Diuretics

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 18.12.2020

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Synonym(s)

Benzothiazines; Carboanhydrase inhibitors; Diuretic,Herbal diuretics; Loop diuretics; Osmodiuretics; Thiazide diuretics

Definition
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Group of drugs which, by inhibiting the renal reabsorption of mainly Na+, Cl- and HCO3- ions, cause increased excretion of these ions and (indirectly) of water, thereby lowering the plasma volume and reducing symptoms of congestion.

Complication(s)
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In the wash-out phase of oedema, aim for slow weight gain (max. 1kg/day). Possibly accompanying heparin therapy (low-dose-heparin), as the risk of thromboembolism is high! Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the effect of the diuretics.

Undesirable effects
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Diuretics are generally well tolerated and have a high therapeutic range. Possible side effects may include:

  • exsiccosis due to excessive water loss
  • Disturbances of the electrolyte balance
  • Metabolic disorders
  • Gastrointestinal disorders
  • Increased tendency to thrombosis
  • Hypotension
  • various immunological misreactions
  • real hypersensitivity reactions to the respective active substance

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

Loop diuretics (e.g. bumetanide, furosemide, piretanide, torasemide, etacrynic acid): reversibly inhibit the action of sodium, potassium and chloride symporters (Na+-2Cl--K+ cotransporters) located in the nephrons in the Thick Ascending Limb (TAL) at the interface between loop of Henle with the renal tubules. Furosemide is also diruetically effective at a glomerular filtrate of <5ml/min. All loop diuretics have a relatively short duration of action (<6h).

Thiazide diuretics (benzothiazines: derivatives and modifications of hydrochlorothiazide (HCT), chlortalidone, xipamide, indapamide) reversibly inhibit Na+-Cl- cotransport at the early distal luminal tubule. Furthermore, thiazide diuretics inhibit carbonic anhydrase and decrease glomerular filtration rate. In the treatment of arterial hypertension, they are usually used with other antihypertensive agents. The excretion of K+ ions increases, whereas that of Ca2+ions decreases. The effect of a thiazide diuretic can be weakened (diuretic resistance) by compensatory resorption increase in the distal.

Potassium-sparing diuretics

  • Potassium-sparing diuretics (diuretics with cycloamidine structure: amiloride, triamterene) prevent sodium reabsorption at the late distal tubule and at the collecting tube. There is decreased K+ secretion. The drugs are only weakly effective as monotherapeutics. They are often used in combination with thiazides ( e.g. hydrochlorothiazide + amiloride/triamterene).
  • Potassium-sparing diuretics (diuretics from the aldosterone antagonist family: spironolactone, potassium canrenoate, eplerenone) bind competitively to the aldosterone receptor, thereby inhibiting Na+ reabsorption and K+ secretion. Eplerenone is a selective aldosterone antagonist. Indications: oedema due to hyperaldosteronism (e.g. in liver cirrhosis with ascites); also alternative diuretic in chronic heart failure. Effect may be increased by combination with benzothiadiazines.

Carboanhydrase inhibitors(acetazolamide) block proton secretion and sodium hydrogen carbonate reabsorption, especially in proximal tubule cells. They have no therapeutic significance as diuretics. Carboanhydrase inhibitors are now only used in ophthalmology for glaucoma treatment.

Vaptans: With the vaptans, a new diuretic group has been available since 2005. The selective vasopressin receptor antagonists block the binding of arginine vasopressin to the V2 receptors of the distal parts of the nephron. This suppresses vasopressin-mediated reabsorption of water via aquaporins, resulting in increased diuresis. The first orally available representative of this new drug group is tolvaptan.

Osmodiuretics (e.g., mannitol 10-20% solution; sorbitol). Diuretic effect when administered intravenously. The substances bind water osmotically, are filtered glomerularly but not reabsorbed tubularly. Osmodiuretics are used intravenously for impending renal failure.

Herbaldiuretics: Herbal diuretics (along with synthetic chemical diuretics) have only secondary therapeutic importance. There are numerous diuretically active phytotherapeutics. For example, the following extracts from plants or their constituents have a diuretic effect: Field horsetail (Equisetum arvense), Radix levitistici (lovage root), thorny knapweed (Ononis spinosa), great nettle (Urtica dioica) and lesser nettle (Urtica urens), Common goldenrod (Solidago virgaurea) and Giant goldenrod (Solidago gigantea), Birch leaves (Betulae folium ), Dandelion (Taraxacum), Orthosiphon leaves (Orthosiphonis folium ). Herbal diuretics can be used as tea drugs. A part is available ready-made extracts (infusion powder, tablets or drops). The effect of these diuretically active phytotherapeutics is based on the content of certain flavonoids and/or various essential oils.

Other substances with diuretic action

  • Mercury diuretics (now obsolete)
  • Alcohol
  • ACE inhibitors
  • Xanthines(caffeine, theobromine and theophylline) increase renal blood flow by blocking adenosine receptors. This leads to increased formation of primary urine. Despite the diuretic effect, caffeine does not cause permanent dehydration, as the body counteracts accordingly (rebound effect).

Note(s)
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An apple-rice diet or green oat tea can also induce a slight diuresis by dietary means.

Regular monitoring of sodium, potassium, creatinine, uric acid, cholesterol and glucose is required.

Patientinformation
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Versch. Diuretics are on the doping list. The detection of the diuretic acetazolamide in a speed skater from Japan represented the first doping case at the 2018 Winter Olympics.

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Last updated on: 18.12.2020