Spironolactone vs eplerenone.
This pair is a lesson in what receptor selectivity is worth. The therapeutic action is essentially the same, the price is different, and the entire difference in side effects comes from off-target binding rather than from anything the drugs are meant to do.
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. Eplerenone was designed to be selective for the mineralocorticoid receptor and largely avoids those effects.
Spironolactone vs Eplerenone at a glance
| Property | Spironolactone | Eplerenone |
|---|---|---|
| Mineralocorticoid receptor | Blocks | Blocks |
| Androgen receptor | Also blocks | Minimal activity |
| Progesterone receptor | Also binds | Minimal activity |
| Gynaecomastia | Common, dose related | Uncommon |
| Potency at target | Higher | Lower, so higher doses used |
| Cost | Low | Higher |
| Hyperkalaemia risk | Yes | Yes |
Why a steroid struggles to be selective
Spironolactone is built on a steroid backbone, and the receptors for aldosterone, testosterone and progesterone are all steroid receptors with related binding sites. A molecule shaped to fit one will often fit the others, which is why the endocrine side effects are inherent to the design rather than an unlucky accident. Eplerenone modifies that backbone to reduce the fit at androgen and progesterone receptors.
Why selectivity costs potency
The structural changes that reduce off-target binding also reduce affinity for the intended receptor, so eplerenone is less potent at the mineralocorticoid receptor and is given at higher doses. This is the usual trade in drug design: selectivity is rarely free, and the cleaner molecule is often the weaker one.
What does not differ between them
Hyperkalaemia is a consequence of the intended mechanism, not of off-target binding, so it applies equally to both. Blocking aldosterone means potassium is retained regardless of how selective the block is, and the risk compounds with ACE inhibitors, ARBs and potassium supplements in either case.
Which one would the question pick?
Exams rarely ask what a drug does. They describe a patient and ask which of the two you would choose, so the scenarios below matter more than either drug monograph.
| Scenario | Pick | Why |
|---|---|---|
| Heart failure, cost a concern | Spironolactone | Effective and inexpensive, with side effects tolerated by many. |
| Gynaecomastia on spironolactone | Eplerenone | Receptor selectivity avoids the androgen effect. |
| Ascites in liver disease | Spironolactone | The established agent, often with a loop diuretic. |
Traps that catch people on this pair
Expecting eplerenone to avoid hyperkalaemia
Hyperkalaemia follows the intended mechanism and applies to both drugs equally.
Assuming the newer drug is stronger
Eplerenone is less potent at the target receptor and is dosed higher; its advantage is tolerability, not efficacy.
Common questions
What is the difference between spironolactone and 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. Eplerenone was designed to be selective for the mineralocorticoid receptor and largely avoids those effects.
Why does spironolactone cause gynaecomastia but eplerenone does not?
Spironolactone is a steroid that also binds androgen and progesterone receptors, producing endocrine effects unrelated to its diuretic action. Eplerenone was designed for selectivity at the mineralocorticoid receptor and largely avoids them.
Do both cause high potassium?
Yes. Hyperkalaemia results from blocking aldosterone, which is the intended mechanism of both drugs, so selectivity makes no difference to that risk.
Is eplerenone stronger than spironolactone?
No. It is less potent at the mineralocorticoid receptor and is given at higher doses. Its advantage is a cleaner side effect profile rather than greater efficacy.
Go deeper on the mechanism
A comparison only sticks once the shared mechanism underneath it does, because what separates two drugs is always a variation on something they have in common.
- Diuretics — the class both drugs belong to
- Cardiovascular pharmacology questions — test the distinction under time
- Digoxin toxicity and its antidote
Other comparisons
Heparin vs Warfarin · Warfarin vs DOACs · Unfractionated heparin vs Enoxaparin · Propranolol vs Atenolol · Metoprolol vs Atenolol · Amlodipine vs Nifedipine · Furosemide vs Bendroflumethiazide · Simvastatin vs Atorvastatin · All comparisons
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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