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PubMed2000

The effect of combined oral contraception with or without spironolactone on bone mineral density of hyperandrogenic women.

We studied the effect of treatment with combined oral contraception (COC) with or without spironolactone on the bone mineral density (BMD) of hyperandrogenic women. A group of 22 women (group 1) was treated with ethinylestradiol plus desogestrel for 21 days each month for 12 months, while another group of 21 patients (group 2) was treated with ethinylestradiol and desogestrel for 21 days each month plus spironolactone daily for 12 months. There was no statistically significant difference with respect to mean age, body mass index (BMI) and BMD between the two groups of patients before the treatment. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), androstenedione, total testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), prolactin and estradiol were assessed in both groups and no statistically significant difference was found before treatment. Nor was there any statistically significant difference in bone turnover between the two groups. Statistical analysis was performed using the Student's t test for unpaired data to compare age, BMD and biochemical data, and statistical significance was defined as p < 0.05. The BMD before and after 12 months of treatment showed no statistically significant difference between the patients of group 1 and those of group 2, suggesting that both ethinylestradiol plus desogestrel, and ethinylestradiol and desogestrel plus spironolactone daily for 12 months at the given doses do not affect the BMD of the treated women, while the addition of spironolactone improves the efficacy of hirsutism treatment.

Adult↗
PubMed1986

Comparative antiandrogenic potency of spironolactone and cimetidine: assessment by the chicken cockscomb topical bioassay.

Spironolactone and cimetidine are effective antiandrogens in vivo, although they differ by five orders of magnitude in affinity for androgen receptors in vitro. To explore this discrepancy, we directly compared the antiandrogenic potency of these two compounds in vivo using the chicken cockscomb topical bioassay. In this assay, the growth of the androgen sensitive cockscomb of immature chicks after stimulation by various doses of androgen (dihydrotestosterone 5, 20, or 100 micrograms/day sc) is inhibited by antiandrogens in cream vehicle applied topically to the cockscomb itself. At low levels of androgen stimulation (5 micrograms/day), 0.5% topical cimetidine produced maximal suppression of cockscomb growth, while at high levels of androgen stimulation 100 micrograms/day), topical cimetidine in concentrations as high as 4% did not suppress cockscomb growth. In contrast, topical spironolactone in concentrations as low as 0.06% produced maximal inhibition of cockscomb growth at all androgen doses. Using an intermediate androgen dose (20 micrograms/day), the minimally effective antiandrogenic concentration of topical cimetidine was between 0.5 and 1.0%, while that for topical spironolactone was less than 0.001%. We conclude that the chicken cockscomb topical bioassay is a useful method for assessing relative potency of antiandrogens. With this method, spironolactone appears to be at least 500 times as strong an antiandrogen in vivo as cimetidine.

Administration, Topical↗
PubMed1976

Spironolactone and endocrine dysfunction.

Therapy with spironolactone is often associated with estrogenlike side-effects, including impotence and gynecomastia in men and menstrual irregularity in women. Several possible mechanisms by which spironolactone could cause these side-effects have been identified. Spironolactone has been shown to affect both gonadal and adrenal steroidogenesis, to elevate plasma gonadotrophin levels in children, and to act as an antiandrogen at the target tissue level. This conference presents a discussion of how these effects might interact to produce the endocrine side effects associated with spironolactone therapy.

Adolescent↗
PubMedDate not supplied

[Double-blind therapeutic trial of spironolactone in arterial hypertension].

Spironolactone is a diuretic, selective aldosterone, antagonist with its own antihypertensive action which prevents body loss of potassium. Its clinical use has been documented on the treatment of essential arterial hypertension; however, there does not seem to be enough information to form a solid chemical criterion. This work is a clinical evaluation of the antihypertensive effect of the drug using double-blind technic with 41 patients with essential arterial hypertension, all external patients from the Instituto de Cardiología. They were divided in two groups, selected at random, to be able to observe their tensional range with spironolactone every two weeks, during 16 weeks; and using a placebo for the next 16 weeks. On group following this order; and the other one viceversa. After 32 weeks, the results observed show the effect of placebo, as well as spironolactone on arterial pressure and the statistic comparison, states the real antihypertensive effect of the drug on this group of patients. Every day doses were from 300 to 450 mg., and with it there was a rise in seric potassium of an average of 1 mEq/l. The authors suggest that this drug is useful in cases of essential hypertension although its pathway isn't deeply known. Apparently, the antihypertensive effect of spironolactone is not solely on patients with hypertension due to primary aldosteronism. The intervention on various hipertensinogenous factors in relation to its effect are discussed.

