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:
- Loop diuretics
- Potassium sparing
- Aldosterone antagonists
- Carbonic Anhydrase inhibitors
Common Features of Diuretics
|Absorption||Typically poor bioavailability (exception: acetazolamide)|
|Distribution||Variable protein binding|
|Metabolism||Generally not metabolised. Key exceptions: Spironolactone is extensively metabolised with active metabolites, and 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|
|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||Arteriolar vasodilation, reducing SVR and preload||Increases intravascular volume, increasing preload. May increase CO or result in cardiac failure.|
|CNS||↓ ICP||↓ IOP, ↓ ICP|
|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|
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
- Rang HP, Dale MM, Ritter JM, Flower RJ. Rang and Dale's Pharmacology. 6th Ed. Churchill Livingstone.
- Auerbach. Wilderness Medicine. Sixth Edition.