Diuretics
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 | 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 | |
|---|---|---|---|---|---|---|
| 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 | 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-androgynism from aldosterone antagonism |
References
- 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.