Mineralocorticoid Receptor Antagonists in Primary Aldosteronism

Abstract

Background:Primary aldosteronism is the most common causes of secondary hypertension. Patients suffering from this clinical syndrome have an increased cardiovascular risk and target organ damage. Mineralocorticoid receptor antagonists are the optimal pharmaceutical option for the management of such patients.Objectives:The study aimed to assess the effects of mineralocorticoid receptor antagonist in the treatment of patients with primary aldosteronism.Method:We conducted an in-depth review of the literature and comprehensive identification of the clinical studies investigating the efficacy of mineralocorticoid receptor antagonists in individuals with primary aldosteronism.Results:Mineralocorticoid receptor antagonists result in significant improvement in blood pressure and serum potassium level among patients with primary aldosteronism. Moreover, mineralocorticoid receptor antagonists reverse left ventricular hypertrophy, albuminuria, and carotid intima-media thickness. However, a high risk for atrial fibrillation remains among subject with primary aldosteronism in such agents.Conclusion:Mineralocorticoid receptor antagonists are recommended as the first-line treatment in patients with bilateral primary aldosteronism. In patients with unilateral aldosterone-producing adenoma, adrenalectomy should be preferred. However, existing data presents significant limitations and is rather inconclusive. Future randomized control trials are required in order to illustrate the field.

Novel antihypertensive action of rutin is mediated via inhibition of angiotensin converting enzyme/mineralocorticoid receptor/angiotensin 2 type 1 receptor (ATR1) signaling pathways in uninephrectomized hypertensive rats

“…Primary aldosteronism is the most common cause of secondary hypertension (Satoh et al, 2019). Hence, patients suffering from primary aldosteronism have an increased propensity to develop cardiovascular disease conditions and target organ damage (Stavropoulos et al, 2018).…”

“…Primary aldosteronism is the most common cause of secondary hypertension (Satoh et al., 2019). Hence, patients suffering from primary aldosteronism have an increased propensity to develop cardiovascular disease conditions and target organ damage (Stavropoulos et al., 2018). Together, mineralocorticoid receptor antagonists have opened a novel therapeutic window for the management of patients with secondary/ resistant hypertension (Faulkner & Belin de Chantemèle, 2019; Imprialos et al., 2018; Sato, 2019).…”

Adrenal artery ablation for primary aldosteronism without apparent aldosteronoma: An efficacy and safety, proof‐of‐principle trial

“…Currently, there are no perspective randomized control trials on long‐term effect of MR antagonists. Several studies have shown that high‐dose MR antagonist therapy causes gynecomastia, mastodynia, and hyperkalemia commonly occurred in patients treated with spironolactone 11,13 . Other nonendocrine and adverse effects include muscle cramps and nonspecific neuropsychiatric symptoms such as fatigue and general weakness 12 .…”

“…Currently, mineralocorticoid receptor (MR) antagonists and laparoscopic adrenalectomy are the principal treatments for PA. However, recent studies showed that long‐term MR antagonist therapy did not reduce the risk of cardiometabolic events and death in PA patients with persistent renin suppression, 7‐9 and high dose of MR antagonist likely causes side effects 10‐13 . Laparoscopic adrenalectomy is recommended for patients with aldosterone‐producing adenoma (APA) or unilateral adrenal hyperplasia 1 .…”

Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders

“…The degradation of ERCC3 mediated by ZL-12A resembled a pharmacological effect reported previously for the sterol derivative spironolactone in a drug repositioning screen for inhibitors of NER. 52 Spironolactone is an antihypertensive drug that acts as a mineralocorticoid receptor antagonist, 53 and the molecular mechanism by which it promotes ERCC3 degradation has remained elusive but has been assumed to occur indirectly through binding another protein target. 54−56 While only limited SAR information is available for spironolactone-mediated ERCC3 degradation, we noted that spironolactone analogues lacking an electrophilic thioacetyl group are inactive.…”