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PubMed1978

Effectiveness of high-dose spironolactone therapy in patients with chronic liver disease and relatively refractory ascites.

Ten patients with ascites due to chronic liver disease were treated with spironolactone as the sole diuretic in doses of 300 to 600 mg daily. Prior to spironolactone treatment ascites was relatively refractory as indicated by baseline 24-hr urine sodium values of less than 5 mEq and natriuresis of less than 30 mEq following 200 mg hydrochlorothiazide. With spironolactone, mean daily weight loss was 540 g and natriuresis 74 mEq; diuresis was considered satisfactory in nine of ten patients. Untoward effects were limited to a single episode of hepatic encephalopathy, a small fall in serum magnesium in several patients, and three instances of hyperkalemia (5.5, 5.6, and 7.5 mEq/liter). In spite of the tendency to hyperkalemia, urinary potassium excretion increased in seven of the ten patients. There was no rise in serum urea nitrogen or creatinine. Hydrogen ion excretion decreased initially leading to mild hyperchloremic acidosis. Serum urate did not increase.

Adult↗
PubMed1975

Control of plasma aldosterone in a patient with Conn's syndrome before and during spironolactone medication.

In a patient suffering from Conn's syndrome analysis of short-time fluctuations of plasma aldosterone, plasma cortisol and plasma renin activity were performed before and after a 9-months therapy period with spironolactone. Under the former conditions aldosterone was secreted episodically and a highly significant correlation was found between plasma aldosterone and plasma cortisol (r=0.817, p is less than 0.001) while plasma renin activity was undetectable (is less than 0.16 ng/ml/3hr). Following a 9-month therapy with spironolactone episodic secretion of aldosterone and the significant correlation between aldosterone and cortisol persisted (r=0.819, p less than 0.001) in the presence of an abnormally high plasma renin activity. First when the secretion of ACTH was suppressed by dexamethasone a weak correlation was found between renin activity and aldosterone (r=0.517, p is less than 0.05). Our results show that both before and after a 9-months therapy with spironolactone episodic aldosterone release of an aldosterone producing adrenal adenoma was mediated through ACTH and that endogeneous angiotensin II had no or only little influence.

Adenoma↗
PubMed1978

Non-interaction of spironolactone medication and cortisol metabolism in man.

In 5 healthy subjects and in 5 patients with decompensated liver diseases, the concentrations of cortisol, canrenone and canrenoate-K were determined after single doses and after a long-term treatment with spironolactone. The concentrations of the metabolites of spironolactone were determined fluorimetrically, those of cortisol by a highly specific radioimmunoassay with previous chromatographic separation. As a result, non-interaction between spironolactone medication and cortisol metabolism, even at high dose and long-term treatment conditions, was established neither in normal test subjects nor in patients with liver failure.

Canrenoic Acid↗
PubMed1989

Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism.

The clinical and hormonal response to 12-month therapy with the antiandrogen, spironolactone, in conjunction with near-physiologic doses of female gonadal steroids in 50 transsexual males, is presented. An unselected referred series of 61 men with the psychiatric diagnosis of transsexualism was treated; 10 subjects who had received previous gonadal surgery and 1 man with Klinefelter's syndrome were excluded. Twenty-seven conventionally treated (CT; high-dose estrogen), age 34.4 +/- 10.5 years, mean +/- SD, and 23 untreated patients (SPS), age 30.7 +/- 6.2 years, were studied. Following the initial visit, all 50 were begun on spironolactone and low-dose female hormone therapy. Despite high-dose estrogen treatment for more than 2 years, the mean testosterone (T) level for the CT group was not in the female range (169 +/- 193 ng/dl; normal 20-80). Spironolactone, in doses of 200-600 mg/day, lowered T to the female range in both groups after 12 months (CT 87 +/- 111 and SPS 49 +/- 41 ng/dl). This was achieved in the CT group despite decreases in estrogen dose and discontinuation of parenteral therapy. SPS subjects experienced significant decreases in plasma T (642 +/- 236 to 49 +/- 41 ng/dl, p less than 0.001). Systolic blood pressure dropped (128 +/- 14 to 121 +/- 14 mm Hg, p less than 0.05). The clinical response, including decreased male pattern hair, breast development, feminization, and lack of erections was excellent in most subjects.

Adult↗
PubMed1981

[On the pharmacokinetics of spironolactone in the elderly].

