Showing papers on "Spironolactone published in 1984"

Oral spironolactone improves acne vulgaris and reduces sebum excretion.

Abstract: 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.

Bumetanide. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use.

Abstract: Bumetanide is a potent 'loop' diuretic for the treatment of oedema associated with congestive heart failure, hepatic and renal diseases, acute pulmonary congestion and premenstrual syndrome and in forced diuresis during and after surgery. Bumetanide may be given orally, intravenously or intramuscularly and produces a rapid and marked diuresis, and increased urinary excretion of sodium, chloride and other electrolytes (within 30 minutes) which persists for 3 to 6 hours. Its principal site of action is on the ascending limb of the loop of Henle, with a secondary action on the proximal tubule. Pharmacologically, bumetanide is about 40-fold more potent than frusemide (furosemide), with the exception of its effects on urinary potassium excretion where its potency is lower. Studies in patients with oedema due to congestive heart failure, pulmonary oedema or hepatic disease show that oral or intravenous bumetanide 0.5 to 2 mg/day produces results comparable to those with frusemide 20 to 80 mg/day. In acute pulmonary oedema, intravenous bumetanide produces a very rapid diuresis. Higher doses of bumetanide may be required (up to 15 mg/day) in patients with chronic renal failure or nephrotic syndrome. In these patients muscle cramps are not uncommon with bumetanide, but glomerular filtration rates are unaffected. In most studies, diuretic effects were accompanied by decreased bodyweight, abdominal girth and improvements in a variety of haemodynamic parameters. Comparison of bumetanide with frusemide at a dose ratio of 1 : 40 reveals no significant differences in clinical response with the exception of renal disease, where patients with oedema appear to respond better to bumetanide. Combination with thiazide diuretics enhances the clinical response to bumetanide. Potassium supplements and spironolactone may be beneficial additions to bumetanide where patients at risk of hypokalaemia can be identified. Clinically important side effects are infrequent, with audiological impairment occurring to a lesser extent than with frusemide. Bumetanide thus offers an important alternative to frusemide when a 'loop' diuretic is indicated.

Intracellular Magnesium Loss After Diuretic Administration

Abstract: Diuretic agents influence the renal handling of magnesium, causing increased losses of the ion. Continuing magnesium losses may, in the long term, result in a magnesium deficiency. 296 patients with congestive heart failure or arterial hypertension receiving long term diuretic therapy were studied by skeletal muscle biopsies to assess their magnesium status. 65% of the congestive heart failure patients and 42% of the patients with arterial hypertension were found to have subnormal values for skeletal muscle magnesium. Studies with the potassium-sparing diuretics amiloride, spironolactone and triamterene demonstrate that these drugs significantly increase the muscle magnesium content in patients on long term diuretic treatment for congestive heart failure and/or arterial hypertension--in addition to their well known positive effect on potassium balance.

Primary adrenal hyperplasia: a new subset of primary hyperaldosteronism.

Abstract: The existence of a new subset of primary hyperaldosteronism that combines the morphology of bilateral hyperplasia with the biochemical and therapeutic responses typical of adenoma recently was suggested. The following is the first detailed case report of that subset. The patient had severe hypokalemia and hypertension responsive to spironolactone, and elevated supine plasma aldosterone and 18-hydroxycorticosterone values that did not increase after ambulation. Surgical removal of 75% of both adrenal glands decreased mineralocorticoid levels into the low normal range and allowed the return of normal renin-angiotensin function, although plasma aldosterone was still unresponsive to postural change. Glucocorticoid reserve remained normal. Histology showed bilateral cortical hyperplasia. The results support the existence of a new subset of adrenal hyperplasia, termed primary adrenal hyperplasia, in which biochemical parameters and response to surgery mimic those of adrenal adenomas. The existence of such a sub...

