An understanding of the pharmacology of diuretics.

Diuretics are drugs that act on the kidney to increase urine production. They can be classified by their mechanism of action into:

  • Thiazides
  • Loop diuretics
  • Potassium sparing
  • Aldosterone antagonists
  • Osmotic
  • Carbonic Anhydrase inhibitors

Common Features of Diuretics

Property Diuretics
Absorption Typically poor bioavailability (exception: acetazolamide)
Distribution Variable protein binding
Metabolism Not metabolised (exception: a small amount of frusemide is metabolised to glucuronide)
Elimination Renal elimination of unchanged drug
CVS Reduced intra and extravascular volume
Renal Any diuretic which inhibits sodium reabsorption can precipitate hypokalaemia (as a greater intra-luminal concentration of sodium results in exchange of sodium for potassium ions), hyponatraemia (as there is still a net loss of sodium), and alkalosis (from loss of hydrogen ions exchanged for sodium, or the overall raised strong ion difference).

Comparison of Diuretics

Thiazides Loop Diuretics Potassium Sparing Aldosterone antagonists Osmotic Carbonic anhydrase inhibitors
Example Hydrochlorothiazide Frusemide Amiloride Spironolactone Mannitol Acetazolamide
Site Distal tubule Loop of Henle Distal tubule Distal tubule Glomerulus Proximal tubule
Mechanism of action Inhibit Na+ and Cl- reabsorption, and increase Ca2+ reabsorption in the DCT Inhibit NKCC2, the Na+/K+/2.Cl- transport protein in the thick ascending limb, impeding the counter-current multiplier. This reduces the hypertonicity of the medulla, and subsequent water reabsorption in the collecting system. Inhibits Na+/K+ exchange pump. Weak effect. Competitive aldosterone antagonist. Aldosterone stimulates Na+ reabsorption, which in turn stimulates K+ secretion. Filtered at the glomerulus and not reabsorbed, increasing filtrate osmolarity and increases water excretion. Non-competitive carbonic anhydrase inhibition, causing a bicarbonate diuresis. There is a loss of Na+, urinary HCO3-, and a retention of H+
Resp RR due to metabolic acidosis
Cardiac Antihypertensive due to reduced plasma volume and SVR Anteriolar vasodilation, reducing SVR and preload Increases intravascular volume, increasing preload. May increase CO or result in cardiac failure.
Renal Reduced renal blood flow and GFR Increased renal blood flow and GFR Increased renal blood flow Urinary alkalinisation and diuresis. In the tubule, prevents conversion of HCO3- and H+ to CO2, causing HCO3- elimination. In the tubular epithelium, prevents conversion of CO2 to HCO3- and H+, which supplies hydrogen ions usually secreted into the proximal tubule in exchange for Na+. This causes both a retention of acid and loss of Na+ and H2O.
Metabolic Hypokalaemic, hypochloraemic alkalosis. Hyperglycaemia. Hypochloraemia, hyponatraemia, hypokalaemia, hypomagnesaemia. Occasional hyperuricaemia precipitating gout. Hyperkalaemia. Hyperkalaemia, hyponatraemia. Hyperchloraemic acidosis
Miscellaneous Blood dyscrasias Deafness, typically following large doses. More common in kidney impairment and with aminoglycoside use. Gynaecomastia and menstrual irregularity due to anti-androgenism from aldosterone antagonism


  1. Peck and Hill
  2. Rand and Dale. Chapter 24 - the kidney.
  3. Auerbac
Last updated 2017-10-08

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