The pharmacokinetics of canrenone were compared in 10 elderly (77.2 years) patients and 10 young (20.1 years) female persons after multiple oral dosing of 100 mg Spironolactone during steady-state. The concentrations were determined using both a specific HPLC-assay and a nonspecific fluorometric assay. Maximum as well as mean concentrations of canrenone in serum of the elderly subjects were approximately twice as high as those in the young. This was the consequence of an impaired capacity for elimination of spironolactone in the elderly subject. In addition the ratio of the other fluorigenic metabolites and of canrenone were higher in the elderly. Thus also shifts in the metabolic pathways of spironolactone occur with progressing age.

Aged↗
PubMed1977

Interaction between aldosterone and renomedullary prostaglandins. Competitive action between aspirin and spironolactone.

Aldosterone injected i.m. decreased the release of renomedullary PGEs and the index (urinary Na/K ratio) in conscious normotensive intact and adrenalectomized rats. Coadministration of spironolactone increased the release of PGEs as well as the index (urinary Na/K ratio). The effect of spironolactone was partly inhibited by aspirin injected in a ratio 5:1 (aspirin:spironolactone), and effect which could be reversed by the infusion of a synthetic prostaglandin (PGA2) in a subhypotensive dose.

Adrenalectomy↗
PubMed1995

The effects of spironolactone on testosterone fractions and sex-hormone binding globulin binding capacity in hirsute women.

This study explored the effect of the anti-androgen spironolactone on sex-hormone binding globulin (SHBG) and the distribution of circulating testosterone (T) into various free and bound fractions in seven women with hirsutism assessed before and then monthly for three months on a regimen of spironolactone, 100 mg bid as the sole therapeutic agent. Blood samples were taken at each assessment time for a battery of androgen parameters and serum T fractions studies. None of the women were judged obese based upon body mass index values. After three months of spironolactone therapy, there was little change in the hirsutism index, and measurement of serum T, androstenedione, DHEA-S and 17 beta-estradiol showed no significant changes, the same occurring with SHBG-binding capacity. However, there was a shift in the distribution of circulating T, with a decrease in SHBG-bound T and an increase in albumin-bound and free T (non-SHBG-bound fractions). As previous reports suggest that non-SHBG-bound fractions represent bioavailable fractions, the current data suggests that T fraction studies may not be clinically useful parameters of hyperandrogenism in women receiving antiandrogen therapy.

Adolescent↗
PubMed1983

Antiandrogenic properties of spironolactone. Clinical trial in the management of female hirsutism.

The effect of spironolactone on female hirsutism was studied in 18 patients. The drug was administered at the dose of 400 mg for the first ten days and 300-200 mg later on in a first group of women (Group A); a second group (Group B) was given 200 mg spironolactone for the whole length of therapy. A significant decrease of the index of Ferriman and Gallwey (p = 0.01) was noted from the 100th day of treatment; acne and seborrhoea improved concomitantly. Plasma total testosterone values fell from 0.64 +/- 0.24 ng/ml to 0.32 +/- 0.12 ng/ml (p = 0.002) during the first 5 days only in the patients of Group A; in the other patients no significant changes were observed. PRL did not significantly change from pretreatment values; FSH and LH values at the 5th, 10th, and 15th day of therapy did not show a uniform course in both groups. On the basis of these results spironolactone administration appears promising in the therapy of female hirsutism.

Adult↗
PubMed2005

Effects of spironolactone and RU486 on gene expression and cell proliferation after freshwater transfer in the euryhaline killifish.

We have explored the possible mechanisms by which mineralocorticoid (MR) and glucocorticoid (GR) receptors regulate the response to freshwater transfer in the gills of the euryhaline killifish Fundulus heteroclitus. Killifish were implanted with RU486 (GR antagonist) or spironolactone (MR antagonist) at doses of 0.1-1.0 mg g(-1), and subsequently transferred from 10 per thousand brackish water to freshwater. Compared to brackish water sham fish, mRNA expression of CFTR and NKCC1 decreased in the gills of sham fish transferred to freshwater, whereas Na(+), K(+)-ATPase alpha(1a) mRNA expression and alpha protein abundance, as well as cell proliferation (detected using BrdU) increased. Spironolactone inhibited the normal increase in cell proliferation and Na(+), K(+)-ATPase expression after freshwater transfer. RU486 increased plasma cortisol levels and may have slightly inhibited Na(+), K(+)-ATPase activity, but did not change alpha(1a ) expression. RU486 had no effect on cell proliferation in the non-lamellar region of the gills, but increased proliferation in the lamellar region. Neither antagonist inhibited the suppression of CFTR or NKCC1 expression after freshwater transfer. Glucocorticoid receptor expression was reduced in all sham and antagonist treatments compared to untreated controls, but no other consistent differences were observed. The effects of spironolactone suggest that MR is important for regulating ion transport in killifish gills after freshwater transfer.

