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At least 235 records · Page 13Linked to original sources
PubMed2000

Low-dose adjunctive spironolactone in the treatment of acne in women: a retrospective analysis of 85 consecutively treated patients.

BACKGROUND: Despite advances in acne therapy in recent years, treatment failures are common, especially in adult women. Spironolactone, an established androgen receptor blocker, is successful in treating adult women with acne, but side effects are common at the doses reported in published studies to date. OBJECTIVE: The purpose of this study was to assess the therapeutic effect and tolerance of low doses of spironolactone used alone or as an adjunct in the treatment of acne in adult women. METHODS: Records were reviewed from 85 women with acne treated consecutively with spironolactone 50 to 100 mg/day, administered either as single-drug therapy or as an adjunct to standard therapies. The maximum length of treatment was 24 months. RESULTS: Clearing of acne occurred in 33% of patients treated with low doses of spironolactone; 33% had marked improvement, 27.4% showed partial improvement, and 7% showed no improvement. The treatment regimen was well tolerated, with 57.5% reporting no adverse effects. CONCLUSION: Spironolactone can be used in low doses as a single drug or as an adjunct to standard acne therapies in women with adult acne. When used in this fashion, treatment outcomes are favorable, and the drug is well tolerated.

Acne Vulgaris↗
PubMed2000

Effect of spironolactone and its metabolites on contractile property of isolated rat aorta rings.

Spironolactone and its active metabolites canrenone and potassium canrenoate are normally used as antihypertensive drugs. Although they are classified as antagonists of aldosterone, their mechanism of action cannot be ascribed solely to the regulation of ion transport in the distal tubule of nephrons. Here we have evaluated the effects of spironolactone, canrenone, and potassium canrenoate on contractile properties of isolated rat aorta rings. Spironolactone (1-300 microM), canrenone (1-300 microM), and potassium canrenoate (0.01-10 mM), in a concentration-dependent manner, relaxed rat aorta rings precontracted with phenylephrine (1 microM) or KCl (40 mM). These relaxant effects were not affected by prior treatment with either aldosterone (100 microM), glibenclamide (10 microM), or tetraethylammonium (10 mM), excluding the possibility that these drugs can be involved in either the nongenomic effect of aldosterone or on activation of potassium channels. Spironolactone and canrenone at concentrations of 30 and 100 microM, but not at 10 microM, and potassium canrenoate at concentrations of 0.3 and 1 mM, but not at 0.1 mM, significantly inhibited the phenylephrine (0.001-3 microM) concentration-response curve. Conversely, all tested concentrations of spironolactone (10, 30, and 100 microM), canrenone (10, 30, and 100 microM), and potassium canrenoate (0.1, 0.3, and 1 mM) significantly inhibited the concentration-response curve induced by cumulative concentrations of KCI (10-80 mM). Because both phenylephrine- and KCl-induced contractions imply an intracellular Ca2+ influx, we suggest that these drugs could act through an inhibition of voltage-dependent Ca2+ channels.

Animals↗
PubMed2004

Effects of AT1 receptor antagonist and spironolactone on cardiac expression of ET-1 mRNA in SHR-SP/Izm.

Angiotensin II stimulates and angiotensin-converting enzyme inhibitor decreases endothelin-1 expression. Effects of the angiotensin-type 1 antagonist (angiotensin receptor blocker) on tissue expression of endothelin-1 in hypertension remained unknown. We investigated the effects of angiotensin-type 1 antagonist with and without co-administration of the aldosterone receptor antagonist spironolactone on cardiac expression of endothelin-1 mRNA. Angiotensin receptor blocker (candesartan, 1.0 mg/kg per day) was orally administered to male spontaneously hypertensive stroke-prone rats/Izm from 4 weeks of age for 4 weeks, 12 weeks and 28 weeks (angiotensin receptor blocker group). Lowdose spironolactone (10 mg/kg per day, s.c.), which does not affect blood pressure, was co-administered with angiotensin-type 1 antagonist for 28 weeks (angiotensin-type 1 antagonist + spironolactone group). Cardiac expression of endothelin-1 mRNA was determined. In the angiotensin receptor blocker group, although cardiac expression of endothelin-1 mRNA was significantly decreased after 4 weeks of treatment, it was significantly increased after 12 weeks and 28 weeks of treatment. In the angiotensin receptor blocker + spironolactone group, while systolic blood pressure did not show a further decrease from that in the angiotensin receptor blocker group, cardiac expression of endothelin-1 mRNA was decreased to the level in the untreated group. These results suggest that effects on endothelin-1 expression could modify the cardioprotective effects of angiotensin receptor blocker. Coadministration of angiotensin receptor blocker with low-dose spironolactone is recommended for further cardioprotection via suppression of endothelin-1 expression.

