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Hyperkalemia can occur following an overdose of spironolactone, and this is especially so in people with decreased kidney function. [8] Spironolactone has been studied at extremely high oral doses of up to 2,400 mg per day in clinical trials. [107] [168] Its oral median lethal dose (LD 50) is more than 1,000 mg/kg in mice, rats, and rabbits. [8]
Spironolactone has been identified as an inhibitor of NRG1‐ERBB4 signaling. [142] Spironolactone has been found to act as a potent inhibitor of the pannexin 1 channel, and this action appears to be involved in its antihypertensive effects independently of MR antagonism. [143] Spironolactone has been found to block hERG channels. [144]
A mineralocorticoid receptor antagonist (MRA or MCRA) [1] 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 .
Aldosterone binds to aldosterone receptors (mineralocorticoid receptors) increasing sodium reabsorption in an effort to increase blood pressure and improve fluid status in the body. When excessive sodium reabsorption occurs, there is an increasing loss of K + in the urine and can lead to clinically significant decreases, termed hypokalemia .
Aldosterone receptor antagonists, also known as mineralocorticoid receptor antagonist (MRA) can lower blood pressure by blocking the binding of aldosterone to the mineralocorticoid receptor. Spironolactone and eplerenone are MRAs that causes a block in the reabsorption of sodium, resulting in a decrease in blood pressure. [45] [46] eplerenone
Spirolactones are a class of functional group in organic chemistry featuring a cyclic ester attached spiro to another ring system. The name is also used to refer to a class of synthetic steroids, called steroid-17α-spirolactones, 17α-spirolactosteroids, or simply 17α-spirolactones, which feature their spirolactone group at the C17α position.
Spironolactone works by blocking a hormone in the body called aldosterone. This hormone holds onto sodium; by blocking it, it helps the kidneys flush salt and water out of the body to lower blood ...
Spironolactone has become a standard therapy for reducing mortality and morbidity in patients with severe heart failure with reduced ejection fraction. [ 2 ] [ 3 ] The RALES trial has then paved the way for further studies on the role of aldosterone antagonists in heart failure and other cardiovascular conditions.
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