Adaptation, Physiological↗
PubMed1990

Peripheral action of spironolactone: plethysmographic studies.

The relation between vasodilation and the blood pressure-reducing action of spironolactone was studied in a randomized, placebo-controlled, double-blind, crossover study using 9 patients with essential hypertension. Vasodilation was studied by measuring blood flow in finger and calf (representative of skin and muscle circulation) by an electrocardiographic-triggered venous-occlusion plethysmograph. Treatment with spironolactone (100 mg twice daily for 4 weeks) produced significant decreases in systolic and diastolic blood pressure without significantly affecting heart rate. Blood flow through finger and calf increased, sometimes markedly, in 6 of the 9 patients, while vascular resistance decreased. This study confirms that the antihypertensive action of spironolactone is associated with vasodilation in many patients.

Blood Flow Velocity↗
PubMed1990

Spironolactone in the management of congestive heart failure.

Although many new drugs useful in the treatment of congestive heart failure have been introduced during the past 25 years, spironolactone continues to have an important role in the management of this condition. Spironolactone adds to the activity of the thiazide and loop diuretics to enhance the elimination of sodium and water. Furthermore, unwanted electrolyte disturbances such as hypokalemia and hypomagnesemia, associated with the administration of other classes of diuretics, can be minimized with spironolactone.

Diuretics↗
PubMed1991

Premenstrual tension: a placebo-controlled efficacy study with spironolactone and medroxyprogesterone acetate.

Forty-three healthy women with a characteristic history of premenstrual tension participated in a placebo controlled, crossover study. The effects of spironolactone (Aldactone) and medroxyprogesterone acetate (Gestapuran) on ten symptoms of premenstrual tension were evaluated. Placebo tablets as well as spironolactone and medroxyprogesterone acetate significantly improved a mood index score (which is a generally accepted method to measure premenstrual symptoms). Spironolactone and medroxyprogesterone acetate were however both significantly (P less than 0.05) better than placebo in relieving the symptoms.

Adult↗
PubMed1991

Spironolactone causes a rapid down regulation of sigma recognition sites in guinea pig brain and liver.

The effect of dosing guinea pigs with spironolactone (100 mg/kg twice daily for 3 days) upon the sigma recognition site labelled with [3H]-DTG was investigated. Animals were dosed with 100 mg/kg spironolactone twice a day for 3 days. Spironolactone treatment caused a decrease in sigma radioligand binding in membranes prepared from liver and brain but not in adrenals or testes. Saturation analysis of [3H]-DTG radioligand binding in the brain indicated that the decrease in specifically bound [3H]-DTG binding was due to a reduction in receptor number with no change in affinity. This method for the selective depletion of brain and liver sigma recognition sites will provide a useful tool for exploring the functional significance of this site.

Adrenal Glands↗
PubMed1976

Isolation and identification of a sulfur-containing metabolite of spironolactone from human urine.

In the urine of normal subjects who were given an oral dose of 500 mg spironolactone (3-(3-oxo-7alpha-acetylthio-17beta-hydroxy-4-androsten-17alpha-yl)-propionic acid gamma-lactone; Aldactone) together with 100uCi H-20, 21 spironolactone, a so far unknown major metabolite has been detected by thin layer chromatography. The metabolite then could be isolated by means of counter-current-distribution. According to masspectral and magnetic resonance data, the metabolite has been assigned the structure of 3-(3-oxo-7alpha-methyl sulfonyl-6beta, 17beta-dihydroxy-4-androsten-17alpha-yl)-propionic acid gamma-lactone. By oxidation of the corresponding methylsulfinyl compound - another already known metabolite of spironolactone - with m-chloroperbenzoic acid, a compound has been isolated which proved to be identical with the new metabolite according to TLC, MS and NMR.

Countercurrent Distribution↗
PubMed1992

Efficacy of low-dose captopril in addition to furosemide and spironolactone in patients with decompensated liver disease during blunted diuresis.