Administration, Oral↗
PubMed2004

Prevention of renal fibrosis by spironolactone in mice with complete unilateral ureteral obstruction.

PURPOSE: Recent data suggest that aldosterone directly mediates cardiac fibrosis and hypertensive nephrosclerosis. We conducted experiments to determine whether administration of spironolactone, a mineralocorticoid receptor antagonist, reduced renal fibrosis in an experimental model of obstructive uropathy. MATERIALS AND METHODS: Complete unilateral ureteral obstruction (UUO) was created surgically in 8 to 10-week-old male C57BL/6 mice by placing sutures around the right ureter. Spironolactone (50 mg/kg/daily) or 1% dimethyl sulfoxide vehicle was administered by subcutaneous injection for 1 to 2 weeks, and renal fibrosis was assessed by measuring trichrome staining and type I collagen deposition in the kidney. RESULTS: UUO lasting 1 week was associated with minimal parenchymal damage and spironolactone had no demonstrable effect. In contrast, administration of the mineralocorticoid antagonist (8 mice) for a 2-week period significantly reduced renal fibrosis in the obstructed kidney, compared to mice given the dimethyl sulfoxide vehicle (9). The beneficial effect of spironolactone treatment was not associated with any changes in serum potassium or aldosterone concentration, or urinary concentrations of sodium or potassium. CONCLUSIONS: Administration of spironolactone reduced renal fibrosis in mice with UUO. These findings suggest that clinical trials are warranted to determine the efficacy of aldosterone antagonists in conjunction with angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers as renoprotective agents in patients with obstructive uropathy.

Animals↗
PubMed1991

Adequacy of twice daily dosing with potassium chloride and spironolactone in thiazide treated hypertensive patients.

1. The effects of 4-6 weeks treatment with placebo, potassium chloride 32 mmol 12 hourly, and spironolactone 25 mg 12 hourly upon the plasma potassium concentration-time profile were examined in hypertensive patients taking bendrofluazide 5 mg daily. 2. When compared with placebo, potassium chloride increased peak plasma potassium concentration (P less than 0.05), 12 h AUC for plasma potassium (P less than 0.1), and 12 h urine potassium excretion (P = 0.002). Spironolactone increased peak plasma potassium concentration (P less than 0.05), and 12 h AUC for plasma potassium (P less than 0.05), compared with placebo values. 3. Potassium chloride and spironolactone did not differ significantly in any respect other than 12 h urine potassium excretion. The 12 h AUC for plasma potassium was 35% larger with spironolactone than potassium chloride (not significant). 4. With both active drugs peak plasma potassium was observed 2-3 h after dosing, and efficacy tended to wane towards 12 h. However, variability of plasma potassium within the dose interval was not increased markedly, and 12 hourly dosing is probably satisfactory for both potassium chloride and spironolactone at the doses studied.

Adult↗
PubMed2004

Tolerability of spironolactone in patients with chronic heart failure -- a cautionary message.

AIM: To assess how well heart failure patients tolerate spironolactone in routine clinical practice. DESIGN: Retrospective analysis of 226 patients attending a specialist heart failure clinic. RESULTS: One hundred and thirty of 226 (57.5%) patients tried spironolactone at least once. Forty-four of 130 (33.8%) discontinued spironolactone due to side-effects after a mean of 11.1 months; 59/141 (41.8%) trials of spironolactone resulted in at least one side-effect; therapy was stopped in 30/141 (21.3%) trials due to raised potassium or creatinine. Significant risk factors for raised potassium/creatinine were age and baseline potassium level. CONCLUSIONS: Potentially serious side-effects are common despite appropriate use of spironolactone.

Age Factors↗
PubMed1978

Increased serum oestrone and oestradiol following spironolactone administration in hypertensive men.

The present study was undertaken to evaluate long-term effects of spironolactone on basal serum oestrone, oestradiol, testosterone, LH and prolactin concentrations in hypertensive male patients. Serum prolactin response to TRH was also evaluated. Patients were divided into two groups: a conventional-dosage group, consisting of six males with essential hypertension who took 75 to 150 mg of spironolactone daily for 12 weeks, and a high-dosage group, consisting of two males with idiopathic hyperaldosteronism who took 300 mg of spironolactone daily for more than 40 weeks. In the conventional-dosage group, serum oestrone concentrations significantly increased (P less than 0.01) at 12 weeks, serum oestradiol concentrations gradually increased throughout the study period, however, the increments were not statistically significant (P less than 0.2). Basal serum testosterone, LH and prolactin concentrations were not significantly changed throughout the study period. Enhancement of serum prolactin response to TRH was not found in any of the patients in the conventional-dosage group. In the high-dosage group, serum oestrone maintained high levels from the beginning of this study, and serum oestradiol concentrations increased with the development of gynaecomastia. Serum testosterone, LH and prolactin concentrations did not show any definite change throughout the study period. Thus, long-term spironolactone treatment increased the serum levels of oestrone and oestradiol in hypertensive men followed by the development of gynaecomastia. The elevation in circulating oestrogens could well explain the oestrogenic side-effects of spironolactone treatment.

