Diuretics.
Diuretics are the clearest illustration in pharmacology that anatomy predicts pharmacology. Learn which transporter a drug blocks and where that transporter sits along the nephron, and the potency, the potassium effect and the calcium effect all follow without further memorisation.
The mechanism in one sentence
Diuretics block sodium reabsorption at a specific segment of the nephron, and the segment determines both the potency and the electrolyte side effects.
Sodium is reabsorbed progressively along the nephron, and water follows it. Loop diuretics block the sodium-potassium-two-chloride transporter in the thick ascending limb, which handles a large share of sodium reabsorption, making them the most potent group. Thiazides block the sodium-chloride cotransporter in the distal convoluted tubule, which handles less, so they are weaker but longer acting. Potassium-sparing agents act last, in the collecting duct, either by blocking the aldosterone receptor or the sodium channel it controls, which is why they conserve potassium instead of wasting it.
Members of the class
| Drug | What sets it apart |
|---|---|
| Furosemide | Loop diuretic, rapid and potent, used in fluid overload. |
| Bumetanide | Loop diuretic with more reliable oral absorption in gut oedema. |
| Bendroflumethiazide and indapamide | Thiazide and thiazide-like, used mainly in hypertension. |
| Spironolactone and eplerenone | Aldosterone receptor antagonists, potassium sparing. |
| Amiloride | Blocks the epithelial sodium channel directly, potassium sparing. |
What the class is used for
- Heart failure and fluid overload, where loop diuretics dominate
- Hypertension, where thiazides are a first-line option
- Resistant hypertension and heart failure, where spironolactone is added
- Ascites and oedema in liver disease, typically spironolactone with a loop diuretic
Side effects, derived from the mechanism
Each entry below follows from the mechanism above rather than being a separate fact. Read the middle column as the answer to the question, why would that happen.
| Effect | Why it follows |
|---|---|
| Hypokalaemia with loop and thiazide diuretics | Delivering more sodium to the collecting duct increases sodium-potassium exchange there, so potassium is lost. This is what makes concurrent digoxin dangerous. |
| Hyperkalaemia with potassium-sparing agents | The same exchange is blocked, so potassium is retained. The risk compounds with ACE inhibitors and ARBs. |
| Hyponatraemia | More characteristic of thiazides, because they impair dilution while leaving the concentrating mechanism intact. |
| Opposite calcium effects | Loop diuretics increase calcium excretion; thiazides reduce it. That is why thiazides can cause hypercalcaemia and are useful in recurrent calcium stones. |
| Ototoxicity with loop diuretics | Related to the same transporter appearing in the inner ear, and more likely with rapid intravenous administration. |
| Gout | Both loop and thiazide diuretics reduce urate excretion, raising serum urate. |
Contraindications and cautions
- Anuria, and severe electrolyte depletion until corrected
- Potassium-sparing agents in hyperkalaemia or significant renal impairment
- Caution combining any diuretic with an ACE inhibitor and an NSAID
The part you cannot derive
Spironolactone is a steroid and is not selective for the mineralocorticoid receptor, so it also binds androgen and progesterone receptors. That off-target binding, rather than anything to do with the kidney, is what causes gynaecomastia. Eplerenone was designed to be more selective and largely avoids it.
Exam traps
Calcium goes opposite ways
Loops lose calcium, thiazides keep it. Questions use this to test whether you know the site of action rather than the drug name.
Hypokalaemia plus digoxin is the classic pairing
Potassium competes with digoxin at the Na⁺/K⁺-ATPase, so a low potassium increases digoxin binding and precipitates toxicity at an unchanged dose.
Potency follows the nephron segment
Loop diuretics are stronger than thiazides because the thick ascending limb reabsorbs far more sodium than the distal tubule does.
Members of this class that get confused
Within a class, the members differ on one property at a time, and that property is what exam questions are usually built on. These pairs split cleanly.
- Amlodipine vs Nifedipine — Both are dihydropyridine calcium channel blockers acting on vascular smooth muscle, and the difference is entirely how fast they act.
- Furosemide vs Bendroflumethiazide — Furosemide blocks the sodium-potassium-two-chloride transporter in the thick ascending limb, which handles a large share of filtered sodium, making it potent.
- Spironolactone vs Eplerenone — Both block the mineralocorticoid receptor, but spironolactone is a steroid that also binds androgen and progesterone receptors, which is what causes gynaecomastia and menstrual irregularity.
Test yourself on this
Reading a mechanism and being able to retrieve it under time are different skills, and only the second one is examined. These are free and need no account.
- Cardiovascular pharmacology practice questions — 10 questions with explanations
- Digoxin toxicity and its antidote
- When to avoid NSAIDs
- Creatinine clearance calculator (Cockcroft-Gault) — free calculator with a worked example
- Milliequivalent and millimole converter — free calculator with a worked example
Common questions
What is the difference between a loop and a thiazide diuretic?
Loop diuretics block sodium reabsorption in the thick ascending limb, which handles a large share of filtered sodium, making them potent and fast. Thiazides act in the distal convoluted tubule, which handles less, so they are weaker but longer acting and better suited to hypertension.
Why do diuretics cause low potassium?
Blocking sodium reabsorption upstream delivers more sodium to the collecting duct, where it is exchanged for potassium. More exchange means more potassium lost in the urine.
Why does spironolactone cause gynaecomastia?
It is a steroid that also binds androgen and progesterone receptors, so the effect is off-target hormonal activity rather than anything to do with its diuretic action. Eplerenone is more receptor-selective and largely avoids it.
Other drug classes
Beta blockers · ACE inhibitors · Statins · Anticoagulants · Opioids · Benzodiazepines · All drug classes
Study aid only. This page is written for learning and examination practice. It is not medical advice, not clinical decision support, and must never be used to make a decision about a real patient. Always verify against your local formulary, the product literature and a qualified pharmacist. See our medical disclaimer.
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