Primary hyperaldosteronism
Nadia Barghouthi, Jessica Perini in Endocrine Diseases in Pregnancy and the Postpartum Period, 2021
Mineralocorticoid receptor antagonists such as spironolactone and eplerenone are typically first-line agents in treatment of primary hyperaldosteronism. However, because spironolactone can cross the placenta, there is a concern with its use during pregnancy due to the theoretical risk of feminization of male fetuses based on animal models. Thus, mineralocorticoid receptor antagonists are not recommended for use in pregnancy and should be discontinued approximately one month before conception.23 In the limited cases of spironolactone use during pregnancy for primary hyperaldosteronism, no feminization or malformations were noted in male infants.4 There was a single case of sexual ambiguity in a female fetus in the setting of maternal use of spironolactone until the 5th month of pregnancy.30 No significant data exists regarding the use of eplerenone during pregnancy.19
Drugs and Therapeutics
James Sherifi in General Practice Under the NHS, 2023
As with many of the drugs in this account, dosages have decreased over the years as doctors have become more risk averse. IV injections of 80–160 mg were considered normal in the 1980s; today, 20–40 mg is used. Regardless of dose, the injectable formulation is now rarely used by GPs; patients with left ventricular failure tend to go directly to hospital via 999. Spironolactone—1960Oedema, Ascites, Hirsutism Spironolactone is a potassium-sparing diuretic commonly prescribed by GPs as an adjunct to loop diuretics in the management of cardiac failure, oedema, and ascites. It has now been superseded for cardiac failure by eplerenone. Adverse effects include hyperkalaemia and, rather distressing for the patient, gynaecomastia. Both resolve on cessation of the drug, which is now more commonly initiated by a cardiologist. Propranolol—1962, Atenolol 1969Hypertension, Angina, Anxiety, Migraine, Headache Sir James Black pioneered target-driven drug discovery with propranolol, the first of the β-adrenergic receptor blockers that would spawn so many others that the class became known as the ‘me-too’ drugs. There was even a generic called ‘metoprolol’!
Pharmacological therapy
ILEANA PIÑA, SIDNEY GOLDSTEIN, MARK E DUNLAP in The Year in Heart Failure, 2005
This study provides important confirmatory evidence of t he benefit of aldosterone blockade in patient s with left ventricular systolic dysfunction. The addition of eplerenone resulted in important reductions in morbidity and mortality among patients wit h acute myocardial infarction complicated by left ventricular dysfunction and heart failure. Combined with t he data from the RALES trial that showed t hat spironolactone administration was associated with a 30% reduction in all-cause mortality in patients with severe heart failure, the EPHESUS t rial supports the value of aldosterone inhibit ion in a new subset of t he heart failure syndrome.
Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability
Published in Drug Delivery, 2021
Muhammad Ayub Khan, Muhammad Mohsin Ansari, Sadia Tabassam Arif, Abida Raza, Ho-Ik Choi, Chang-Wan Lim, Ha-Yeon Noh, Jin-Su Noh, Salman Akram, Hafiz Awais Nawaz, Muhammad Ammad, Abir Abdullah Alamro, Amani Ahmed Alghamdi, Jin-Ki Kim, Alam Zeb
Eplerenone (EPL) is an aldosterone receptor antagonist and is utilized to manage hypertension and chronic heart failure (Seferovic et al., 2015). Like other BCS class II drugs, EPL also possesses low aqueous solubility and dissolution-dependent absorption with the resultant low oral bioavailability (Ozdemir et al., 2018). Therefore, its solubilizing capability needs to be enhanced for achieving efficient absorption and sufficient bioavailability. The current work is intended to develop and optimize eplerenone nanocrystals (EPL-NCs) by using a D-optimal mixture design process. EPL-NCs were prepared by using a novel bottom-up, controlled crystallization technique during freeze-drying, and the optimized formulation was subsequently studied for different physicochemical properties. The in vitro saturation solubility and dissolution profile of EPL-NCs was measured in 0.1 N HCl solution as a gastric fluid. The in vivo pharmacokinetic parameters were determined after oral administration of EPL-NCs to rats. Furthermore, a single-dose acute oral toxicity study on the developed EPL-NCs was conducted in mice for 14 days. The graphical summary of our study is presented in Supplementary Fig. 1.
Optimal cardiovascular medical therapy: current guidelines and new developments
Published in Baylor University Medical Center Proceedings, 2022
Shirley Cotty Reed, Nikita Dhir, R. Jay Widmer
Both AHA/ACC and ESC recommend the use of aldosterone antagonists (spironolactone or eplerenone) in patients with LVEF ≤35% or after MI if LVEF ≤40% with heart failure symptoms or diabetes mellitus.2,3 The RALES (Randomized Aldactone Evaluation Study) trial was the first to demonstrate a reduction in all-cause mortality (30%) in patients with heart failure and LVEF <35% with the use of spironolactone.25 Subsequent trials EPHESUS (Eplerenone Post-AMI Heart Failure Efficacy and Survival Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) investigated the use of eplerenone in heart failure with reduced ejection fraction post-MI and treatment of heart failure symptoms and demonstrated similar benefits.26,27
Effects of eplerenone on cerebral aldosterone levels and brain lesions in spontaneously hypertensive rats
Published in Clinical and Experimental Hypertension, 2020
Xue Wang, Yuhai Zhu, Shuanglin Wang, Zhuoqun Wang, Haonan Sun, Yujie He, Wei Yao
Adverse cardiovascular effects may occur in response to aldosterone escape during chronic angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy (11), which are often used to treat hypertension. As a result, mineralocorticoid receptor antagonists have been increasingly used in patients with treatment-resistant hypertension. Several studies have shown that aldosterone receptor antagonism can protect organs and vasculature without significantly lowering blood pressure (BP), which is consistent with a major role for endogenous mineralocorticoids as mediators of cardiovascular injury (12). Blocking aldosterone receptors is an important goal in the clinical treatment of patients with heart or kidney dysfunction. As a selective aldosterone receptor blocker, eplerenone has advantages such as low sex hormone-related side effetcs and has exhibited therapeutic value in preventing cardiovascular disease and associated end organ damage (13). However, whether or not it has a role in protecting brain tissue remains unclear. Thus, hypothesizing that eplerenone could alleviate the brain damage caused by hypertension is tempting. The aim of the present study was to verify the relationship between cerebral aldosterone levels and brain tissue damage of spontaneously hypertensive rats (SHRs), and to determine the effects of eplerenone on BP and in protecting brain tissue.
Related Knowledge Centers
- Steroid
- Spironolactone
- Hypertension
- Heart Failure
- Aldosterone
- Antimineralocorticoid
- Potassium-Sparing Diuretic
- Spirolactone
- Binding Selectivity
- Mineralocorticoid Receptor