Adult↗
PubMed1980

Long term spironolactone and the adrenal cortex in essential hypertension.

In view of recent evidence that spironolactone may inhibit synthesis of corticosteroids by a direct effect on the adrenal cortex, adrenocortical function was studied in eight patients with essential hypertension who had been treated with spironolactone from 3 months to 14 years. Their 24 h renal excretion of adrenocorticoid metabolites and the responses of cortisol, aldosterone and 18-hydroxy-11 -deoxycorticosterone (18-OH-DOC) to an incremental infusion of tetracosactrin (1-24 ACTH) were compared with those in eight patients with recently diagnosed essential hypertension who had received no spironolactone. The spironolactone-treated group had a significantly higher excretion of aldosterone, whilst the excretion of other adrenocorticoid metabolites did not differ. The same group also required less tetracosactrin to stimulate a detectable rise of plasma cortisol and 18-OH-DOC, they had greater plasma 18-OH-DOC responses at all infusion rates and, at the lowest infusion rates, had greater aldosterone responses. These results indicate that long-term spironolactone therapy does not inhibit adrenocortical function and may have some stimulatory effects.

18-Hydroxydesoxycorticosterone↗
PubMedDate not supplied

Racial differences in potassium response to spironolactone in heart failure.

Evidence of racial differences in aldosterone concentrations and K+ disposition suggests that response to aldosterone antagonism might vary by race. The authors sought to determine whether K+ response to spironolactone differs between African Americans and Caucasians with heart failure. Heart failure patients of African-American (n = 34) or Caucasian (n = 17) race were started on spironolactone 12.5 mg/d, with up-titration as tolerated. Laboratory values and drug therapy were similar between racial groups at baseline. Spironolactone was titrated to a median dose of 25 mg/d in both groups. Neither concomitant medications nor serum creatinine changed significantly in either group during spironolactone dose titration. Median serum K+ concentrations increased by 0.5 mEq/L (range, -0.7 to 1.6 mEq/L) in Caucasians, but only 0.1 mEq/L (range, -0.8 to 0.9 mEq/L) in African Americans; p < 0.01. These data suggest that African Americans with heart failure may be less responsive to the renal effects of spironolactone.

Adult↗
PubMed1976

Renin concentrations and effects of propranolol and spironolactone in patients with hypertension.

In a crossover study 32 patients with hypertension were randomly allocated to treatment with spironolactone 200 mg/day for two months, propranolol 320 mg/day for two months, and a combination of both drugs at half the dose. Between the treatments placebo was given for two months. Both spironolactone and propranolol lowered the blood pressure significantly in both positions. The initial plasma renin activity (PRA) levels ranged from 0-4 to 5-0 mug angiotensin I l-1 h-1, and there was a close correlation between these levels and the effects of the drugs: with increasing PRA the response to propranolol was better while the opposite was true for spironolactone. Spironolactone reduced the blood pressure more at eight than at four weeks, while no such difference could be shown for propranolol. Spironolactone and propranolol together decreased the blood pressure still further irrespective of the initial PRA. All patients achieved a normal supine blood pressure.

Administration, Oral↗
PubMed2003

Working heart function in diabetes is not improved by spironolactone treatment.

Aldosterone antagonism has emerged as an important strategy for end-stage congestive heart failure. To evaluate the potential contribution of aldosterone towards the cardiac complications of diabetes, this study examined the effects of chronic aldosterone receptor blockade (with spironolactone) on isolated working heart function in streptozotocin (STZ) - induced diabetic rats. Wistar rats were divided into four groups: control, control spironolactone-treated, diabetic, and diabetic spironolactone-treated. Following chronic spironolactone treatment (8 weeks), cardiac function was assessed in terms of the rate of contraction (+dP/dT), rate of relaxation (-dP/dT), and left ventricular developed pressure (LVDP). Untreated diabetic rats exhibited marked cardiac dysfunction when compared with age matched controls (p < 0.001). Long-term spironolactone treatment did not improve these parameters. These data demonstrate the lack of beneficial effects of aldosterone receptor blockade on isolated working heart function in diabetes.

