cyclic amidine derivatives triamterene and amiloride were subsequently developed between 1959 and 1966 as potassium-sparing diuretics .

Sequential nephron blockade has been a special diuretic therapy principle since 1985 .

Classification of diuretics

Depending on the site of attack and the mechanism of action, the diuretics that act on the tubule can be divided into different groups:

• Loop diuretics reversibly inhibit the Na ⁺ / 2Cl ^- / K ⁺ - carrier on the thick part of the ascending Henle loop and thereby the tubular reabsorption of these ions. Substance examples : furosemide , torasemide , bumetanide , etacrynic acid , piretanide .
• Thiazide diuretics act via several mechanisms such as the reversible inhibition of Na-Cl cotransport at the distal, luminal tubule , such as the inhibition of carbonic anhydrase and the reduction of the glomerular filtration rate . Substance examples : hydrochlorothiazide ( HCT ), chlorthalidone , xipamide , indapamide . Hydrochlorothiazide is often used as a fixed combination with other antihypertensive drugs .
• Potassium-sparing diuretics : those with a cycloamidine structure block the Na channels on the late distal tubule and on the collecting tube, thereby inhibiting Na ⁺ reabsorption, which leads to a reduced K ⁺ secretion. Substance examples : amiloride , triamterene . Potassium-sparing diuretics from the group of aldosterone antagonists, on the other hand, bind competitively to the aldosterone receptor and thereby inhibit Na ⁺ reabsorption and K ⁺ secretion. Aldosterone antagonists are particularly indicated for edema associated with ascites in connection with cirrhosis of the liver and as an additional therapeutic agent in chronic heart failure . Substance examples : spironolactone , potassium canrenoate, eplerenone .

Carbonic anhydrase inhibitors , which block proton secretion and sodium hydrogen carbonate reabsorption, are mostly used in the proximal tubular cells as well as diuretics . They are still used in ophthalmology to treat glaucoma . Substance example : acetazolamide .

Osmotic diuretics such as mannitol and sorbitol are only used in special cases . In hyperosmolar solution they bind free water intravascularly. They are used intravenously when there is a risk of kidney failure.

Plants with diuretic ingredients

There are a number of plants with diuretically active ingredients . Such are for example:

• Field horsetail ( Equisetum arvense )
• Thorny Restharrow ( Ononis spinosa )
• Large nettle ( Urtica dioica ) and the small nettle ( Urtica urens )
• Common goldenrod ( Solidago virgaurea ) and the giant goldenrod ( Solidago gigantea )
• Birch leaves ( Betula ), mainly the silver birch ( Betula pendula ; Syn .: Betula alba )
• Dandelion (taraxacum)
• Orthosiphon leaves (Orthosiphon stamineus or aristatus)

The plants mentioned are used in dried form ( tea drug ) as a component in tea mixtures for the preparation of hot water infusions (dehydration " teas "). Ready-to-use extracts, which are processed into infusion powders, tablets or drops, represent a further form of application. The effect is mild and is based on the content of certain flavonoids and / or essential oils .

Application areas (indications)

Diuretics are used in the treatment of:

• certain types of heart failure (heart failure)
• certain forms of high blood pressure
• Edema (e.g. pulmonary edema and brain edema ; not, however, e.g. in lymphedema and lipedema )
• Water retention in cirrhosis of the liver
• certain forms of renal failure
• Poisoning ( flushing of toxins in the urine)

Side effects

Diuretics are generally well tolerated and have a wide therapeutic range . Possible side effects are:

• Dehydration due to excessive water loss ( desiccosis )
• Lack of salt
  • Hyponatremia with seizures, confusion (rare), and leg cramps
  • Hypokalaemia with cardiac arrhythmias (does not apply to potassium-sparing diuretics, these can cause hyperkalemia )
• Increased tendency to thrombosis with thickened blood
• low blood pressure ( hypotension )

Diuretics are on the doping list .

Other substances with a diuretic effect

Diuretics cause diuresis. However, diuresis can also be caused by certain foods , some other drugs, numerous plants and some toxins . For example, the following also have a diuretic effect :

• alcohol
• ACE inhibitors , AT ₁ antagonists
• Xanthines such as caffeine , theobromine and theophylline

By blocking the adenosine receptors, xanthines increase the blood flow to the renal medulla , which leads to an increased production of primary urine . Despite the diuretic effect, caffeine (contained in coffee , tea , for example ) does not cause permanent dehydration, as the body counteracts it accordingly ( rebound effect ). The rebound effect also occurs with some diuretics when given as long-term therapy.

Substances that have a damaging or inhibiting influence on tubular function have a diuretic effect (e.g. also heparin and progesterone ).

literature

• Theodor Dingermann , K. Hiller, G. Schneider, I. Zündorf: Schneider drug drugs. 5th edition. Elsevier , 2004, ISBN 3-8274-1481-4 .
• Ernst Mutschler , G. Geisslinger, Heyo K. Kroemer , P. Ruth, M. Schäfer-Korting: drug effects. Textbook of Pharmacology and Toxicology , 9th edition. Wissenschaftliche Verlagsgesellschaft  mbH, Stuttgart 2008, ISBN 3-80-471952-X .

