Showing papers on "Spironolactone published in 1981"
TL;DR: Diuresis should be initiated with one of the two spironolactone regimens and not with furosemide as the sole agent, which required repetitious upward adjustments in dosage and massive KCl supplements.
Abstract: To compare the efficacy of three commonly used diuretic regimens in the treatment of ascites, we randomized 90 patients to three treatment groups: Sequential Spironolactone (spironolactone followed by furosemide if necessary), Combination (spironolactone and furosemide in combination), and Furosemide (furosemide given alone) Diuretics were begun at a low dose by mouth and the dosage increased until a 04-08 kg daily diuresis was achieved The clinical and laboratory findings were comparable for the three experimental groups on admission to the study All three regimens achieved a comparable rate of diuresis To do so was far more difficult with furosemide alone, which required repetitious upward adjustments in dosage and massive KCl supplements The incidence of encephalopathy, hepatorenal syndrome, and marked electrolyte abnormalities was similar for the three treatment groups except that severe hyperkalemia was more frequent on combination therapy We conclude that diuresis should be initiated with one of the two spironolactone regimens and not with furosemide as the sole agent
98 citations
TL;DR: An editorial review attempts to clarify the findings and to determine whether antialdosterones act mainly at the target cell, or through inhibition of aldosterone production, or alternatively by a combination of each effect.
73 citations
TL;DR: It is suggested that HH is an overlooked cause of hyperkalemia, especially in patients whose hyperKalemia is unexplained, and the use of indomethacin and ibuprofen was associated with one case of HH each.
Abstract: To establish the frequency and clinical and biochemical characteristics of hyporeninemic hypoaldosteronism (HH), we reviewed 100 consecutive cases of hyperkalemia (potassium content > 5.3 mEq/L). The most common cause was end-stage renal failure (34%). Other causes included overzealous potassium replacement, spironolactone therapy, hemolysis, acute renal failure, acidosis, thrombocytosis, and Addison's disease. Ten of 19 patients with unexplained hyperkalemia showed suppressed renin (0.12 to 1.3 ng/mL/hr) and aldosterone (5.4 to 21.6 ng/dL) responses to furosemide-posture challenge. Cortisol reserve was normal in HH. Fludrocortisone acetate therapy corrected the hyperkalemia. Other features of HH include low serum bicarbonate content, mild renal insufficiency, diabetes, and advanced age. The use of indomethacin and ibuprofen was associated with one case of HH each. Results suggest that HH is an overlooked cause of hyperkalemia, especially in patients whose hyperkalemia is unexplained.
49 citations
TL;DR: The diagnosis criteria of primary aldosteronism should now be partly modified, as the patient showed pressor responses to infused angiotensin II and norepinephrine which were similar to those in normal men and the cause of this normotension remains to be elucidated.
Abstract: A 23-yr-old male patient with normotensive primary aldosteronism is reported. He complained of muscle weakness, polydipsia, and polyuria. His blood pressure was generally 118/60 to 124/70 mm Hg. Serum sodium, potassium and chloride were 152.2.2, and 108 meq/liter, respectively. Arterial blood pH, glomerular filtration rate, renal plasma flow and circulating plasma and blood volumes were normal, and plasma bicarbonate was normal or elevated. PRA was 0.16 ng/ml.h and did not increase significantly after sodium deprivation, ambulation, and iv furosemide injection. Plasma aldosterone was 64.1 ng/100 ml. He showed pressor responses to infused angiotensin II and norepinephrine which were similar to those in normal men. Adrenal scintiscanning after iv injection of [131I]6 beta-iodomethyl-19-nor-cholesterol during dexamethasone administration showed dense uptake on the right adrenal and minimal uptake on the left. Intravenous infusion of angiotensin III at a rate of 20 ng/kg. min for 30 min did not cause an increase in plasma aldosterone. Serum electrolytes became normal after spironolactone but not after dexamethasone. At surgery, the right adrenal, bearing a benign adenoma, was removed. After surgery, blood pressure was unchanged, but all biochemical abnormalities disappeared. The cause of this normotension remains to be elucidated, but the diagnosis criteria of primary aldosteronism should now be partly modified.