APPARENT MINERALOCORTICOID EXCESS AND DEFICIENT 11β‐OXIDATION OF CORTISOL IN A YOUNG FEMALE

Abstract: SUMMARY A 19-year-old female, known to have had hypertension and hypokalemic alkalosis since the age of 9 months, was found to have suppressed renin, negligible plasma and urinary aldosterone and low plasma levels of other known sodium-retaining steroids. Despite the normal plasma cortisol the urinary excretion of 17-oxosteroids and 17-oxogenic steroids was low as was the cortisol secretion rate, suggesting a diminished metabolic clearance of cortisol. This was confirmed by the demonstration of a prolonged t1/2 of 14C-cortisol. The abnormally high urinary excretion ratios of cortisol to cortisone, tetrahydracortisol to tetrahydrocortisone and 11-hydroxy-aetiocholanolone to 11-oxy-aetio-cholanolone indicate that the diminished cortisol breakdown is the result of deficient 11β-oxidation. Moreover, the urinary excretion of free cortisol was elevated, probably due to diminished tubular reabsorption of cortisol. Hypokalemic alkalosis did not respond to spironolactone, but was partly corrected by amiloride. No response to dexamethasone was observed, but dexamethasone combined with aminogluthetimide normalized blood pressure and serum K. These findings support the involvement of a sodium-retaining, kaliuretic steroid in this rare syndrome.

Serum Cholesterol During Treatment of Hypertension With Diuretic Drugs

Abstract: • Twenty-three men had an increase in serum levels of total cholesterol and triglycerides after starting a diet to lower their serum cholesterol. They had simultaneously started therapy with, or increased the dosage of, chlorthalidone or hydrochlorothiazide for the treatment of hypertension. To evaluate a possible role of the diuretics in the increase in serum lipid concentrations, 11 of the men were randomly allocated to spironolactone therapy for two to four months. After receiving spironolactone, cholesterol levels decreased by 24 mg/dL, whereas cholesterol levels decreased by only 3 mg/dL in the 12 men still receiving chlorthalidone (P (Arch Intern Med1984;144:710-714)

Relation between plasma aldosterone concentration and renal handling of sodium and potassium, in particular in patients with chronic renal failure

Abstract: In normal subjects a relation was found between the log plasma aldosterone concentration (PAC) and the ratio of renal potassium excretion (Uĸ) and sodium delivery to the sodium-potassium exchange site (UNa+ĸ). This relationship was independent of plasma renin activity (PRA). On these grounds, the Uĸ/UNa+ĸ ratio disturbance was considered to be a function of the PAC, and this relation was considered to reflect an altered sensitivity of the distal tubule to aldosterone. In several pathological conditions involving the kidney, the relation between the PAC and Uĸ/UNa+ĸ remained normal while the glomerular filtration rate was within normal limits. Under these conditions, however, the serum potassium concentration had some influence on this relation, in that a low potassium concentration was accompanied by an elevated (though still normal) PAC relative to the Uĸ/UNa+ĸ ratio. The relation was completely abolished when the effect of endogenous aldosterone was impaired by chronic spironolactone administration in patients with essential hypertension. Analysis to these relations in chronic renal disease made it possible to classify them according to the pathophysiological disturbance in question. We conclude that determination of the Uĸ/UNa+ĸ ratio and its relation to the PAC, PRA, and serum potassium level is very useful for the analysis of disorders of potassium metabolism.

Effects of treatment with diuretics on serum lipoproteins.

Abstract: Diuretics, when used for antihypertensive therapy, may also affect lipoprotein metabolism. The following observations were made after 1-12 months of treatment. Various thiazide-type diuretics significantly increased the potentially atherogenic serum low-density lipoprotein cholesterol (LDL-C) and/or very-LDL-C (V-LDL-C) fractions, while the antiatherogenic high-density lipoprotein cholesterol (HDL-C) level was largely unchanged. Certain loop diuretics also increased the LDL-C/HDL-C ratio. Both types of diuretics elevated serum triglyceride (Tg) levels in some, but not all, studies. Levels of LDL-C were increased in diuretic-treated men and in chlorthalidone-treated postmenopausal women, but not in chlorthalidone-treated premenopausal women. Only two diuretics evaluated, indapamide and spironolactone, had no apparent influence on lipoproteins. A tendency for increased Tg levels and lower HDL-C concentrations was apparent during combined thiazide-type diuretic-beta-blocker treatment; these changes resembled those observed during beta-blocker monotherapy. Diuretic-induced increases in LDL-C were prevented or reversed by concomitant beta-blockade, but not by combination treatment with sympatholytics such as reserpine, methyldopa, and clonidine. Prospective studies are needed to clarify the long-term course and the pathogenic and prognostic relevance of lipoprotein changes induced by various diuretics. In the meantime, it is of clinical interest that premenopausal women may be protected from thiazide-induced increases in LDL-C, certain diuretic agents have no significant effect on serum lipoproteins, and beta-blockers may prevent or reverse increases in LDL-C in men and postmenopausal women during diuretic treatment.