Individual evidence

1. ^ Heinrich Knauf, Ernst Mutschler : Diuretika , Urban & Schwarzenberg , 2nd edition, Munich / Vienna / Baltimore 1992, ISBN 3-541-11392-8 , p. 53.
2. ↑ K. Meng, F. Seuter: On the renal mechanism of action of diuretics , in: Karl Klütsch, Ernst Wollheim, Hans-Jürgen Holtmeier (ed.): The kidney in circulation. Georg Thieme Verlag, Stuttgart 1971, ISBN 3-13-468201-X , p. 148.
3. ↑ Quotation: "Inhibition of active transport out". Source: K. Meng, F. Seuter: On the renal mechanism of action of diuretics. In: Karl Klütsch, Ernst Wollheim, Hans-Jürgen Holtmeier (Ed.): The kidney in the circulation. Georg Thieme Verlag, Stuttgart 1971, ISBN 3-13-468201-X , p. 149.
4. ^ Robert F. Pitts: Some reflections on mechanism of action of diuretics , in: The American Journal of Medicine , Volume 17, 1958, p. 745.
5. ↑ Herbert Schwiegk (Ed.): Kidney Diseases , in: Handbook of internal medicine , 5th edition, 8th volume, 1st part, Springer-Verlag, Berlin / Heidelberg / New York 1968, p. 595.
6. ↑ Franz Volhard : The bilateral hematogenous kidney diseases . In: Gustav von Bergmann , Rudolf Staehelin (Hrsg.): Handbuch der Innere Medizin , 2nd edition, published by Julius Springer, Berlin / Heidelberg 1931, volume 6, part 1, p. 349.
7. ↑ Dietrich Höffler: Diuretic therapy in practice. Aesopus Verlag, Basel / Wiesbaden 1982, ISBN 3-87949-080-5 , p. 7.
8. ↑ See Markus Veit: Problems with the evaluation of plant diuretics. In: Journal of Phytotherapy . Volume 16, 1994, pp. 331-341; and the same: quality assurance of herbal medicines. In: Deutsche Apotheker-Zeitung . Volume 135, No. 2, 1995, pp. 159-165.
9. ↑ List of natural medicines , 15th edition, Sommer-Verlag, Teningen 1994, ISBN 3-925367-98-5 , pp. 463-477. 30 diuretics are listed here.
10. ↑ Cardiac glycosides. 2nd Edition. Beiersdorf AG , Hamburg 1975, p. 24 f.
11. ↑ Hans Joachim Gilfrich: Pharmacodynamic changes due to cardiac glycosides: What does the discharge test show? , in: Helmut Gillmann, Liv Storstein (Hrsg.): Digitalistherapie heute. Verlag for Applied Sciences, Munich 1983, ISBN 3-922251-78-1 , p. 14.
12. ^ Josef Heinzler: Brief presentation of pharmacology and toxicology , Medical Review Munich, 9th edition, Munich 1973, pp. 206-212.
13. ^ Gustav Kuschinsky , Heinz Lüllmann : Kurzes Lehrbuch der Pharmakologie und Toxikologie , 9th edition, Georg Thieme Verlag, Stuttgart / New York 1981, ISBN 3-13-368509-0 , pp. 160–167.
14. ↑ Kurt Kochsiek , Helmut Gillmann, Alfred Schrey: Diuretics for hypertension and heart failure , Urban & Schwarzenberg, Munich / Vienna / Baltimore 1984, ISBN 3-541-10891-6 .
15. ↑ "The first mercury diuretic was used to flush out edema in 1919." Source: Heinrich Knauf, Ernst Mutschler : Diuretika , Urban & Schwarzenberg, 2nd edition, Munich / Vienna / Baltimore 1992, ISBN 3-541-11392-8 , foreword on page V.
16. ↑ Doping offender leaves the Olympic village. ( Memento from February 19, 2018 in the Internet Archive ) orf.at, February 19, 2018, accessed February 19, 2018.
17. ^ Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2., revised. and exp. Edition. Wissenschaftliche Verlagsgesellschaft, Stuttgart 2005, ISBN 978-3-8047-2113-5 , p. 177 f .
18. ^ "Pharmacological possibilities for reducing the increased proximal tubular reabsorption". Quotation: F. Krück, Alfred Schrey (ed.): Diuretika III , Springer-Verlag, ISBN 3-540-16947-4 , Berlin / Heidelberg / New York 1986, p. 57.
19. ↑ diuretics; Masking agents; Doping; Prohibited Substances ( Memento of May 22, 2012 in the Internet Archive ), independent information from the National Anti-Doping Agency (NADA).
20. ↑ Coffee is better than its reputation: New results relieve the popular pick-me-up. On: Wissenschaft.de from April 5, 2005.
21. ↑ Study: Coffee does not remove water from the body. ( Memento of January 27, 2007 in the Internet Archive ).
22. ↑ Klaus Aktories, Ulrich Förstermann, Franz Hofmann, Klaus Starke: General and special pharmacology and toxicology , 10th edition, Elsevier, Urban & Fischer, Munich / Jena 2009, ISBN 978-3-437-42522-6 .
23. ↑ Hans Joachim Sarre : Kidney diseases , 4th edition, Georg Thieme Verlag, Stuttgart 1976, ISBN 3-13-392804-X , p. 430 ff.
24. ↑ After embolization of a kidney with vinyl acetate it came to the " atrophy of the tubular system at relatively well-preserved together gerückten glomeruli." Quote: Hubert Frohmüller : Experimental renal artery stenosis and high pressure , in: (ed.) Karl Klütsch, Ernst Wollheim, Hans-Jürgen Holt Meier: The kidney in circulation. Georg Thieme Verlag, Stuttgart 1971, ISBN 3-13-468201-X , pp. 211-218.
25. ↑ Hans Jahrmärker : Drugs influencing the diuresis , in: Karl Klütsch, Ernst Wollheim, Hans-Jürgen Holtmeier (ed.): The kidney in the circulation. Georg Thieme Verlag, Stuttgart 1971, ISBN 3-13-468201-X , pp. 138-147.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !