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PubMed1984

The effect of long-term treatment with spironolactone on sodium pump abnormalities in the red blood cells of patients with Bartter's syndrome.

To elucidate the possible sodium transport alterations across the cell membranes in Bartter's syndrome and their influencing by spironolactone treatment Na+-K+-ATPase activity was studied by means of radioactive 86Rubidium influx into red blood cells (RBC) of patients with Bartter's syndrome prior to and after a long-term spironolactone administration. As compared with the control subjects and patients with primary aldosteronism the patients with Bartter's syndrome had a more than 5 times higher 86Rb uptake by the RBC, especially in the ouabain-sensitive component. A long-term spironolactone treatment led to the decrease of this high influx. Serum of patients with Bartter's syndrome incubated with healthy RBC distinctly increased their 86Rb influx. The increase nevertheless did not reach the values in the RBC of untreated patients with Bartter's syndrome. Even if our results do not allow to explain fully the mechanism responsible for the Na+-K+-ATPase changes in the RBC of these patients, analysis of the studied parameters demonstrated that none of the known humoral factors as aldosterone, renin, prostaglandins, or changes of the serum potassium were responsible for these abnormalities. The changes of sodium transport in RBC of patients with Bartter's syndrome could be a part of a more general disturbance of the transport mechanism and could significantly participate in the pathogenesis of this disease.

Adult↗
PubMed1994

Spironolactone administration and training-induced hypervolemia.

The purpose of this study was to determine the contribution of aldosterone to plasma volume expansion accompanying short-term exercise training. Twelve healthy males (age = 26.5 +/- 5.8) cycled for 120 min on three consecutive days at a relative exercise intensity of 65% VO2max. Half of the subjects were treated with 25 mg of spironolactone taken four times daily to suppress the effects of aldosterone. Resting plasma volume increased significantly (501 +/- 83 ml, p < 0.05) from pretraining in control subjects, but not for drug-treated subjects (163 +/- 94 ml). Spironolactone attenuated gains in resting plasma volume, serum sodium content, and serum osmolal content by 67%, 79% and 66%, respectively. Spironolactone-treated and non-treated subjects experienced similar increases in total serum protein content sufficient to increase the plasma volume by approximately 290 ml. It was not determined why drug-treated subjects attained less of a plasma volume expansion than that expected by the increase in oncotic pressure. In conclusion, two-fifths of the plasma volume expansion induced by 3 d of endurance cycling could be attributed to aldosterone activity, and the remaining three-fifths could be explained by the expansion of intravascular protein mass. Other neurohormonal influences may have contributed to the overall plasma volume expansion but this experiment did not allow for their exclusion.

Adolescent↗
PubMed1985

[Spironolactone in the treatment of portal hypertension in liver cirrhosis. A new therapeutic principle?].

Five patients with liver cirrhosis, portal hypertension and oesophageal varices received spironolactone in daily doses of 50-200 mg. Measurements of hepatic vein occlusion pressure at intervals of 1 to 5 months showed a pressure reduction of between 9 and 11 mm Hg. Thus the pressure lowering effect of spironolactone is about the same as that of beta-blockers. Since spironolactone is without the well known side effects of beta-blockers this therapeutic approach has wide application in the long term drug therapy of portal hypertension.

Blood Pressure Determination↗
PubMed1996

Stability of ketoconazole, metolazone, metronidazole, procainamide hydrochloride, and spironolactone in extemporaneously compounded oral liquids.

The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Ketoconazole 20 mg/mL, metolazone 1 mg/mL, metronidazole 50 mg/mL, procainamide hydrochloride 50 mg/ mL, and spironolactone 25 mg/mL were prepared in a 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories), and cherry syrup and placed in 120-mL polyethylene terephthalate bottles. The sources of the drugs were powder, capsules, and tablets. Six bottles were prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the dark. A sample was removed from each bottle immediately after preparation and at intervals up to 60 days and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. At least 93% of the initial drug concentration was retained in all the oral liquids for up to 60 days. There were no substantial changes in the appearance or odor of the liquids, or in the pH. Ketoconazole 20 mg/mL, metolazone 1 mg/mL, metronidazole 50 mg/mL, procainamide hydrochloride 50 mg/ mL, and spironolactone 25 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three extemporaneously compounded oral liquids. INDEX TERMS: Anti-infective agents; Antifungals; Capsules; Cardiac drugs; Cherry syrup; Compounding; Containers; Diuretics; Incompatibilities; Ketoconazole; Liquids; Metolazone; Metronidazole; Polyethylene terephthalate; Powders; Procainamide hydrochloride; Spironolactone; Stability; Storage; Suspending agents; Tablets; Temperature; Vehicles.

Administration, Oral↗
PubMed1979

Opposing effects of deoxycorticosterone and spironolactone on isoprenaline-induced myocardial infarction.

Adult, male Sprague-Dawley rats were subjected to massive myocardial infarction with isoprenaline. Some of the animals were treated with the potent mineralocorticoid, deoxycorticosterone, or the anti-mineralocorticoid, spironolactone. Autopsies spaced at sequential time intervals demonstrated that circulating levels of enzymes, eg, CPK, SGOT, SGPT and LDH, lipids, eg, triglycerides, free fatty acids, and cholesterol, glucose, Bun, and corticosterone rose in conjunction with on-going necrosis and became lowered in conjunction with myocardial repair. Body and organ weights, ie, adrenal, thymus, heart, and kidney, underwent dynamic changes commensurate with necrosis and repair. Animals given isoprenaline alone died (52% survival) during the height of their massive infarct and congestive heart failure (Days 3 and 4). Animals treated with DOC showed the most severe congestion but died (36% survival) during the late repair phase (Days 7 and 8). Animals treated with spironoloactone showed the most effective clearance of thoracic fluid and also dies (18% survival) during the late repair phase (Days 7 and 8). These spironolactone-treated animals had large, left ventricular aneurysms with organised, adherent thrombi. It is believed that alterations in electrolyte balance induced by DOC or spironolactone caused changes in adrenocortical function which greatly modified the usual pathophysiological response to myocardial infarction.

Animals↗
PubMed1982

Effects of spironolactone (aldosterone antagonist) on electrolyte and water content of the cauda epididymidis and fertility of male rats.

It has previously been shown that the rat cauda epididymidis actively reabsorbs Na+ in exchange with K+. This coupled Na+/K+ transport is stimulated by aldosterone. These transport processes create a low Na+ and high K+ environment which appears to be (in part) responsible for sperm quiescence during storage. The effects of aldosterone antagonist, spironolactone, on the electrolyte and water content of the cauda epididymidis, sperm motility initiation and fertility of male rats were investigated in the present study. It was found that treatment of rats with spironolactone (10 mg/kg per day for 4 to 17 days) led to a significant fall in K+ (18%) and sperm (21.5%) concentrations in the cauda epididymal fluid. However, the Na+ concentration remained unchanged. The fall in sperm concentration may be taken to indicate an increase in fluid volume which is secondary to an inhibition of water absorption. When corrected for an increase in volume, there was no change in the amount of K+ in the fluid but the amount of intraluminal Na+ was increased. Despite a fall in K+ and sperm concentration, the capacity of the cauda sperm to initiate motility and fertility of the animals were apparently not affected by spironolactone treatment. It is concluded that the fertility capacity of spermatozoa is rather resistant to drugs which interfere with electrolyte and water transport across the caudal epididymal epithelium.

Animals↗
PubMed2002

Life-threatening hyperkalemia: a complication of spironolactone for heart failure in a patient with renal insufficiency.

IMPLICATIONS: Serum potassium concentration should be measured immediately before operation to detect hyperkalemia in heart failure patients treated with spironolactone. Renal insufficiency, advanced age, potassium supplementation, decompensated congestive heart failure, and a spironolactone dose larger than 25 mg/d increase the risk of hyperkalemia as a consequence of spironolactone therapy.

Aged↗
PubMed1996

Increase in the basal tone of guinea pig thoracic aorta induced by ouabain is inhibited by spironolactone canrenone and potassium canrenoate.

Guinea pig aorta rings repeatedly stimulated with phenylephrine (1 microM) in the presence of Krebs solution containing ouabain (0.8 microM) or low K+ (0.5 mM) concentration produced an increase in basal tone. This effect is due to an increase in intracellular Ca2+ as a consequence of Na(+)-K+ATPase pump inhibition induced by receptorial (ouabain) or ion imbalance (low K+) mechanism. We investigated the effect of spironolactone and its metabolites canrenone and potassium canrenoate on the increase in basal tone of guinea pig aorta rings. Spironolactone, canrenone, and potassium canrenoate, in a concentration-dependent manner (3-30 microM), inhibited the increase in basal tone induced by ouabain, most likely acting as antagonist for ouabain binding site on Na(+)-K+ATPase pump. Indeed, this effect appears to be a feature of these drugs since structurally related drugs, such as aldosterone and hydrocortisone, were ineffective. Conversely, all the drugs tested reduced, to a certain degree, the increase in basal tone produced by low K+ Krebs solution, implying that this could be a non-specific effect. Our results may indicate that spironolactone, canrenone, and potassium canrenoate act in hypertension by interfering with mechanisms in which an ouabain-like factor is involved.

Animals↗
PubMed1987

Spironolactone and estrogen-progestin therapy for hirsutism.

Sixteen women with hirsutism used spironolactone, 100 mg daily without interruption, plus norethindrone (1 mg) and ethinyl estradiol (35 mg) for 21 of each 28 days. Clinical improvement occurred in 11 of the 16 patients and also in an additional patient when the dose of spironolactone was increased to 200 mg daily. Spironolactone 100 mg daily plus norethindrone and ethinyl estradiol resulted in significant reduction in serum total testosterone, serum free testosterone, and percentage of free testosterone. Side effects were infrequent.

Drug Administration Schedule↗
PubMed1989

Reassessment of cross-reactivity of spironolactone metabolites with four digoxin immunoassays.

Spironolactone and one of its metabolites, canrenone, cross-react with some digoxin immunoassays to result in erroneous serum digoxin concentrations. Recently, additional compounds, 7-alpha-thiomethylspirolactone (7-a-TMS) and 6-beta-hydroxy-7-alpha-thiomethylspirolactone (6-B-OH-7-a-TMS), have been reported to be quantitatively important metabolites of spironolactone. This study was initiated to evaluate the cross-reactivity of these metabolites, canrenone, and spironolactone with four different digoxin immunoassays. Blank serum was spiked with each compound to yield concentrations reported to occur in vivo. Samples were analyzed in duplicate by each of the following immunoassays: fluorescence polarization immunoassay (FPIA); affinity-column-mediated immunoassay (ACMIA); radioimmunoassay (RIA); and enzyme immunoassay (EIA). The 7-a-TMS metabolite cross-reacted with both the RIA and ACMIA methods. Apparent digoxin concentrations were as great as 0.39 ng/ml for this metabolite at the highest concentration evaluated, 600 ng/ml. At the lowest concentrations evaluated with the 7-a-TMS metabolite, 50 ng/ml, apparent digoxin concentrations as high as 0.28 ng/ml were reported. The 6-B-OH-7-a-TMS metabolite did not cross-react to a significant extent with any of immunoassays studied. Canrenone cross-reacted with the ACMIA method at a concentration of 100 ng/ml. The EIA method exhibited no apparent cross-reactivity with any of the compounds, whereas the FPIA method exhibited minimal cross-reactivity. The results of this study indicate that the 7-a-TMS metabolite cross-reacts to a significant extent with some immunoassays; however, this is not true for the 6-B-OH-7-a-TMS metabolite.

Adult↗
PubMed1975

The effect of spironolactone (Aldactone) and methyldopa in low and normal renin hypertension.

