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Contraindications of spironolactone include hyperkalemia (high potassium levels), severe and end-stage kidney disease (due to high hyperkalemia risk, except possibly in those on dialysis), Addison's disease (adrenal insufficiency and low aldosterone levels), and concomitant use of eplerenone.
However, some studies have observed increased cortisol levels with spironolactone treatment, [130] [131] possibly because of the antimineralocorticoid activity of spironolactone, which prevents negative feedback of mineralocorticoids like aldosterone on the hypothalamic–pituitary–adrenal axis (HPA axis), and thereby upregulates ...
Spironolactone and Eplerenone competitively block the binding of aldosterone to the mineralocorticoid receptor and hindering the reabsorption of sodium and chloride ions. The activity of mineralocorticoid antagonists is dependent on the presence of a y-lactone ring on the C-17 position.
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.
Aldosterone antagonists, also known as mineralocorticoid receptor antagonists: [7] Spironolactone – most widespread use, inexpensive; Eplerenone – more selective so reduced side-effects but more expensive and less potent; Finerenone – non-steroidal, more selective and potent than spironolactone and eplerenone; Canrenone – very limited use
Aldosterone is increased at low sodium intakes, but the rate of increase of plasma aldosterone as potassium rises in the serum is not much lower at high sodium intakes than it is at low. Thus, potassium is strongly regulated at all sodium intakes by aldosterone when the supply of potassium is adequate, which it usually is in hunter-gatherer diets.
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Aldosterone antagonists: spironolactone, which is a competitive antagonist of aldosterone. Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal cells, preventing sodium reabsorption.