Aldosterone-antagonistic steroids

Abstract: Novel spironolactone derivatives characterized by the C 11 - C 12 double bond which have a potent aldosterone-antagonistic activity without causing potassium loss, used alone in diagnosis and improvement of condition of primary aldosteronism, or together with other drugs in treatment of essential or renal hypertension as well as cardiac or renal edema; prepared from 3,17-bis (ethylene-dioxy)-5,11- androstadiene.

Effect of spironolactone on fluid volumes and adrenal steroids in primary aldosteronism.

Abstract: Plasma volume (PV) and extracellular fluid volume (ECF) were determined in 7 patients with essential hypertension (controls) and in 10 patients with primary aldosteronism, while on a high Na diet (342 mEq/day) and on a low Na diet (12 mEq/day). The volume studies were repeated in 6 of the primary aldosteronism patients during treatment with spironolactone for over 3 months. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), cortisol concentration, and serum Na and K concentrations were measured in all patients while on a Na-restricted diet (85 mEq/day) as well as on high-Na and low-Na diets. There were no significant changes in arterial pressure during different Na diets in any groups of patients with essential hypertension, or primary aldosteronism with and without spironolactone therapy. Spironolactone treatment normalized the arterial pressure in patients with primary aldosteronism at all Na intakes. These patients had greater values for PV and ECF than did those with essential hypertension. Spironolactone treatment reduced PV during the low-Na diet, but did not alter it during the high-Na diet. Spironolactone did not produce significant changes in ECF during either the high-Na or low-Na diets. Although there were no changes in PV and ECF in patients with primary aldosteronism due to changes in Na intake, both PV and ECF were significantly less in these patients during spironolactone treatment and in patients with essential hypertension during low-Na intake than during high-Na intake. With primary aldosteronism, PRA was depressed and PAC was elevated when compared to essential hypertension, these were not altered by different Na diets in the patients with primary aldosteronism as they were in those with essential hypertension. During treatment with spironolactone the PRA was restored to normal and showed normal changes with variations in dietary Na, but PAC remained elevated during spironolactone. Plasma cortisol was the same among those with essential hypertension and patients with untreated and spironolactone-treated primary aldosteronism. Serum K was less in untreated primary aldosteronism during all Na diets than in essential hypertension, but during spironolactone it was restored to normal. These results suggest that in primary aldosteronism the reduction in arterial pressure by spironolactone treatment does not occur simply by reductions in body fluid volumes. The long-term treatment of patients with primary aldosteronism with spironolactone does not inhibit the production of aldosterone, possibly because of enhanced activity of the renin-angiotensin system and an increase in serum K.

Effects of potassium on renin and aldosterone

Abstract: The renin-aldosterone system contributes to the regulation of arterial pressure and to the maintenance of sodium and potassium balance. Alterations in plasma potassium concentration have opposite and independent effects on renin secretion by the kidney and on aldosterone secretion by the adrenal gland. Renin secretion tends to be inhibited by hyperkalemia and stimulated by potassium depletion. In contrast, increases of plasma potassium directly stimulate aldosterone secretion. This effect of potassium on aldosterone serves as a protective mechanism against the development of hyperkalemia. Conversely, hypokalemia inhibits aldosterone production. Small changes in plasma potassium have a greater effect on aldosterone than on renin secretion. In patients with essential hypertension, diuretic induced alterations in serum potassium concentrations may affect both renin and aldosterone secretion. We have observed that therapy with a thiazide diuretic results in a reduction of serum potassium and a greater increase in renin activity than therapy with the potassium-retaining diuretic, spironolactone, despite comparable natriuretic responses with both drugs. Conversely spironolactone therapy is associated with a greater increase in aldosterone production. The greater effect of thiazides on renin activity and the greater effect of spironolactone on aldosterone production may be related to the thiazide induced reduction of serum potassium and the spironolactone induced increases of serum potassium.

Inhibition of furosemide-induced kaliuresis in the rat by trilostane, an inhibitor of adrenal steroidogenesis.

