The pathogenesis of pseudohyperaldosteronism from carbenoxolone.
Carbenoxolone is a derivative of glycyrrhetinic acid used for the treatment of peptic ulcer and gastritis, with salt and water retention a very common side-effect. To investigate this drug-induced pseudohyperaldosteronism we have studied 6 male volunteers before, during and after treatment with carbenoxolone for 7 days. Serum, urinary and sweat electrolytes values were consistent with a mineralocorticoid-like effect of drug administration. PRA was suppressed, and plasma cortisol and aldosterone progressively decreased over treatment. We have also determined by radioreceptor assay the plasma levels of factors which bind to mineralocorticoid receptors in rat kidney cytosol. The levels of these factors were decreased significantly at day 3 of treatment, suggesting a local renal effect of carbenoxolone to amplify endogenous steroid action. At day 7 the radioreceptor assay values were still decreased but significantly higher than at day 3, suggesting in addition a direct mineralocorticoid effect of the drug. We conclude that the drug is initially effective by amplifying the effect of endogenous steroids, and then when the plasma concentrations of the drug or its metabolites reach a higher plasma concentration, there may also be in addition a direct mineralocorticoid-like effect.
Armanini
D
D
Istituto Semeiotica Medica, Università di Padova, Italy.
Scali
M
M
Zennaro
M C
MC
Karbowiak
I
I
Wallace
C
C
Lewicka
S
S
Vecsei
P
P
Mantero
F
F
D000328:Adult; D000450:Aldosterone / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002229:Carbenoxolone / Q000009:adverse effects*; D003600:Cytosol / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006929:Hyperaldosteronism / Q000139:chemically induced* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism / Q000502:physiology; D012083:Renin / Q000378:metabolism; D013760:Tetrahydrocortisol / Q000652:urine; D013761:Tetrahydrocortisone / Q000652:urine
D004573:Electrolytes; D008901:Mineralocorticoids; D000450:Aldosterone; D013761:Tetrahydrocortisone; D013760:Tetrahydrocortisol; D012083:Renin; D002229:Carbenoxolone; D006034:Glycyrrhetinic Acid; D006854:Hydrocortisone