The effect on BP of 100 and 200 mg spironolactone/day has been compared with that of methyl-dopa, 750 mg/day, and with combined treatment with both drugs in 32 patients with essential hypertension. The 28 patients who completed the entire investigation were treated for 30 weeks, divided into 4 treatment periods and 4 placebo periods of equal duration. BP did not fall significantly during the initial placebo period, and at the end of each of the intervening placebo periods it rose to pretreatment levels. A signifcant decrease in mean BP was found during the 4 treatment periods. A fall exceeding 14% was registered in 32% of the patients after methyldopa, 750 mg/day, in 50% of the patients after spironolactone, 200 mg/day, in 89% after combined treatment with both drugs, and in 29% after spironolactone, 100 mg/day. Low renin hypertension was found in 9 of the 28 patients. The average decrease in mean BP after sironolactone, 200 mg/day, methyldopa, 750 mg/day, and after combined treatment did not differ significantly between the low and the normal renin group. The rationale for using diuretics such as spironolactone or thiazide as the basic therapy in essential hypertension is discussed. It is concluded that both are useful in the treatment of essential hypertension and might be used alone or in combination.

Adult↗
PubMed1977

The effects of four months' treatment with spironolactone on systemic blood pressure, cardiac output and plasma renin activity in hypertensive patients.

The effect of spironolactone on BP, cardiac output, plasma renin activity and urinary excretion of electrolytes has been studied in 12 hypertensive patients. After 1 month of spironolactone therapy there was a significant decrease in arterial BP. Urinary sodium excretion was significantly decreased and plasma renin activity increased. After four months of spironolactone therapy there was no further decrease in arterial BP. Cardiac output, heart rate and stroke volume were unchanged in the supine position, but the calculated total peripheral vascular resistance (TPVR) was reduced, indicating that the lower BP was mainly a result of dilatation of the resistance vessels. During exercise there was still a significant decrease in arterial BP but this was related to a decrease in both cardiac output and TPVR.

Adult↗
PubMed1983

The effect of spironolactone on lipid, glucose and uric acid levels in blood during long-term administration to hypertensives.

Spironolactone, an aldosterone antagonist, was given in a daily dose of 100 mg to 15 patients with primary hypertension for one year. Fasting levels of lipids, uric acid, glucose, insulin, potassium and growth hormone were measured before and after 6 and 12 months of treatment. Total cholesterol, LDL cholesterol, glucose, potassium and growth hormone were unchanged, HDL cholesterol fell from (mean +/- SD) 1.5 +/- 0.6 to 1.1 +/- 0.3 mmol/l (p less than 0.05) after 6 months of treatment and remained lowered (1.0 +/- 0.3 mmol/l) (p less than 0.01) after 12 months of treatment. There was a transient fall after 6 months of treatment in triglycerides from 2.4 +/- 1.5 to 2.0 +/- 1.1 mmol/l (p less than 0.05), uric acid from 380 +/- 73 to 342 +/- 58 mumol/l (p less than 0.05) and an increase in insulin from 16 +/- 9.5 to 28.6 +/- 26.8 mU/l (p less than 0.05). The blood glucose curves above fasting levels after glucose loading were unchanged during spironolactone treatment, whereas the area under the net insulin curve was higher after 6 months of treatment (163 +/- 103 mU X h/l) than before treatment (105 +/- 71 mU X h/l), indicating a small and transient insulin resistance. Thus, spironolactone impaired the glucose tolerance transiently and gave small and almost transient changes in fasting serum lipid and uric acid levels.

Adult↗
PubMed1992

Oral spironolactone therapy in male patients with rosacea.

