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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 can cause hyperkalemia, or high blood potassium levels. [111] Rarely, this can be fatal. [111] Of people with heart disease prescribed typical dosages of spironolactone, 10 to 15% develop some degree of hyperkalemia, and 6% develop severe hyperkalemia. [111] At a higher dosage, a rate of hyperkalemia of 24% has been observed. [119]
Causes of edema that are generalized to the whole body can cause edema in multiple organs and peripherally. For example, severe heart failure can cause pulmonary edema, pleural effusions, ascites and peripheral edema. Such severe systemic edema is called anasarca. In rare cases, a parvovirus B19 infection may cause generalized edemas. [9]
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The condition is commonly associated with vascular and cardiac changes associated with aging but can be caused by many other conditions, including congestive heart failure, kidney failure, liver cirrhosis, portal hypertension, trauma, alcoholism, altitude sickness, pregnancy, hypertension, sickle cell anemia, a compromised lymphatic system or merely long periods of time sitting or standing ...
Other rheumatological disorders that can cause the features typical for RS3PE include late onset (seronegative) rheumatoid arthritis, acute sarcoidosis, ankylosing spondylitis and other spondyloarthropathies such as psoriatic arthropathy, mixed connective tissue disease, chondrocalcinosis and arthropathy due to amyloidosis.
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Spironolactone, the first member of the class, is also used in the management of hyperaldosteronism (including Conn's syndrome) and female hirsutism (due to additional antiandrogen actions). Most antimineralocorticoids, including spironolactone, are steroidal spirolactones. Finerenone is a nonsteroidal antimineralocorticoid.