A mineralocorticoid receptor antagonist (MRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors.
This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure.
Spironolactone, the first member of the class, is also used management of hyperaldosteronism: Conn’s syndrome and female hirsutism due to additional antiandrogen actions.
Most antimineralocorticoids, including spironolactone, are steroidal spirolactones.
Finerenone is a nonsteroidal antimineralocorticoid.
Mineralocorticoid receptor antagonists are diuretic drugs that work primarily on the kidneys to decrease sodium reabsorption, which leads to increased water excretion by the kidneys.
By regulating water excretion, mineralocorticoid receptor antagonists can lower blood pressure and reduce fluid around the heart.
Mineralocorticoid receptor antagonists have proven beneficial for diseases like primary aldosteronism, primary and resistant hypertension, heart failure and chronic kidney disease.
They are commonly used with other medications, such as ACE inhibitors or beta blockers.
MRA’s are a class 1 treatment for CHF and reduced ejection fraction.
In this situation, these agentwith reductions in death from any cause, death from cardiovascular causes, and hospitalization for heart failure.
Adverse effects:
Increased urination is a commonly reported, particularly during the initial phase following treatment initiation; this is mostly transient and tends to reduce with sustained treatment.
Other common side effects for antimineralocorticoid medications include nausea and vomiting, stomach cramps, diarrhoea, and significant hyperkalemia.
The pathophysiology of hyperkalemia is that these medications reduce potassium excretion.
Aldosterone is a mineralocorticoid which is synthesized and secreted from the adrenal glands.
When aldosterone is secreted from the adrenal glands, it binds to the mineralocorticoid receptor in the renal tubule cell and forms a complex.
This complex enhances transcription of specific DNA segments in the nucleus.
This leads leading to the formation of two protein transporters, Na+/K+ ATPase pump at the basolateral membrane and Na+ channel called ENaC, located at the apical membrane of the renal tubule cell.
As a result these protein transporters increase sodium reabsorption and potassium excretion in the distal tubule and the collecting duct of the kidneys.
This helps the body to maintain normal volume and electrolyte balance, increasing the blood pressure.
Mineralocorticoid receptor antagonists decrease the aldosterone effect by binding to the mineralocorticoid receptor inhibiting aldosterone, leading to higher levels of potassium in serum and increased sodium excretion, resulting in decreased body fluid and lower blood pressure.
List of mineralocorticoid receptor antagonists
Spironolactone-Heart failure, Hypertension, nephrotic syndrome, Ascites, antiandrogenic
Eplerenone-Hypertension, Heart failure, Central Serous Retinopathy
Finerenone
Potassium-sparing diuretic.
Spironolactone has shorter half-life (t1/2 = 1.3-1.4 hours) than eplerenone (t1/2 = 4–6 hours).
Eplerenone goes through rapid metabolism by the liver to inactive metabolites (t1/2 = 4–6 hours).
However, spironolactone is metabolized to three active metabolites, which give it prolonged activity (13.8 – 16. 5 hours).
Spironolactone has a long half-life.
Spironolactone is excreted 47-51% through kidneys, and is also eliminated through feces (35-41%).
The excretion of eplerenone is 67% through kidneys and 32% through feces.
The information about excretion plays a critical role when determining the appropriate doses for patients with renal and/or hepatic dysfunction.
With renal dysfunction failure to eliminate the drug through the kidneys it may accumulate in the body, causing high concentration of potassium in the blood.
Spironolactone and Eplerenone competitively block the binding of aldosterone to the mineralocorticoid receptor and hindering the reabsorption of sodium and chloride ions.
Eplerenone is a spironolactone analog with reduced adverse effects.
Eplerenone has a 20-40-fold lower affinity for the mineralocorticoid receptor than spironolactone.
Nonsteroidal nature of finerenone’s affinity toward mineralocorticoid receptors is equal to that of spironolactone and 500 times that of eplerenone, hinting that the steroidal core component of most antimineralocorticoids is not essential for mineralocorticoid receptor affinity.
Spironolactone — the first and most widely used member of this class Eplerenone — much more selective than spironolactone on target, but somewhat less potent and efficacious Finerenone — nonsteroidal and more potent and selective than either eplerenone or spironolactone
Some drugs also have antimineralocorticoid effects secondary to their main mechanism of actions: progesterone, drospirenone, gestodene, and benidipine.
In the FINEARTS-HF trial finerenone showed improvement in patients with heart failure with LVEF of 40% or greater with lower rate of worsening heart failure events in death from cardiovascular disease, than placebo.