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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.
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%
[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]
Subsequently, if dual therapy is required to use an ACEi in combination with either a calcium channel blocker or a (thiazide) diuretic. Triple therapy is then of all three groups and should the need arise then to add in a fourth agent, to consider either a further diuretic (e.g. spironolactone or furosemide), an alpha-blocker or a beta-blocker ...
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. [1] [2] This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.
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Loop diuretics are 90% bonded to proteins and are secreted into the proximal convoluted tubule through organic anion transporter 1 (OAT-1), OAT-2, and ABCC4.Loop diuretics act on the Na +-K +-2Cl − symporter (NKCC2) in the thick ascending limb of the loop of Henle to inhibit sodium, chloride and potassium reabsorption.
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