Diuretics: A Complete Guide with Sites of Action

Diuretics are among the most frequently tested drug classes in pharmacology — and for good reason. Once you know where each agent acts along the nephron, their effects, uses, and adverse effects become easy to predict. Start with the map below.

1. Carbonic anhydrase inhibitors — acetazolamide

Mechanism: inhibits carbonic anhydrase in the proximal tubule, reducing H⁺ generation and bicarbonate reabsorption — a weak diuretic that causes loss of NaHCO₃.

• Uses: glaucoma (↓ aqueous humour), acute mountain sickness, alkalinisation of urine, some epilepsies.
• Adverse effects: hyperchloraemic metabolic acidosis, hypokalaemia, renal stones, paraesthesia.

2. Osmotic diuretics — mannitol

Mechanism: a freely filtered, non-reabsorbed solute that holds water osmotically in the tubule (mainly PCT and descending limb). Given IV.

• Uses: raised intracranial & intra-ocular pressure, prevention of acute renal failure, forced diuresis in poisoning.
• Adverse effects / caution: initially expands plasma volume — contraindicated in heart failure and pulmonary oedema.

3. Loop diuretics — furosemide, torsemide, bumetanide

Mechanism: inhibit the Na⁺-K⁺-2Cl⁻ (NKCC2) co-transporter in the thick ascending limb — the most efficacious (“high-ceiling”) diuretics.

• Uses: acute pulmonary oedema, heart failure, oedematous states, hypercalcaemia, and in chronic kidney disease.
• Adverse effects: hypokalaemia, metabolic alkalosis, ototoxicity (dose-related), hypocalcaemia, hyperuricaemia.

4. Thiazides — hydrochlorothiazide, chlorthalidone

Mechanism: inhibit the Na⁺-Cl⁻ (NCC) co-transporter in the distal convoluted tubule — moderately effective, with a valuable antihypertensive action.

• Uses: hypertension (first-line), mild heart failure, calcium stones (they retain Ca²⁺), nephrogenic diabetes insipidus.
• Adverse effects (the “hyperGLUC”): hyperGlycaemia, hyperLipidaemia, hyperUricaemia, hyperCalcaemia; plus hypokalaemia and hyponatraemia.

5. Potassium-sparing diuretics — spironolactone, amiloride

Mechanism: act at the collecting duct. Spironolactone antagonises aldosterone; amiloride blocks the epithelial Na⁺ channel (ENaC) directly. Weak diuretics, used mainly to conserve potassium.

• Uses: with loop/thiazides to prevent hypokalaemia, heart failure, resistant hypertension, hyperaldosteronism, cirrhosis with ascites.
• Adverse effects: hyperkalaemia; spironolactone → gynaecomastia & menstrual irregularity (anti-androgen action).

The calcium twist worth memorising

Loop diuretics cause hypocalcaemia (they lose calcium); thiazides cause hypercalcaemia (they retain it). This is exactly why thiazides are used to prevent calcium-containing kidney stones, while loops are used to treat hypercalcaemia.

Exam tip: Loop = lose calcium; thiazide = take calcium back. Both waste potassium — hence the frequent pairing with a potassium-sparing agent. Get the site of action right and every effect follows.

Quick recap

Five classes, five sites: PCT (acetazolamide) → PCT/descending limb (mannitol) → thick ascending limb (loop) → distal tubule (thiazide) → collecting duct (K-sparing). Match the drug to its segment, and the pharmacology of diuretics stops being memorisation and becomes logic.