Adult↗
PubMed2001

Spironolactone prescribing in heart failure: comparison between general medical patients and those attending a specialist left ventricular dysfunction clinic.

We compared the rate of prescription of low-dose spironolactone among patients with heart failure in a general medical inpatient setting and in a specialist left ventricular (LV) dysfunction clinic. 38% of general medical patients and 72% of patients attending the specialist clinic had been prescribed spironolactone. When contraindications were considered, 54% of patients in the general medical group and 77% of patients in the specialist clinic group were appropriately treated in respect of spironolactone prescribing. Patients attending a specialist LV dysfunction clinic are therefore more likely to be treated with low dose spironolactone, an accepted appropriate treatment for heart failure, than those admitted to general medical and acute geriatric units. Improvement in care for patients with CHF may be achieved either by increasing the use of specialist clinics or by better dissemination of evolving evidence.

Diuretics↗
PubMed1992

Changes in the plasma levels and basic pharmacokinetic parameters of digoxin used in combination with gentamicin, amiodarone and spironolactone.

Digoxin was administered intravenously (0.035 mg/kg b.w.). A prior five-day treatment with gentamicin (100 mg/kg b.w., 10 mg/kg b.w., i.m.), amiodarone (30 mg/kg b.w., s.c.) and spironolactone (10 mg/kg b.w., p.o.) caused elevation of plasma digoxin levels primarily because the alpha half-life was prolonged (t1/2 alpha). In a combined five-day application of digoxin with gentamicin (10 mg/kg b.w., i.m.), and of digoxin with amiodarone, the plasma levels of digoxin rose due to the lengthened beta half-life (t1/2 beta). In administering a combination of digoxin and spironolactone, the plasma digoxin levels dropped, t1/2 alpha decreased and t1/2 beta increased. A 15-day digoxin treatment tested combinations of digoxin, from days eight to 15, with gentamicin (10 mg/kg b.w., i.m.); with amiodarone, or with spironolactone. The digoxin level was elevated with the combinations of digoxin-amiodarone and digoxin-spironolactone: t1/2 alpha was longer in both cases, while t1/2 beta was longer only for the digoxin-amiodarone combination. No changes were found in the creatinine clearance or renal histology of experimental animals after treatment, nor were any deviations found in the values of T3, T4 and TTX.

Amiodarone↗
PubMed2004

The resurrection of spironolactone on its golden anniversary.

The edematous states, specifically those in CHF and cirrhosis of the liver, are associated with excessive aldosterone secretion and represent states of secondary hyperaldosteremia. Aldosterone promotes sodium retention by the renal tubules. Spironolactone, first introduced 50 years ago (1953), blocks the action of aldosterone on renal transport of electrolytes, thus acting as an effective diuretic, and in addition, has potentiating effects on other diuretics, including the thiazides. Spironolactone has undesirable side effects that have limited its clinical use; the most significant are impotence, gynecomastia, and hirsutism. Eplerenone, a recently introduced selective ARA, decreases morbidity and mortality in patients with CHF following MI and has none of the androgenic or estrogenic side effects of spironolactone. Eplerenone is an effective alternative for spironolactone.

Aged↗
PubMed2005

Automatic detection of spironolactone - related adverse drug events.

Due to increasing reports of spironolactone associated life-threatening hyperkalemia, we implemented a rule in our automated event detection system to monitor serum potassium results in patients receiving spironolactone. In 2004, 419 (10.49%) of 3995 admissions at 3 BJC HealthCare hospitals were identified as having hyperkalemia while on spironolactone. For a 9-month period in one facility, 33 of 52 automatically detected potential ADEs had been validated by pharmacists through manual chart review to have spironolactone as a contributing factor (PPV=63.5%).

Adverse Drug Reaction Reporting Systems↗
PubMed1991

A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients.

It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% +/- 0.28% vs. 0.80% +/- 0.50%; p less than 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% +/- 5.8% vs. 23.4% +/- 7.2%; p less than 0.025) than responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Spironolactone and cimetidine in treatment of acne.

