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Low-dose spironolactone is generally very well tolerated. [62] Even higher doses of spironolactone, such as 100 mg/day, are well tolerated in most individuals. [62] Dose-dependent side effects of spironolactone include menstrual irregularities, breast tenderness, and enlargement, orthostatic hypotension, and hyperkalemia. [62]
In one study, the threshold dose by subcutaneous injection for endometrial transformation in rabbits was 0.003–0.01 mg for cyproterone acetate, 0.1–0.3 mg for drospirenone, 0.5 mg for progesterone, and 10–20 mg for spironolactone. [119]
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
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%
Low-dose aspirin therapy. Beta-blockers. Nitroglycerin. Statins and other cholesterol-lowering drugs. Calcium channel blockers. Long-acting nitrates. Endovascular surgery. Coronary artery bypass ...
Loop diuretics usually have a ceiling effect whereby doses greater than a certain maximum amount will not increase the clinical effect of the drug. Also, there is a threshold minimum concentration of loop diuretics that needs to be achieved at the thick ascending limb to enable the onset of abrupt diuresis.
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For comparison to progesterone, a 200 mg dose of oral progesterone is considered to be approximately equivalent in antimineralocorticoid effect to a 25 to 50 mg dose of spironolactone. [87] Both drospirenone and progesterone are actually weak partial agonists of the MR in the absence of mineralocorticoids. [5] [4] [65]
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