45 citations
TL;DR: Results provide additional evidence that aldosterone, acting alone or in conjunction with other steroids synthesized by the zona glomerulosa, mediates the hypertension and hyporeninemia of dexamethasone-suppressible aldosteronism.
Abstract: Dexamethasone suppressed urinary aldosterone to less than 1.5 µg⁄day in 1-2 days and lowered blood pressure in a woman and in her 2½-yr-old daughter, both of whom have hypertension and hyporeninemia and are members of a kindred with dexamethasone-suppressible aldosteronism. ACTH given for 7 days produced a sustained increase in aldosterone production and a rise in blood pressure in both patients. The abnormal suppression with dexamethasone and further stimulation with ACTH indicate that the aldosteronism is ACTH-dependent in this disorder. The cause of the ACTH-dependence of aldosterone production in this disorder is unknown but may represent continued stimulation rather than the usual (secondary) inhibition by ACTH of 11-hydroxylation and 18-hydroxylation in zone glomerulosa cells. Blood pressure was normal during treatment with spironolactone and during pregnancy, when the action of aldosterone and other similar steroids was presumably blocked by an increased production of progesterone; this suggests th...
37 citations
TL;DR: Study of the renal effects of aspirin and acetaminophen has provided new insight into the way in which the kidneys may use prostaglandins to preserve renal function when it is threatened.
Abstract: • The renal effects of aspirin and acetaminophen are minor. With a major overdose of acetaminophen, uncommonly renal failure may occur that cannot be ascribed to hepatic failure; its mechanism is unknown. Aspirin may cause a transient shedding of renal tubular cells, alterations in urate excretion, inhibition of spironolactone action, and, in certain clinical settings, a reversible decline in renal function manifested as a fall in glomerular filtration that may be accompanied by mild water, sodium, and potassium retention. Active systemic lupus erythematosus, advanced cirrhosis, and chronic renal insufficiency seem to predispose patients to the effects on renal function, and there is direct or indirect evidence in those conditions that prostaglandin synthesis is an important part of the body's attempt to preserve renal blood flow. Study of these effects has provided new insight into the way in which the kidneys may use prostaglandins to preserve renal function when it is threatened. (Arch Intern Med1981;141:343-348)
34 citations
TL;DR: It is concluded that prazosin causes short-term hemodynamic and long-term clinical improvement in patients with intractable heart failure; that spironolactone helps to prevent clinical attenuation but that more detailed studies are required to better characterize the attenuation to vasodilators seen in patientswith congestive heart failure.
34 citations
TL;DR: It is concluded that the addition of spironolactone hastens and enhances the response to standard treatment with digoxin and chlorothiazide in infants with congestive heart failure.
Abstract: The efficacy of treatment with spironolactone for congestive heart failure secondary to congenital heart disease was studied in 21 infants under 1 year of age. All received digoxin and chlorothiazide. In addition, group A (n = 10) was given supplements of potassium and group B (n = 11) received spironolactone. Daily clinical observations of vital signs, weight, hepatomegaly, and vomiting were recorded. Paired t test analysis showed significant reduction in liver size and weight (P less than 0.01) and respiratory rate (P less than 0.05) in group B, and less significant decreases in group A. The incidence of vomiting was slightly lower in group B. We conclude that the addition of spironolactone hastens and enhances the response to standard treatment with digoxin and chlorothiazide in infants with congestive heart failure.
33 citations
TL;DR: Another cause of factitious mineralocorticoid excess is revealed which may be considered in the differential diagnosis of hypokalemic hypertensive syndromes.
32 citations
TL;DR: The effectiveness of the therapy suggests that thiazide‐triamterene treatment may offer an alternative in some patients with primary aldosteronism who do not tolerate spironolactone, and volume depletion and serum potassium concentration could be maintained within the normal range with or without potassium supplements.