Spironolactone at 50 mg/day was orally administered for four weeks to 13 male patients with rosacea in order to observe its clinical effectiveness. Serum estradiol (E2), 17OH-progesterone (17OH-P4), testosterone (T), androstenedione (delta 4 A), dihydrotestosterone (DHT), dehydro-epiandrosterone sulfate (DHEA-S) were measured prior to and after treatment. Although there were no significant changes in T, delta 4A, DHT, or DHEA-S, the serum levels of 17OH-P4 increased significantly. E2 tended to increase, although the change was not significant. Two of the 13 patients discontinued spironolactone treatment because of general malaise, but seven of the remaining eleven patients exhibited an improvement in their rosacea. These findings demonstrate that a low dose of spironolactone is effective in the treatment of rosacea in some male patients and suggest that it is possible that changes in the metabolism of sex steroid hormones such as cytochrome p-450 isozymes have some bearing on the etiology of rosacea.

Administration, Oral↗
PubMed1996

Topical spironolactone reduces sebum secretion rates in young adults.

The effects of topically applied spironolactone on the sebum secretion rates (SSR) of young adults were investigated. SSR was expressed as the ratio of wax esters/[cholesterol+cholesterol esters] (WE/[C+CE]) and the amount of sebaceous lipids (squalene, triacylglycerol and wax esters). Topical spironolactone 5% gel applied to the right cheeks of the subjects produced a significant reduction in the SSR at 12 weeks (4 weeks after termination of application), but not at 8 weeks (the end of treatment). Untreated "control" areas (the left cheeks of the subjects) showed no significant change during the study. None of the subjects experienced skin rash or signs of local irritation. This results suggests that topical spironolactone may be effective in the treatment of acne patients with high SSR.

Administration, Topical↗
PubMed1976

The pharmacodynamics of single doses of prorenoate potasssium and spironolactone in fludrocortisone treated normal subjects.

1 The pharmacodynamic profile of single oral doses of prorenoate potassium (40 mg) and spironolactone (100 mg), as judged by reversal of the effects of fludrocostisone on the urinary electrolyte composition, was compared to that of placebo in a double-blind crossover study in six healthy subjects. 2 Both drugs showed evidence of significant activity in all periods between 2-16 h after treatment, and the time course of their activity was very similar. 3 In the total 24 h period after treatment both drugs significantly increased sodium excretion, the Na/K ratio and the log 10 Na/K ratio over placebo values, and urine potassium concentration was significantly reduced. Changes in urine volume and in potassium excretion were not significant. 4 The responses to prorenoate potassium (40 mg) were not significantly different from those to spironolactone 100 mg), and were very similar as judged by the urine log 10 Na/K ratio, indicating that the two drugs were approximately equiactive at these doses. 5 Reductions in urinary potassium excretion, when expressed in relation to the amount of sodium excreted, were significantly larger after prorenoate potassium than after spironolactone, confirming a qualitative difference in the pharmacological activity of the two drugs which has been reported previously.

Administration, Oral↗
PubMed1984

Oral spironolactone improves acne vulgaris and reduces sebum excretion.

In a consecutive series of thirty-six male and female patients referred with severe acne, the effect of 3 months' treatment with placebo or spironolactone (50-200 mg daily) on sebum excretion and clinical and endocrine status was evaluated double-blind. Twenty-six patients completed the study. Abnormal free androgen indices were found in 27% of the original nineteen female subjects. Spironolactone reduced sebum excretion in all female subjects, but there was no correlation between sebum response and androgen status. The clinical response was dose-dependent, with maximum subjective and objective benefit when spironolactone doses of 150-200 mg were used.

Acne Vulgaris↗
PubMed1986

Oral spironolactone: an effective treatment for acne vulgaris in women.

The effect of oral spironolactone (200 mg daily) on acne vulgaris has been studied in 21 women in a randomized, placebo-controlled, double-blind crossover study using 3 month treatment periods. Compared with placebo, spironolactone produced significant improvement as assessed by subjective benefit (P less than 0. 001), number of inflamed lesions (P less than 0 . 001) and by an independently evaluated photographic method (P less than 0 .02). There was a fall in sex hormone binding globulin but no significant changes in plasma testosterone and derived free testosterone. Initial plasma androgen levels were no higher in responders than in non-responders, nor did oral contraceptive use appear to affect clinical response. Spironolactone is a useful alternative therapy for women with acne vulgaris.

Acne Vulgaris↗