Abstract: In rats treated with furosemide, urinary losses of water, sodium and potassium were accompanied by increased circulating levels of aldosterone. Trilostane, an inhibitor of adrenal 3 beta-hydroxysteroid dehydrogenase activity, prevented furosemide-induced hyperaldosteronism which resulted in a partial inhibition of diuretic-induced kaliuresis without a change in sodium and water excretion. Spironolactone, an antagonist of mineralocorticoid action with inherent diuretic activity, produced qualitatively similar effects to those of trilostane on urinary electrolyte excretion in furosemide-treated intact rats. However, mineralocorticoid-induced potassium loss in adrenalectomized rats was not altered by trilostane but was prevented by spironolactone reflecting the direct effect of spironolactone on the kidney. In addition, furosemide-induced kaliuresis in adrenalectomized rats was not prevented by trilostane. Therefore, although both trilostane and spironolactone reduce diuretic-induced potassium loss, spironolactone acts by competing with aldosterone for the mineralocorticoid receptor while trilostane appears to act exclusively by preventing secondary hyperaldosteronism.

Testosterone, 17 Ks, 17 beta E2 FSH-LH variations and hirsutism modifications during spironolactone therapy.

Abstract: The research here reported concerns 9 hirsute women, four of them with PCO and five with idiopathic hirsutism, who underwent treatment with spironolactone. 4 non hirsute hypertensive cases served as control. For one year hair growth, testosterone, 17 Ks, estradiol and gonadotropins behaviours were studied in all of the patients. Results clearly show that the peripherical response (the hair) to the therapy is only just sufficient, and corresponds to a good reduction of the androgenic hormones in blood. However, there is also an LH gonadotropin secretion reduction which is statistically scarcely significant. If the therapeutic response of hair were good, fetal risk could be prevented with safe and contemporaneous contraception. However, since the response is scarcely sufficient, we do not think this therapy is more advisable than other ones.

Potassium-sparing diuretics: interaction with digoxin in elderly men.

Abstract: The effects of two potassium-sparing diuretic combination drugs, triamterene-hydrochlorothiazide and spironolactone-hydrochlorothiazide, were compared with those of two kaliuretic diuretics, hydrochlorothiazide and furosemide, in order to ascertain the effects of those diuretics on concentrations of serum digoxin, serum potassium, and erythrocyte potassium, and to determine whether any of these diuretics should be preferred for patients taking digoxin. It was concluded that in patients for whom potassium depletion may lead to digoxin toxicity, a potassium-sparing diuretic may safely be used in order to reduce potassium excretion and thereby reduce the risk of arrhythmias.

Metabolic effects of high dose amiloride and spironolactone: a comparative study in normal subjects.

Abstract: Amiloride (75 mg daily) and spironolactone (300 mg daily) were given to five normal subjects for 7 days in order to compare metabolic effects at maximal doses. Blood pressure, body weight, Na+ and K+ balance, and plasma concentrations of Na+, K+, active and total renin, angiotensin II, aldosterone, 11-deoxycorticosterone (DOC), 18-hydroxydeoxycorticosterone (18-OH DOC), corticosterone (B), 18-hydroxycorticosterone (18-OH B) and cortisol were measured before and on each day of treatment. Natriuresis and K+ retention were significantly greater with amiloride. Plasma K+ increased from 4.1 +/- 0.2 to 4.9 +/- 0.2 mmol/l (mean +/- s.d.) on amiloride and from 4.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l with spironolactone. Stimulation of renin, angiotensin II, aldosterone and 18-OH B occurred with both drugs but was greater with amiloride in each case. A transient decrease in systolic and diastolic blood pressure was observed after 2 days of spironolactone treatment but not with amiloride. The slope of the regression of aldosterone on angiotensin II during spironolactone treatment was less than that with amiloride, consistent with partial blockade of aldosterone synthesis by spironolactone. These data suggest that the maximum metabolic effects of amiloride exceed those of spironolactone.