Abstract: The hypertension and hypokalemia of primary aldosteronism are related to excessive aldosterone secretion. Spironolactone, an aldosterone antagonist, is used in high doses to treat the disorder, but it may induce a number of side effects that can limit its use. We investigated the feasibility of treating a group of eight patients with hyperaldosteronism with a triamterene-thiazide combination to induce volume depletion and increase serum potassium concentration. All patients responded with normalization or near normalization of blood pressure. Serum potassium could be maintained within the normal range with or without potassium supplements in all but one patient. The effectiveness of the therapy suggests that thiazide-triamterene treatment may offer an alternative in some patients with primary aldosteronism who do not tolerate spironolactone.
28 citations
TL;DR: Reduction in PA and further elevation in its precursors during the second 5-day period of spironolactone therapy suggests inhibition of aldosterone biosynthesis during this phase of treatment in normal man.
Abstract: Spironolactone, a mineralocorticoid antagonist, may also inhibit aldosterone biosynthesis. In vitro studies suggest that spironolactone and its major metabolites inhibit adrenal 18– and llβ-hydroxylase activity. We examined various adrenal corticosteroids and their precursors, plasma renin activity, aldosterone excretion rate, and serum and urine electrolytes in normal subjects before and on days 5 and 10 of spironolactone administration (400 mg/day). Plasma corticosteroids were also examined 60 min after ACTH (Cortrosyn) 0.25-mg iv bolus. RIAs were performed after extensive chromatography; there was no interference of spironolactone and its metabolites in the assays. All studies were performed in supine subjects in metabolic balance on a constant 120-meq sodium intake. Plasma renin activity was increased (P < 0.001) on both days 5 and 10 of spironolactone. Plasma aldosterone (PA) and the aldosterone excretion rate increased (P < 0.01) on day 5 of spironolactone but decreased (P < 0.01) from day 5 to 10. ...
TL;DR: Two women with the polycystic ovary syndrome were treated with bromocriptine in combination with spironolactone and the combined therapy induced a marked reduction of hirsutism, with ensuing ovulation and pregnancy.
TL;DR: The results establish that 7α-thiospironolactone is a tissue metabolite of spironolACTone and may contribute to the therapeutic actions as well as some of the side effects of the parent drug.
TL;DR: 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.
Abstract: 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.
TL;DR: Because hypertension in Conn's syndrome resistant to spironolactone usually also responds poorly to removal of the adenoma, and is difficult to treat with conventional hypotensive agents, the combination of a converting enzyme inhibitor with a potassium conserving diuretic is worthy of trial in such cases.
Abstract: Spironolactone alone in full dosage failed to correct hypertension in a patient with Conn's syndrome and renal impairment, although the previously increased total exchangeable sodium fell to normal and the previously suppressed plasma angiotensin II did not rise above the normal range Addition of the converting enzyme inhibitor captopril reduced plasma angiotensin II to very low levels, with a slight further fall in exchangeable sodium Blood pressure was well controlled Because hypertension in Conn's syndrome resistant to spironolactone usually also responds poorly to removal of the adenoma, and is difficult to treat with conventional hypotensive agents, the combination of a converting enzyme inhibitor with a potassium conserving diuretic is worthy of trial in such cases
Journal Article•
TL;DR: Substitution of spironolactone with bromocriptine induced further amelioration of these symptoms and renewal of ovulatory cycles and these drugs may afford another mode of therapy in patients with polycystic ovary syndrome.
TL;DR: Bumetanide appeared to be as safe and as efficacious as furosemide in controlling edema and hypertension in patients with renal disease.
