Experience with the Use of an Aldosterone Antagonist in Selected Hypertensive Patients

Abstract

A number of investigators have evaluated the antihypertensive potency of spironolactone in both benign and accelerated hypertension and have found a generally small magnitude of response, somewhat comparable to the thiazide diuretics.1-5 This study was undertaken, originally, to demonstrate a possibly enhanced antihypertensive effect of spironolactone when administered to a. group of hypertensive patients showing evidence of secondary aldosteronism. Our attempt to cull such a group of patients with hyperaldosteronism from a pre-selected group of hypertensives with hypokalemia produced a disappointingly low yield. In addition to blood pressure response, the effect of spironolactone on renal function, serum potassium and carbon dioxide content have been studied. METHODThorough screening of our hypertension clinic (consisting of 102 patients) for non-thiazide induced hypokalemia (serum potassium of less than 4.0 Meq./L mean of 3 determinations) provided only six subjects. These six patients comprised the study group and it was not known until following the completion of the study which members, if any, had increased urinary aldosterone excretion levels. Six patients with an equivalent degree of hypertension were selected as a control group and differed from the study group by the presence of normokalemia. One member of the control group was subsequently discarded upon learning that he had failed to take the medication as prescribed. Both groups received spironolactone in doses of 300 mg daily (75 mg four times a day) over a four week period.Patients were seen every two weeks by one of the authors. Interval history and brief physical examination were done and laboratory tests carried out. Patients were instructed at each visit to take their medication, usual exercise and adhere to a minimum of six grams of salt (NaCI) intake. Medication fidelity was checked only by counting remaining tablets. Salt intake was confirmed by 24 hour urine sodium content.

Addition of Spironolactone in Patients With Resistant Arterial Hypertension (ASPIRANT)

“…The maximal hypotensive effect of spironolactone requires 3 to 4 weeks to be fully expressed in patients with mild hypertension 28 and 7 weeks in patients with resistant hypertension. 21 Therefore, we feel that the designed length of our trial, 8 weeks, was sufficient for the full effect of spironolactone to show.…”

Spironolactone Management of Resistant Hypertension

“…15 The maximal blood pressure response to spironolactone is achieved at 3-4 weeks, and the effect may persist for a week after discontinuing treatment, which can be attributed to the presence of active metabolites. 16,17 Spironolactone undergoes hepatic metabolism to active metabolites through deacetylation, dethiolation, and thiomethylation. 18, 19 The most significant metabolites include 7-α-thiomethylspirolactone (TMS), canrenone, and 6-β-hydroxy-7-α-thiomethylspirolactone (HTMS).…”

Pharmacokinetics and Pharmacodynamics of Mineralocorticoid Blocking Agents and their Effects on Potassium Homeostasis

“…This differs in resistant hypertension where low doses of spironolactone (25-50 mg/day) in addition to conventional therapies can significantly reduce BP [29]. The maximal hypotensive effect of spironolactone oftentimes requires 3 to 4 weeks to be fully expressed [32] and may persist for 1 to 2-weeks following its discontinuation [33].…”