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The trial was stopped early because the beneficial effect of spironolactone on all-cause death exceeded the prespecified discontinuation requirements. Spironolactone reduced the risk of death by 30% compared to placebo. Additionally, there was a 35% reduction in the risk of hospitalization for worsening heart failure in the spironolactone group.
[11] [185] [186] Other known but more minor metabolites of spironolactone include 7α-thiospironolactone (7α-TS), which is an important intermediate to the major metabolites of spironolactone, [17] as well as the 7α-methyl ethyl ester of spironolactone and the 6β-hydroxy-7α-methyl ethyl ester of spironolactone.
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]
However, spironolactone is metabolized to three active metabolites, which give it prolonged activity (13.8 – 16. 5 hours). Spironolactone has a long half-life and is excreted 47-51% through kidneys. Patients with chronic kidney disease therefore require close monitoring when taking the drug. Spironolactone is also eliminated through feces (35-41%
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
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.
Eplerenone may have a lower incidence than spironolactone of sexual side effects such as feminization, gynecomastia, impotence, low sex drive and reduction of size of male genitalia. [18] This is because other antimineralocorticoids have structural elements of the progesterone molecule, causing progestogenic and antiandrogenic outcomes. [ 4 ]
spironolactone eplerenone In the United States, the JNC8 (Eighth Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) recommends thiazide-type diuretics to be one of the first-line drug treatments for hypertension, either as monotherapy or in combination with calcium channel blockers , ACEis ...
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