Intrarenal sodium handling during chronic spironolactone treatment

Abstract: Intrarenal sodium handling was studied in 8 patients with essential hypertension before spironolactone treatment (200 mg/day), on the 4th day of treatment, and after 3 months of treatment. The results were compared with similar studies with chlorthalidone (50 mg/day). Renal sodium handling was assessed by simultaneous determination of the glomerular filtration rate, sodium, and potassium excretion, and maximal free-water clearance (CH2O). We took CH2O as an index of’distal’ sodium chloride reabsorption from which the proximal sodium reabsorption was calculated. During the first days of spironolactone treatment a natriuresis and increase in urinary flow rate was found. It resulted in a decrease of the extracellular fluid volume amounting to 0.9 liters and a 2.5-fold increase in the plasma renin activity. Potassium excretion showed a small but significant rise. After 3 months, virtually the same degree of volume depletion was found, which was comparable to that obtained after 3 months of chlorthalidone treatment. CH2O, as a fraction of glomerular filtration rate, decreased by 24% both after 3 days and 3 months, whereas proximal sodium reabsorption increased from 87.8 to 90.4% of the filtered load. CH2O, corrected for the ‘distal’ delivery of sodium, decreased from 85.3 to 80.7%. These changes were nearly the same as those found after 3 months of chlorthalidone treatment. It is concluded from these calculated values that spironolactone inhibits sodium chloride reabsorption in the diluting segment of the nephron and that the resulting increase in sodium delivery or urinary flow to the potassium excretory site partly counteracts the blocking effect of spironolactone on this part of the nephron, thus increasing potassium excretion during the acute administration of this drug.

Pharmacology of the steroid regulation of transmitter choice in cultured rat sympathetic ganglia

Abstract: The normally adrenergic rat superior cervical ganglion becomes cholinergic when grown in explant culture. This response is prevented by the physiological glucocorticosteroid, corticosterone, and the mineralocorticoid, aldosterone. The synthetic glucocorticosteroid, RU 26988, was also active in this respect. Progesterone, spironolactone, testosterone and 17 beta-estradiol were all inactive at 10(-6) M, demonstrating the specificity of the response. The response to 10(-7) M corticosterone was not antagonized by a hundred-fold excess of progesterone, testosterone, cortexolone or spironolactone. The response to 10(-7) M aldosterone was antagonized by spironolactone but not by progesterone. The order of potency of the agonists in this study is similar to that described for classical glucocorticoid receptors. The action of aldosterone was antagonized, however, by the mineralocorticoid antagonist, spironolactone. Thus, the steroid response described here may be mediated by both glucocorticoid and mineralocorticoid receptors or, alternatively, by a new glucocorticoid receptor which can be antagonized by a mineralocorticoid antagonist.

Relative potency of prorenoate potassium and spironolactone in attenuating diuretic induced hypokalaemia.

Abstract: The plasma potassium responses to the aldosterone antagonists prorenoate K (10 mg/day and 40 mg/day) and spironolactone (25 mg/day and 100 mg/day) were compared following treatment for 11 days in combination with the diuretic metolazone (25 mg/day) in a double-blind crossover study in twelve healthy men The best estimate of the potency of prorenoate K relative to spironolactone in attenuating metolazone induced hypokalaemia was 56 with 95% confidence limits 24-352 The method employed allowed a statistically valid quantitative comparison of the potassium sparing properties of the mineralocorticoid antagonists after repeated doses and may be useful in the preclinical evaluation of these drugs

Angiotensin II Analogue Infusion Test in Renovascular Hypertension under Low Sodium Intake and under Spironolactone Administration: Is Angiotensin II Analogue Infusion Test Useful in Determining the Mode of Treatment?

Abstract: An angiotensin II antagonist (1-Sar, 8-Ileu-angiotensin II) was infused into 5 hypertensive patients with unilateral renal artery stenosis under 5-day low sodium diet (2 g NaCl/day) and under 7-day spironolactone administration (300 mg/day). In the sodium depleted state, 1 case showed depressor response, 2 cases pressor response and the other 2 no response. During the spironolactone administration, 3 cases showed depressor, 1 case pressor, and another case no response. Angiotensin II analogue (A II A) infusion test under spironolactone administration was more effective than under sodium depletion. However, there were cases which showed pressor response, i.e. false negative, under low sodium diet and under spironolactone administration. The hypertension of these patients was cured by converting enzyme inhibitor, percutaneous transluminal renal angioplasty (PTRA) or bypass surgery. A II A infusion test has been used for screening, diagnosis and determination of the surgical repair of renovascular hypertension. However, the proportion of depressor response was low in our cases, yet pressor responders and non-responders were also cured by PTRA. PTRA is a painless and low risk procedure of the treatment of renovascular hypertension, so PTRA will become the preferential mode of therapy for the treatment of renovascular hypertension of the cases with no depressor response by AIIA infusion.