Spironolactone MOA

[Burnt Almonds]

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I've been trying to figure out exactly what enzyme or receptor spironolactone inhibits. I saw somewhere that it inhibits 11Beta-hydroxylase but then wouldn't that lead to decreased cortisol also or is there something more selective going on? Also, at 11B-hydroxylase, haven't you already synthesized 11-deoxycorticosterone which still has aldosterone properties?

#clueless

 

[zhopv10]

The main MOA is antagonism at the mineralicorticoid receptor, however it does have action at the 11 beta hydroxylase, the 17,20 something lyase and a couple others. It is also a weak androgen receptor blocker and progesterone agonist. Interestingly the 11B hydroxylase has paradoxically increased cortisol levels clinically, this is due to decreased feedback at the HPA axis and it just rams more cortisol through basically. Main things tho are the mineralicorticoid receptor antagonism (what mediates diuretic effect and prevents aldosterone mediated remodeling of the heart in HF) and the androgen receptor antagonism (gynecomastia etc).


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