In an open therapeutic trial, 50 patients with acne vulgaris were randomly allocated to one of two groups. One group received spironolactone 100 mg daily and the other cimetidine 1.6 g daily for 12 weeks. Clinical severity of acne and sebum excretion decreased significantly at the end of the trial with both drugs, but significantly more with spironolactone. Mean serum levels of testosterone, androstenedione and dehydroepiandrosterone-sulfate decreased significantly with spironolactone but showed no change with cimetidine. Our data suggest that spironolactone may be useful as antiandrogen in the short term therapy of acne vulgaris.

Acne Vulgaris↗
PubMed1986

[Electrophysiologic effects of a spironolactone-altizide combination on the isolated rat heart].

The association of spironolactone and altizide is effective in the treatment of some forms of resistant oedemas. Our aim was to determine whether the renal effects of this association were associated with abnormal cardiac cellular electrophysiological changes. Isolated rat hearts perfused by the retrograde aortic approach and paced at 200 beats per minute were studied. Cardiac cellular activation was measured by floating microelectrodes in the subepicardial layers of the left ventricle. The following parameters were analysed: the duration of the action potential at 25% and 75% of repolarisation (DAP25 and DAP75), the timing and amplitude of the point of rupture of the action potential (T.PR and A.PR), the amplitude of the action potential at 40 ms (A.40). A simultaneous variation of 3 of these parameters was considered to be a significant change. The animals were given an intraperitoneal injection of either 2.5 mg/kg or 10 mg/kg of spironolactone, 0.25 mg/kg or 1 mg/kg of altizide or any association of these two drugs at the given dosages. Spironolactone alone at these dosages did not cause any change in the electrical activation of the rat ventricular myocardial cell. On the other hand, 1 mg/kg of altizide produced a significant increase in the duration of the ventricular action potential at zero potential (DAP25) and during the plateau phase (T.PR and A.40). These changes, which could be related to the potassium metabolism, were abolished when altizide was associated with spironolactone. This is probably a similar effect to that of the prevention of hypokalaemia and low intracellular potassium concentrations when associating a potassium sparing drug with hypokalaemic diuretics.

Action Potentials↗
PubMed1977

[Detection of the optimal dose of spironolactone for the treatment of benign essential hypertension].

The blood pressure lowering effects of spironolactone have been studied in 40 subjects with benign essential hypertension in an attempt to determine the optimum starting dose for the drug. The trial was carried out by the double blind method. In almost all patients 100-400 mg spironolactone caused a signnificant decrease in diastolic and systolic arterial pressure. Present findings indicate that 100-200 mg spironolactone represents the optimum attack dose. The medication caused a significant rise in serum potassium. Other parameters were not affected by the treatment. In conclusion, it would appear that spironolactone--in association with other antihypertensive regiments--may improve the treatment of essential hypertension, especially in patients showing a tendency to hypokalemia and uricemia, and may offer an additional possibility or alternative in the therapy of hypertensive diseases.

Adult↗
PubMedDate not supplied

Effects in animals of chronic administration of spironolactone--a review.

Spironolactone, an aldosterone antagonist, has been found effective in the treatment of certain forms of hypertension, ascites, and edematous conditions. Since patients may receive daily doses of spironolactone for many years, it is important to determine the chronic effects on tissues. This study reviews the tissue changes in rats, dogs, and monkeys receiving spironolactone daily for up to two years. Dose levels were frequently in excess of 100 times the recommended human dose. The pituitary, adrenals, and kidneys of all animals showed no significant changes. Histologic changes were noted in rat livers, thyroid, and male internal genitalia. There were alterations in monkey testes and male mammary glands. This study found no evidence to suggest that spironolactone is tumorigenic or carcinogenic. Species differences in metabolism may account for the diversity of tissue observations.

Animals↗
PubMed1981

[The influence of spironolactone on the concentration of gonadotrophins and gonadal hormones in prostatic hypertrophy (author's transl)].

The authors examined the influence of spironolactone on the concentration of testosterone, 5 alpha - dihydrotestosterone (DHT), progesterone, oestradiol (E2), LH, and FSH in 47 patients with prostatic hypertrophy, aged from 60 to 80 years. The control group consisted of 58 men of the same age. Spironolactone was prescribed at a dose of 100 mg per day for three months. There was a considerable fall in the concentration of testosterone and of DHT and, at the same time, an increase in the concentration of progesterone, E2 and LH. After treatment with spironolactone there was a decrease in the size of the prostate gland. Results obtained show that spironolactone is an effective drug in the treatment of prostatic hypertrophy, since it inhibits androgen metabolism.

