Drug intelligence / Profile preview

chlorthalidone + spironolactone

Development stage
Unknown
Lead developer
VA Office of Research & Development
Modality
Small Molecules
Administration
Oral
01

Overview

Chlorthalidone + spironolactone is a combination therapy consisting of a thiazide-like diuretic and a mineralocorticoid receptor antagonist (MRA). Chlorthalidone acts by inhibiting sodium reabsorption in the distal convoluted tubule through the blockade of the sodium-chloride symporter, leading to increased excretion of sodium and water. Spironolactone is a competitive antagonist of the mineralocorticoid receptor, primarily in the distal tubule and collecting duct, which inhibits the action of aldosterone to promote sodium excretion while retaining potassium. This combination is specifically being evaluated for its synergistic potential in treating poorly controlled hypertension, particularly in patients with moderate to advanced chronic kidney disease (CKD). The combination aims to provide robust blood pressure lowering while mitigating the risk of hypokalemia often associated with thiazide-like diuretics. It is currently the subject of the LODESTAR trial sponsored by the VA Office of Research and Development.

Other names
chlorthalidone and spironolactonespironolactone and chlorthalidone
02

Targets

PR (Progesterone receptor)17β-HSD2 (17-beta-hydroxysteroid dehydrogenase type 2)AR (Adrenergic receptors)SLC12A3 (Thiazide-sensitive sodium-chloride cotransporter)MR (Mineralocorticoid receptor)

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