• Clinical science

Diuretics

Abstract

Diuretics are a group of drugs that induce increased production of urine. Depending on the class, diuretics act on different renal structures and lead to varying changes in the volume and composition of urine as well as electrolyte balance. Some of these effects can be used to treat disorders like hypercalcemia, hypocalcemia or hyperaldosteronism. The most commonly used diuretics with a pronounced diuretic effect are thiazides, loop diuretics, and potassium-sparing diuretics. Osmotic diuretics and carbonic anhydrase inhibitors are used in acute settings to lower intracranial and/or intraocular pressure (e.g., cerebral edema, acute glaucoma). The most important side effects of most diuretics include volume depletion and excessive changes in serum electrolyte levels (particularly of sodium and potassium) which increases the risk for cardiac arrhythmias.

Overview of diuretics

Main characteristics and mechanisms Water elimination Effects on serum
pH Na+ K+ Ca2+
Thiazide diuretics
  • Inhibition of Na+-Cl--cotransporters in the early distal tubule
  • Effects compared to loop diuretics
    • Greater loss of potassium
    • Reduced effectiveness if GFR < 30 mL/min
↓*

Loop diuretics

  • Inhibition of Na+-K+-2Cl--cotransporters in the thick ascending loop of Henle
↑↑ ↓*

Potassium-sparing diuretics

(↑) ↓*

Osmotic diuretics

  • Effect the entire tubule, but predominantly act on the straight segment of the proximal tubule and the descending loop of Henle
  • ↑ Blood and tubular fluid osmolarityurine flow, ↓ intracranial/intraocular pressure
↑↑

Variable (see “osmotic diuretics” below)

Carbonic anhydrase inhibitors

(↑) (↓) (↓)
*Most diuretics promote saluresis and thereby increase the volume of urine

References:[1][2][3][4][5]

Thiazide diuretics

Agents

Mechanism of action

Side effects

Thiazide diuretics may be combined with potassium-sparing diuretics (e.g., aldosterone receptor antagonists) to avoid hypokalemia!

Indications

Contraindications

References:[1][6][7][2][8][9][10][11][12]

Loop diuretics

Agents

Mechanism of action

  • Blockage of Na+-K+-2Cl--cotransporters in the thick ascending loop of Henle
    • Concentration gradient between renal medulla and cortex diminishes over time → urine cannot be concentrated any more → diuresis
    • ↓ Reabsorption of Ca2+ and Mg2+
  • ↑ PGE release
    • Dilation of renal afferent arterioles → diuresis
    • General venodilation (rapid venous pooling) → ↓ cardiac preload

Loops lose calcium!

Side effects

Hypokalemia and/or hypomagnesemia can lead to life-threatening arrhythmias!

Indications

During forced diuresis, the increased risk of hypokalemia and hypovolemia makes rigorous monitoring necessary!

Contraindications

Furosemide Torsemide Bumetanide Ethacrynic acid
Anuria
  • Yes
  • Yes
  • Yes
  • Yes
Sulfonamide hypersensitivity
  • Yes
  • Yes
  • Yes
  • No
Hepatic coma or severe electrolyte depletion
  • No
  • No
  • Yes
  • No

History of severe watery diarrhea (caused by the drug)

  • No
  • No
  • No
  • Yes

Pharmacokinetics

Furosemide Torsemide Bumetanide Ethacrynic acid
Bioavailability
  • ∼ 50%
  • ∼ 80%
  • 80–100%
  • ∼ 100%
Duration of action
  • PO: 6–8 hours
  • IV: 2 hours
  • PO: 6–8 hours
  • PO: 4–6 hours
  • PO: 6–8 hours
  • IV: 2–4 hours

References:[1][2][13][14][15][16][17][18][19][20][21][22]

Potassium-sparing diuretics

Agents

Mechanism of action

Although the molecular pathways differ, both types of potassium-sparing diuretics have very similar clinical effects.

Side effects

Indications

Contraindications

Spironolactone Eplerenone Triamterene Amiloride
Anuria/renal insufficiency
  • Yes
  • Yes
  • Yes
  • Yes
Pre-existing hyperkalemia
  • Yes
  • Yes
  • Yes
  • Yes
Addison's disease
  • Yes
  • Yes
  • No
  • No
Other

References:[1][7][10][23][24][25][26][27][28]

Osmotic diuretics

Agents

Mechanism of action

  • No absorption into cells intravascular binding of water → ↓ intracranial/intraocular pressure
  • Glomerular filtration throughout the entire tubule without reabsorption → ↑ tubular fluid osmolarityurine flow
  • No saluresis

Side effects

  • Dehydration
  • Initial cardiac volumetric strain
  • Metabolic and electrolyte imbalances

Indications

Contraindications

References:[1][3][29][30][31][32][33]

Carbonic anhydrase inhibitors

Agents

Mechanism of action

Side effects

Indications

Contraindications

References:[1][34][35]