Aged↗
PubMed1982

[Spironolactone bodies. Light and electron microscope study apropos of 4 cases of adrenal adenomas with primary hyperaldosteronism].

So-called Spironolactone bodies are reported in four adrenal cortical adenomas that were removed from patients with primary hyperaldosteronism, treated preoperatively with spironolactone. Their morphology is described optically : these round acidophilic cytoplasmic bodies have a laminated appearance that ranges in size from 2 to 20 mu in diameter. Electron microscopy of the zona glomerulosa non adenomatous cells and of adenomatous cells of glomerular type reveals numerous membranes arranged concentrically around a central core. Connections between the endoplasmic reticulum and mitochondria in the cytoplasm of the cell and lining layers of the body are described and analysed. The authors attempt to explain the formation and the increase of the bodies. Correlations appear between the number of spironolactone bodies and duration of administration of spironolactone and total drug dosage. The results are discussed with those of the literature.

Adenoma↗
PubMed1983

[Spironolactone in idiopathic hirsutism, clinical and biological evaluation of treatment].

Ten midly hirsute women with normal serum levels of testosterone were treated with spironolactone (100 mg die), and the effectiveness of this dose-schedule regimen was evaluated after six months of therapy. Hirsutism subsided partly in all women. We estimated however, that in 6 of the 10 women, the clinical benefit was out weighed by the side effects and other drawbacks of a long term therapy and their medication was then stopped 6 months after its initiation. The changes induced on the pituitary function were evaluated by measuring basal serum T3 T4 and basal and stimulated (TRH-LHRH) TSH, PRL, FSH and LH, prior to and after one month of therapy. Spironolactone induced a greater response of TSH to TRH (p less than .025) but no change in T3 T4, PRL, FSH and LH. These data suggest that changes in TSH response are not explained by the speculated intrinsic oestrogenic activity of spironolactone but rather by a selective interaction with TSH secreting cells. We conclude that spironolactone therapy should not be recommended for the large category of normal women complaining of slight increase of facial hair.

Adult↗
PubMedDate not supplied

The effect of spironolactone in hypertensive patients on regular haemodialysis and after renal allotransplantation.

To determine the role of the renin-angiotensin-aldosterone system in the maintenance of hypertension in patients with end stage renal disease, twenty four hypertensive patients were studied on regular haemodialysis treatment (RDT) and after successful kidney transplantation. The first group consisted of nine patients on RDT with their own kidneys in situ, and the second group consisted of nine kidney transplants. All 18 patients were given spironolactone 300 mg daily for three weeks following a control period of the same duration. In addition, three anephric patients on RDT were studied with the above protocol and three other patients on RDT were given the same dose for only six days. Blood pressure (BP), body weight, plasma K-Na, aldosterone and renin activity in all patients, and Na and aldosterone in urine in the second group were measured. In the first group of patients on RDT plasma potassium and renin activity increased significantly but BP remained unchanged. In the second group of transplanted patients plasma potassium, renin activity, and aldosterone were increased and BP diminished significantly. In the group of three anephric patients plasma potassium increased but plasma renin activity remained very low. Finally, in the patients on dialysis who received spironolactone for only six days there was a parallel increase of serum potassium and plasma renin activity. These findings suggest that in patients on RDT spironolactone stimulates renin secretion and potassium retention possibly by an effect on the remaining nephrons and/or the intestinal wall. On the contrary, in the transplanted patients the effect of spironolactone on the renal tubule is capable of producing sodium depletion and fall in BP.

Adult↗
PubMed1983

Influence of food intake on antihypertensive drugs: spironolactone.

A series of studies has been initiated to examine the influence of concomitant food intake on the effects of antihypertensive drugs during long-term therapy. In the present study, the therapeutic effect of spironolactone and the steady-state concentrations of its major, active metabolite canrenone were compared in 10 hypertensive patients after two 60-day periods of spironolactone treatment, 100 mg once daily, prescribed to be ingested before and together with breakfast, respectively. There was no significant difference in the blood pressure and heart rate values during the two treatment periods, and the canrenone levels were similar. As spironolactone can cause gastric irritation, the present findings support the recommendation that spironolactone always be prescribed for once-daily intake together with breakfast.

Adult↗