Acetazolamide proximal, loop diuretics in the loop, thiazides distal, potassium sparers in the collecting duct
Mnemonic
Follow the nephron from top to bottom:
- Proximal tubule - carbonic anhydrase inhibitors (acetazolamide). Weak, cause a normal anion gap acidosis
- Loop of Henle - loop diuretics (furosemide), blocking the Na-K-2Cl cotransporter. The most powerful. Cause hypokalaemia, hypocalcaemia, ototoxicity, gout
- Distal convoluted tubule - thiazides, blocking the Na-Cl cotransporter. Cause hypokalaemia, hyponatraemia, hypercalcaemia, hyperglycaemia, hyperuricaemia
- Collecting duct - potassium sparing: spironolactone and eplerenone (aldosterone antagonists), amiloride (ENaC blocker). Cause hyperkalaemia
- Osmotic - mannitol, acting throughout
“Loops lose calcium, thiazides keep it” is the pair most often confused, and it explains why loops are used for hypercalcaemia and thiazides for calcium stones.
Spironolactone additionally blocks androgen receptors, causing gynaecomastia; eplerenone does not.
Expansion
| Class | Site | Target | Key effects |
|---|---|---|---|
| Acetazolamide | Proximal tubule | Carbonic anhydrase | Bicarbonate loss, metabolic acidosis; weak diuretic |
| Loop diuretics | Thick ascending limb | NKCC2 | Most potent; hypokalaemia, hypocalcaemia, hypomagnesaemia, metabolic alkalosis, ototoxicity |
| Thiazides | Distal convoluted tubule | NCC | Hypokalaemia, hypercalcaemia, hyponatraemia, hyperuricaemia, hyperglycaemia |
| Amiloride | Collecting duct | ENaC | Potassium sparing |
| Spironolactone | Collecting duct | Aldosterone receptor | Potassium sparing, gynaecomastia |
| Mannitol | Whole nephron | Osmotic | Draws water into the tubule |
| SGLT2 inhibitors | Proximal tubule | SGLT2 | Glycosuric, mild natriuresis |
Two patterns to hold onto. Anything acting upstream of the collecting duct delivers more sodium distally, which drives potassium secretion and causes hypokalaemia and a contraction alkalosis. Anything acting on the collecting duct spares potassium and can cause hyperkalaemia and acidosis.
Calcium is the discriminator between loop and thiazide, and it is why thiazides are used for calcium stones and loop diuretics for hypercalcaemia.