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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]
Spironolactone is a potent antimineralocorticoid. [11] That is, it is an antagonist of the mineralocorticoid receptor (MR), the biological target of mineralocorticoids like aldosterone and 11-deoxycorticosterone. [11] By blocking the MR, spironolactone inhibits the effects of mineralocorticoids in the body. [11]
Warfarin is indicated for the prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism; [9] prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement; [9] and reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after ...
[12] [13] Due to its activity as an androgen receptor antagonist and progesterone receptor agonist, spironolactone causes adverse effects, including gynecomastia or decreased libido in males and menstrual abnormalities in females. [14] Spironolactone also causes hyperkalemia [15] and renal insufficiency. [16]
Eplerenone is a newer drug that was developed as a spironolactone analog with reduced adverse effects. In addition to the y-lactone ring and the substituent on C-7, eplerenone has a 9α,11α-epoxy group. This group is believed to be the reason why eplerenone has a 20-40-fold lower affinity for the mineralocorticoid receptor than spironolactone. [7]
The monitoring of warfarin and keeping the international normalized ratio (INR) between 2.0 and 3.0, along with avoiding over and under treatment, has driven a search for an alternative. [ 3 ] [ 14 ] A naturally occurring inhibitor of factor Xa was reported in 1971 by Spellman et al. from the dog hookworm. [ 15 ]
Spironolactone is a prodrug with a short terminal half-life of 1.4 hours. [5] [6] [7] The active metabolites of spironolactone have extended terminal half-lives of 13.8 hours for 7α-TMS, 15.0 hours for 6β-OH-7α-TMS, and 16.5 hours for canrenone, and accordingly, these metabolites are responsible for the therapeutic effects of the drug. [5] [6]
An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. [1] Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which help keep the bite area unclotted long enough for the animal to obtain blood.
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