Pharmacokinetics and Pharmacodynamics of Mineralocorticoid Blocking Agents and their Effects on Potassium Homeostasis

  title={Pharmacokinetics and Pharmacodynamics of Mineralocorticoid Blocking Agents and their Effects on Potassium Homeostasis},
  author={Domenic A. Sica},
  journal={Heart Failure Reviews},
  • D. Sica
  • Published 2005
  • Biology, Medicine, Chemistry
  • Heart Failure Reviews
Spironolacotone and eplerenone are mineralocorticoid-blocking agents used for their ability to block both the epithelial and non-epithelial actions of aldosterone. Spironolactone is a non-selective mineralocorticoid receptor antagonist with moderate affinity for both progesterone and androgen receptors. The latter property increases the likelihood of endocrine side effects with spironolactone including loss of libido, menstrual irregularities, gynecomastia and impotence. Eplerenone is a next… 
Mineralocorticoid Receptor Antagonists for Treatment of Hypertension and Heart Failure.
  • D. Sica
  • Medicine, Biology
    Methodist DeBakey cardiovascular journal
  • 2015
Hyperkalemia should always be considered a possibility in patients receiving either spironolactone or eplerenone; therefore, anticipatory steps should be taken to minimize the likelihood of its occurrence if long-term therapy of these agents is being considered.
Mineralocorticoid receptor antagonists, a class beyond spironolactone--Focus on the special pharmacologic properties of eplerenone.
A Comparison of the Aldosterone‐blocking Agents Eplerenone and Spironolactone
Both spironolactone and eplerenone effectively treat hypertension and heart failure but comparisons are complicated by the deficiency of head‐to‐head trials and differences between patient populations.
The risks and benefits of aldosterone antagonists
  • D. Sica
  • Medicine, Biology
    Current heart failure reports
  • 2005
For most patients the risk of developing hyperkalemia should not dissuade the prudent clinician from use of spironolactone and eplerenone, but as enthusiasm grows for use of mineralocorticoid-blocking agents, the risks inherent to use of such drugs become more pertinent.
Eplerenone Versus Spironolactone in Resistant Hypertension: an Efficacy and/or Cost or Just a Men’s Issue?
Spironolactone has been established as the most effective add-on anti-aldosterone therapy in resistant HTN and the data on use of eplerenone continue to emerge and are quite encouraging, suggesting this agent is a preferred choice for patients developing anti-androgenic side effects like breast tenderness, gynecomastia/mastodynia and/or sexual dysfunction.
Pharmacological treatment of aldosterone excess.
Comparison of agents that affect aldosterone action.
Nonsteroidal mineralocorticoid antagonists in diabetic kidney disease
Clinical studies with a novel MRA, finerenone, and several nonsteroidal MRAs being studied for treatment in DKD are provided, showing a clear role in reducing albuminuria when used with other renin–angiotensin system blockers inDKD.


The 45-year story of the development of an anti-aldosterone more specific than spironolactone
  • J. Ménard
  • Medicine, Biology
    Molecular and Cellular Endocrinology
  • 2004
Aldosterone and aldosterone antagonism in cardiovascular disease: focus on eplerenone (Inspra).
Eplerenone (INSPRA), a selective aldosterone blocker, is currently being investigated for its efficacy and side-effect profile compared with spironolactone, which has proven to be an effective, albeit nonselective, ald testosterone receptor blocker.
Aldosterone-receptor antagonism and end-stage renal disease
Pilot safety studies with aldosterone-receptor antagonists in ESRD patients have begun, implying that spironolactone can be safely used in carefully selected and closely monitored patients.
Aldosterone and aldosterone antagonism in systemic hypertension
Eplerenone, more specific for the mineralocorticoid receptor, appears to provide all the beneficial effects of spironolactone in hypertensive patients, with the potential to modify many of the side effects related to nonspecific steroidreceptor blockade.
Efficacy of low-dose spironolactone in subjects with resistant hypertension.
Interactions of Aldosterone Antagonist Diuretics with Human Serum Proteins
Investigation of the binding mechanism of aldosterone antagonist diuretics with human serum proteins, human serum albumin and α1-acid glycoprotein as well as to identify the binding sites of the drugs on these proteins found that SP bound to site I, particularly to the warfarin region on HSA, and to the basic binding site on AGP.
Pharmacokinetics of spironolactone after a single dose: evaluation of the true canrenone serum concentrations during 24 hours.
The fraction of true canrenone rises during 24 hours, indicating thatCanrenone has a slower elimination rate than the other metabolites, and the pharmacological potency of canren one is only about 1/3 of an equivalent amount of all spironolactone metabolites.
Spironolactone: A Re-Examination
Spironolactone is useful as a diuretic in conditions such as cirrhosis and congestive heart failure, and is most commonly employed because of its potassium- and magnesium-sparing qualities.