Converging Indications of Aldosterone Antagonists (Spironolactone and Eplerenone): A Narrative Review of Safety Profiles

Abstract

The converging clinical effectiveness of mineralocorticoid receptor antagonists (MRAs) Spironolactone and Eplerenone has made their safety profiles/cost-effectiveness key determinants of "agents of choice" across a broad range of clinical indications. The clinical biology of the aldosterone molecule and its range of effects in varied organ systems have been well elucidated from recent mechanistic and systematic studies. Clinical experience with Spironolactone is well established, as is its adverse effects profile. The range of adverse effects experienced with Spironolactone subsequently led to its modification and synthesis of Eplerenone. Recent published reports have confirmed lower prevalence rates of sex-related adverse effects attributable to Eplerenone compared to Spironolactone. There is, however, not much to choose between these agents in regards to other adverse effects including hyperkalemia and kidney failure. As was the experience with Spironolactone, as more robust observational data on Eplerenone accrues, it is possible that the real-life experience of its adverse profile may be discordant with that reported by randomized controlled clinical trials (RCTs). In addition, its metabolism by the vulnerable and highly polymorphic cytochrome dependent pathway also makes it susceptible to various drug interactions. The potential implication of the latter (including morbidity and mortality) may take years to evolve.

Mineralocorticoid Antagonists in the Treatment of Central Serous Chorioretinopathy: A Comparative Analysis

“…These findings corroborate previous clinical data of MR antagonists in other medical conditions, particularly systemic hypertension and heart failure [8,9,10,11]. Eplerenone has been associated with fewer side effects than spironolactone in multiple reports evaluating its use, and this has been attributed to its higher selectivity for the aldosterone receptor [7].…”

“…Studies have suggested a significant increase in side effects with chronic MR antagonist exposure, even with eplerenone (up to 47% in one study), emphasizing its judicious use and need for tapering upon clinical stability [8,9,10,11]…”

Synthetic Applications of the Parkins Nitrile Hydration Catalyst [PtH{(PMe2O)2H}(PMe2OH)]: A Review

“…Thus, as shown in Scheme 14, performing the reaction in a refluxing ethanol/water (1:1 v/v) mixture, and using a very low catalyst loading of 0.0001 mol%, atenolol could be selectively obtained in 93% yield [64]. The steroidal compound eplerenone (60) is an orally-active aldosterone antagonist featuring a canrenone-type structure that is also used for the treatment of hypertension and heart failure [65,66]. The synthesis of 60 has been the subject of several patents.…”

The Metabolic Effects of Mineralocorticoid Receptor Antagonists in Heart Failure Patients

“…Eplerenone is the first of a new class of drugs known as selective aldosterone receptor antagonists in minimal manner blocked steroid receptors, and thereby minimizing many of the hormonal side effects seen with spironolactone [27]. Overall eplerenone has been demonstrated better profile of safety and tolerability than spironolactone [28]. The antihypertensive efficacy of both drugs are probably similar, but eplerenone shown a significant renoprotective effect in diabetic patients with hypertension [29].…”