The renin-angiotensin-aldosterone system is activated by diuretics and involved in the diuretic resistance of cirrhotic patients with ascites and oedema. In previous studies relatively high doses of captopril (25-400 mg daily) were unsuccessful in promoting diuresis and natriuresis in these patients. We analyzed the efficacy of a low dose of captopril in eight patients with massive ascites resistant to therapy of salt/fluid restriction and increasing doses of spironolactone and furosemide. Mean duration of diuretic use was 73 days (range 7-240 days). After at least 3 days of observation on 80 mg furosemide and 100 mg spironolactone only, captopril was added. Four out of eight patients responded with an increase in natriuresis and diuresis; daily dose of captopril was 20.6 mg in responders and 26.5 mg in non-responders. After the addition of captopril the mean weight change was -7.5 kg in responders and +0.25 kg in non-responders. Mean urinary sodium output in responders increased from 72.8 (S.D. = 35.2) to 128.5 (63.5) mmol within 10 days. Increased diuresis in responders made diuretic reduction necessary: mean furosemide from 80 to 53.3 mg, and mean spironolactone from 100 to 68.1 mg. Creatinine clearances remained stable. High levels of plasma renin activity, plasma aldosterone and angiotensin-II were found in all patients. Non-responders showed more severe hyponatremia and higher vasopressin levels. Natriuretic atrial factor (NAF) was in the upper-normal range or slightly elevated in both groups. In non-responders we noticed low levels of cGMP in 24-h urine, compared with responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

High-performance liquid chromatographic determination of spironolactone and its metabolites in human biological fluids after solid-phase extraction.

A simple and sensitive high-performance liquid chromatographic procedure to determine spironolactone and its three major metabolites in biological specimens is described. The assay involves sequential extraction on C18 and CN solid phases, and subsequent separation on a reversed-phase column. In plasma samples, spironolactone and its metabolites were completely separated within 8 min using an isocratic mobile phase, while in urine samples a methanol gradient was necessary to achieve a good separation within 14 min. Recoveries for all analytes were greater than 80% in plasma and 72% in urine. Linear responses were observed for all compounds in the range 6.25-400 ng/ml for plasma and 31.25-2000 ng/ml for urine. The plasma and urine methods were precise (coefficient of variation from 0.8 to 12.5%) and accurate (-12.1% to 7.4% of the nominal values) for all compounds. The assay proved to be suitable for the pharmacokinetic study of spironolactone in healthy human subjects.

Chromatography, High Pressure Liquid↗
PubMed1995

Alterations of calcium metabolism and of parathyroid function in primary aldosteronism, and their reversal by spironolactone or by surgical removal of aldosterone-producing adenomas.

In order to investigate the possible existence of abnormal calcium metabolism and parathyroid function in primary aldosteronism (PA), we have compared the calcium/parathyroid hormone (PTH) profile of patients with PA with the profile of healthy normotensive subjects and of patients with essential hypertension (EH). Furthermore, we have evaluated the effects of spironolactone and the surgical removal of aldosterone-producing adenomas on the calcium/PTH profile in the PA patients. Four groups of 10 subjects each participated in the study: 1) hypertensive patients with PA, 2) patients with low-renin EH (LREH), 3) patients with normal-renin EH (NREH), 4) normotensive healthy subjects (NS). The four groups were well-matched for age, sex, body mass index, and renal function. The three hypertensive groups were also matched closely for blood pressure values and for duration of hypertension. In all subjects, after 1 week of a controlled intake of Na and K, the following parameters were measured: urine excretion of Na, K, Ca, Mg, and P, plasma levels of K, Mg, inorganic P, total calcium and ionized calcium, and plasma renin activity, aldosterone concentration, and intact PTH. Blood pressure and laboratory parameters were determined again in all the PA patients after 1 month of 100 mg daily spironolactone administration, and in four out of the 10 PA patients 2 months after surgical removal of aldosterone-producing adenomas. All of these subjects had undergone the same controlled intake of Na and K indicated above. Serum intact PTH was higher in PA patients than in the other three groups (P < .01), and serum ionized calcium was significantly higher in normotensive subjects than in the three hypertensive groups (v PA P < .01, v LREH and v NREH P < .05). An increase in serum ionized calcium and a decrease in PTH level were associated with both spironolactone administration (P < .001) and surgical treatment (P < .05). These results suggest the presence of calcium metabolism alterations in both PA and EH patients, but that these alterations are more exaggerated in PA, so that higher PTH levels are needed for maintaining low-normal levels of serum ionized calcium.

Adrenal Cortex Neoplasms↗
PubMed2004

Effect of spironolactone on endothelial function in patients with congestive heart failure on conventional medical therapy.

We prospectively studied the effect of spironolactone, an aldosterone antagonist, on endothelial function in patients with advanced congestive heart failure (CHF) using the brachial artery reactivity method. Twenty patients optimized on conventional CHF therapy were treated with spironolactone, and brachial artery flow- mediated dilation was measured at baseline and at 4 and 8 weeks. Spironolactone improved endothelial function at 4 weeks, and sustained the improvement at 8 weeks, in patients with CHF on conventional medical therapy, presumably due to reversal of aldosterone impairment of endothelial nitric oxide activity.

Aged↗