Animals↗
PubMed1981

Renal and systemic acid-base effects of chronic spironolactone administration.

Studies in dogs were carried out to investigate the effects of chronic administration of the mineralcorticoid antagonist spironolactone (15 mg/kg orally) on renal and systemic acid-base metabolism. In adrenalectomized dogs administered fixed mineralocorticoid and glucocorticoid replacement, spironolactone resulted in a definite renal antimineralocorticoid effect, as evidenced by natriuresis and chloruresis, and sustained metabolic acidosis and hyperkalemia due in part to impaired renal secretion of hydrogen and potassium. In adrenalectomized dogs receiving physiological glucocorticoid without mineralocorticoid, metabolic acidosis also occurred, but a marked stimulatory effect of spironolactone on net acid excretion occurred in association with increased urinary SO4-2 and total nitrogen excretion. Accordingly, spironolactone results in sustained renal tubular acidosis when administered in the presence of constant physiological levels of mineralocorticoid and glucocorticoid steroids. When administered under conditions of complete lack of mineralocorticoid activity, spironolactone exerts systemic and renal acid-base effects similar to those of a glucocorticoid steroid, namely, increased protein catabolism and sulfuric acid production with resultant extrarenal metabolic acidosis associated with increased net acid excretion.

Acid-Base Equilibrium↗
PubMed2000

CYP11B2 expression in rat liver and the effect of spironolactone on hepatic fibrogenesis.

OBJECTIVE: In consideration of the hypothetical possibility that locally produced aldosterone is likely to take an active part in fibrogenesis of the liver, we undertook the present study to investigate the expression of aldosterone synthase gene CYP11B2 in rat liver and the curative effect of spironolactone on fibrosis of the liver. METHODS AND MATERIALS: 160 Wistar rats weighing about 250 g were divided into four groups as follows: model group, spironolactone group, malotilate group and control group. After 2, 4, 6, 8 and 10 weeks, the animals were sacrificed. Morphological examination was based on microscopic and electron microscopic findings. The area of collagen was examined by an Image Analyse System (Leica). By means of reverse transcriptase-polymerase chain reaction and in situ hybridization, the expression of CYP11B2 was detected. RESULTS: The expression of CYP11B2 mRNA, which was localized in the endoplasm of fat-storing cells, was upregulated when fibrogenesis occurred. The grade of fibrosis and the area of collagen in the spironolactone group were less than those in the model group before the 6th week (p < 0.05). After the 6th week, there was no significant difference between the spironolactone group and the model group (p > 0.05). CONCLUSIONS: The expression of CYP11B2 mRNA is upregulated in fibrotic liver. Spironolactone can partly have a fibrogenesis-inhibiting effect in the early stage of CCl(4)-induced hepatic fibrogenesis.

Animals↗
PubMed2002

Effect of spironolactone on impaired fibrinolysis of hypertensive patients.

BACKGROUND/AIMS: Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have beneficial effects on impaired fibrinolytic activity of hypertensive patients. The aim of the study was to evaluate the effect of antialdosterone treatment on impaired fibrinolysis of hypertensive patients. METHODS: Fourteen hypertensive outpatients and 14 normotensive healthy volunteers participated in this study. Blood samples for plasminogen activator inhibitor-1 (PAI-1) antigen and tissue plasminogen activator (t-PA) antigen were obtained at baseline in all patients and control subjects. Then all hypertensive patients used spironolactone 50 mg/day for a week. Blood samples were again obtained after a week of spironolactone treatment. RESULTS: The mean basal plasma level of PAI-1 of hypertensive patients was higher than those of the normotensive control group (60.98 +/- 4.2 vs. 24.09 +/- 1.61 ng/ml, p < 0.01) The mean basal t-PA level was similar in the hypertensive and control subjects (7.49 +/- 0.65 vs. 8.78 +/- 0.92 ng/ml, p > 0.05). The mean PAI-1 level decreased after a week of spironolactone treatment (60.98 +/- 4.2 vs. 42.99 +/- 7.98 ng/ml, p < 0.05). The mean plasma t-PA level of hypertensive patients increased after spironolactone treatment (7.49 +/- 0.65 vs. 11.09 +/- 1.33 ng/ml, p < 0.05). CONCLUSION: This study shows that spironolactone improves impaired fibrinolysis in systemic hypertension. It provides evidence for a direct link between aldosterone and the fibrinolytic system in humans.

Adult↗
PubMed1982

Changes in intrarenal uric acid handling during chronic spironolactone treatment in patients with essential hypertension.

