Potassium-Sparing, Osmotic & Carbonic-Anhydrase Diuretics
Loops and thiazides have one nagging flaw: they flush away potassium. The fix is a class of diuretics that does the opposite — it holds potassium in. One of them also, surprisingly, treats acne and grows breasts on men; another shrinks a swollen brain; a third stops mountain sickness. Three small classes, each with a party trick that reveals exactly where and how it works on the kidney.
A heart-failure patient on furosemide keeps turning up with low potassium — cramps, fatigue, and a worrying tendency to irregular heartbeats. Rather than just handing him potassium tablets forever, his doctor adds a second diuretic: spironolactone. Now his potassium holds steady, and — importantly — this particular add-on also helps him live longer. It's a diuretic that KEEPS potassium instead of dumping it, and it works at the very last stretch of the kidney tubule. That's our entry into three specialist diuretic classes.
Potassium-sparing diuretics
These act at the collecting duct and keep potassium in. At the very end of the tubule (the collecting duct), the kidney reabsorbs a little more sodium in exchange for excreting potassium — and this final step is controlled by aldosterone. Potassium-sparing diuretics block this step, so the body loses a little sodium while KEEPING potassium. There are two ways to do it. Aldosterone antagonists — spironolactone and eplerenone — block the aldosterone receptor itself; ENaC blockers — amiloride and triamterene — plug the sodium channel directly. Because they're weak diuretics on their own, they're mostly used ALONGSIDE a loop or thiazide, to offset the potassium loss those cause.
Spironolactone is more than a diuretic. Blocking aldosterone improves survival in heart failure (so it's a 'pillar' drug, not just a water pill) and treats primary aldosterone excess (Conn's syndrome), resistant hypertension, and the fluid of liver cirrhosis. But because it also blocks androgen (male hormone) receptors, it's used for acne and unwanted hair in women — and, as a side effect in men, it can cause breast enlargement (gynaecomastia). Eplerenone is a more selective cousin that avoids that hormonal effect. The shared danger of all these drugs is the opposite of loops: too MUCH potassium (hyperkalaemia).
- Potassium-sparing diuretics act at the collecting duct and KEEP potassium (risk: hyperkalemia).
- Aldosterone antagonists (spironolactone, eplerenone) block the aldosterone receptor.
- ENaC blockers (amiloride, triamterene) plug the sodium channel; often added to a loop/thiazide.
- Spironolactone also improves heart-failure survival and can cause gynecomastia (eplerenone doesn't).
Osmotic diuretics: mannitol
Osmotic diuretics work by physics, not by blocking a transporter. Mannitol is a sugar that the kidney filters but cannot reabsorb, so it stays in the tubule and drags water out osmotically. Its special uses reflect that it pulls water out of tissues: reducing raised pressure inside the skull (cerebral oedema) and inside the eye (acute glaucoma). One caution: before it reaches the kidney, mannitol briefly EXPANDS the blood volume by pulling water into the bloodstream — which can tip a patient with heart failure or pulmonary oedema into worse fluid overload, so it's avoided there.
Carbonic-anhydrase inhibitors: acetazolamide
Acetazolamide blocks carbonic anhydrase in the proximal tubule, so the kidney can't reabsorb bicarbonate — bicarbonate (and sodium and water) are lost in the urine. It's a weak diuretic, but that bicarbonate loss makes it useful in specific situations: it lowers the fluid pressure inside the eye (glaucoma), treats altitude (mountain) sickness by causing a mild acidosis that stimulates breathing, and can correct a metabolic alkalosis. Its main side effect is exactly that: a metabolic acidosis from losing bicarbonate.
Combining a potassium-WASTING diuretic (loop or thiazide) with a potassium-SPARING one is a classic balancing act: the loss from one offsets the retention of the other, keeping potassium steady. But watch the extremes — add too much potassium-sparing effect (or a RAAS blocker, which also raises potassium) and you can swing into dangerous hyperkalaemia. Potassium is the number you track whenever you touch a patient's diuretics.
- Adding a potassium-sparing diuretic (or RAAS blocker) without checking potassium. Risk of hyperkalemia.
- Giving mannitol in heart failure/pulmonary edema. Its initial volume expansion worsens overload.
- Forgetting spironolactone causes gynecomastia (use eplerenone if that's a problem).
- Overlooking that acetazolamide causes a metabolic acidosis (loss of bicarbonate).
Which diuretic RETAINS potassium and improves heart-failure survival?
- Potassium-sparing diuretics (spironolactone/eplerenone, amiloride) act at the collecting duct and keep potassium.
- Spironolactone improves HF survival but can cause gynecomastia; the shared risk is hyperkalemia.
- Mannitol (osmotic) pulls water out — for cerebral edema & glaucoma; avoid in HF.
- Acetazolamide (carbonic-anhydrase) loses bicarbonate — glaucoma & altitude sickness; causes acidosis.
- Katzung BG. Basic & Clinical Pharmacology — Diuretic Agents (K-sparing, osmotic, carbonic-anhydrase inhibitors).
- Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics — Diuretics.
- Rang HP, Dale MM, et al. Rang & Dale's Pharmacology — The kidney & diuretics.
- Guyton & Hall Textbook of Medical Physiology — Renal handling of sodium, potassium & bicarbonate.
- Whalen K. Lippincott Illustrated Reviews: Pharmacology — Diuretics.