Intrarenal handling of uric acid was studied in 12 patients with essential hypertension under spironolactone treatment (200 mg/day). The degree of volume depletion during treatment was assessed from the changes in body weight and plasma renin activity (PRA). The results are compared with those in patients treated with chlorthalidone (50 mg/day). During spironolactone treatment, the serum uric acid level remained constant despite a progressive volume depletion which after 3 months reached levels identical to those achieved in the chlorthalidone-treated patients, whose serum uric acid level showed the expected rise (21%). The uric acid excretion during spironolactone treatment was markedly diminished (-28%), and thus the 24-hour clearance of uric acid was correspondingly decreased (-22%). It is concluded that spironolactone affects uric acid metabolism in two ways: it causes a decrease in uric acid renal clearance (probably mediated by the induced volume depletion and PRA elevation, as with other saluretics) and, probably, inhibits endogenous uric acid production to approximately the same degree as the clearance is decreased, so that no change in the serum uric acid level occurs. The purpose of the study was to investigate the effect of spironolactone on uric acid handling by the kidney. We found a decrease in uric acid clearance and uric acid excretion. Serum uric acid concentration did not change.

Body Weight↗
PubMed1997

Prevention of aortic fibrosis by spironolactone in spontaneously hypertensive rats.

We have previously shown that long-term angiotensin-converting enzyme (ACE) inhibition prevents the increase in aortic collagen in spontaneously hypertensive rats (SHRs), independent of blood pressure reduction. More recently, we reported that the effects of ACE inhibition in the prevention of aortic collagen accumulation were related to the inhibition of angiotensin II actions on angiotensin II type 1 receptors. Aldosterone, the synthesis of which is mainly modulated by angiotensin II through type 1 receptor stimulation, is known to promote cardiac fibrosis in different experimental models. The aim of the present study was to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in SHRs. For this purpose, we compared the effects of a 4-month treatment with the aldosterone antagonist spironolactone with the ACE inhibitor quinapril in 4-week-old SHRs. Control SHRs and Wistar-Kyoto (WKY) rats received placebo for the same period of time. At the end of treatment, in conscious SHRs vs WKY controls, quinapril completely prevented the development of hypertension, whereas spironolactone produced only a slight but significant reduction in blood pressure. Aortic hypertrophy was significantly prevented by ACE inhibition but not by spironolactone. On the contrary, aortic collagen accumulation was completely prevented by both quinapril and spironolactone. In the latter case, collagen density was significantly below that of WKY controls. These results show that in SHRs, spironolactone can markedly prevent aortic fibrosis in the presence of a very slight antihypertensive effect. It is suggested that ACE inhibition or type 1 receptor antagonist-induced prevention of aortic collagen accumulation is at least partially related to aldosterone inhibition.

Animals↗
PubMedDate not supplied

Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study.

In a prospective, double-blind, intraindividual, cross-over, placebo-controlled multicenter study, clinical and biochemical effects of once daily postprandial dose regimens of 50, 100, and 200 mg spironolactone were investigated in 45 outpatients with primary hypertension, WHO (World Health Organization) Stage I-II. Each of the three active therapy periods, which were randomly allocated to patients, were of 2 months' duration, with intervening placebo periods, Clinical and biochemical parameters, including furosemide-stimulated plasma renin activity (PRA), were recorded at regular intervals. All three spironolactone doses resulted in statistically significant blood pressure (BP) reductions independent of initial pretreatment levels and yielded satisfactory BP control in more than half of the patients. The 200 mg daily dose of spironolactone was found to be more effective than 50 but not 100 mg. When, correlating blood pressure response (delta MAP) to PRA, the profiling for positive spironolactone responders was characterized by high age and low PRA, irrespective of sex. Spironolactone therapy resulted in decreased serum sodium and magnesium values; potassium, creatinine, urate, and triglyceride levels were increased. However, all treatment values were within normal ranges. Side effects were infrequent and mainly of endocrine nature.

Administration, Oral↗
PubMed1987

Spironolactone-induced agranulocytosis.

Agranulocytosis associated with spironolactone administration is described in a 57-year-old man. Four days after initiation of spironolactone, leukocyte counts decreased from 8.2 to 2.3 X 10(9)/L with 6% neutrophils. Spironolactone, domperidone, and prochlorperazine were discontinued. Domperidone and prochlorperazine were reintroduced and there was concomitant improvement of the leukocyte and neutrophil counts. Substitution of triamterene for spironolactone was not associated with recurrent leukopenia. The potential association of spironolactone with granulocytopenia warrants increased awareness of this rare but serious adverse drug reaction.

Agranulocytosis↗