Abstract: Bumetanide was compared with furosemide in a total of 43 outpatients with edema due to renal disease, selected from three clinics following a uniform protocol. By random selection, 31 patients received 1 to 10 mg/day bumetanide, and 12 received 40 to 400 mg/day furosemide for at least six months. The patients were evaluated clinically, by standard laboratory tests, as well as by ECG, audiometry, eye examination, and mammary examination. Pooled statistical analysis of the results was done. Edema, body weight, and abdominal girth were reduced during both treatments. There was no significant difference in the mean response to the two diuretic agents by the two-sided probability test in the other parameters studied, e.g., supine and standing blood pressure and pulse, serum electrolytes (sodium, potassium, chloride), and uric acid. There were no differences in liver function tests, hematology, or chest x-ray, and no remarkable effects on hearing. Gynecomastia improved in some patients while being treated with bumetanide after spironolactone was discontinued. Adverse reactions in patients on bumetanide which were considered possibly or probably related to the drug were muscle cramps (two patients); and vertigo, headache, muscle pain, urticaria, chest pain, arthritis, dehydration, postural hypotension, and leg cramps (one each). Laboratory abnormalities in both groups were generally those that could be attributed to the pharmacologic action of the diuretics or due to the patients' underlying disease states. No drug-related adverse effects were noted in ECG, ophthalmologic examinations, or chest x-rays. Two patients in the furosemide group had a probably or possibly drug-related loss of hearing sensitivity. In summary, bumetanide appeared to be as safe and as efficacious as furosemide in controlling edema and hypertension in patients with renal disease.
TL;DR: In this article, 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.
Abstract: 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.
TL;DR: Mass action theory could not explain the urinary potassium and log 10 Na/K responses to repeated doses of spironolactone, precluding valid estimation of relative potency for these variables and suggesting that the latter response alone is an unreliable index of overall renal antimineralocorticoid activity.
Abstract: The dose ratio approach was used to define the steady-state relative potency of the competitive mineralocorticoid antagonists prorenoate potassium and spironolactone in six healthy male subjects using fludrocortisone as mineralocorticoid agonist. Log fludrocortisone dose-response relationships in the presence or absence of antagonists did not differ from linearity and parallelism, supporting the theoretical basis of the method. Urinary sodium and plasma potassium responses appeared to behave according to the law of mass action, which made possible estimation of the potency of prorenoate relative to spironolactone on a weight basis— 4.2:1 (95% C.L. 2.7-6.9:1) and 2.68:1 (95% C.L. 0.71–6.57:1, respectively. The steady-state relative potency for sodium excretion was greater than previously estimated after single doses. Mass action theory could not explain the urinary potassium and log 10 Na/K responses to repeated doses of spironolactone, precluding valid estimation of relative potency for these variables and suggesting that the latter response alone is an unreliable index of overall renal antimineralocorticoid activity.
Clinical Pharmacology and Therapeutics (1981) 29, 679–686; doi:10.1038/clpt.1981.95
TL;DR: The observations suggest that spironolactone has actions on vascular reactivity which are not related to aldosterone or to sodium/potassium pumping and may depend on modification of prostaglandin biosynthesis.
TL;DR: The primary cause of the disorder of this patient seems to be a renal defect in the distal tubule in handling sodium and potassium which is similar to that in Liddle's syndrome.
Abstract: A 24-yr-old woman with hypertension, hypokalemic alkalosis, low plasma renin and hypoaldosteronism was studied. Plasma aldosterone, renin and potassium returned to normal and blood pressure fell after sodium restriction or the administration of triamterene. Thiazide therapy also normalized her blood pressure while dexamethasone, spironolactone and furosemide did not improve her symptoms. Plasma aldosterone levels were low and responded poorly to a short term ACTH injection, but responded well to the maximal adrenal stimulation by ACTH-Z. Plasma levels of cortisol, corticosterone and deoxycorticosterone were within the normal range. Adrenal scintigram with 131I-adosterol and abdominal computed axial tomography did not reveal the presence of a sizeable adrenal tumor. In addition, the urinary kallikrein excretion was low after sodium restriction and showed no response to saline infusion. These findings suggest that the excessive secretion of unusual mineralocorticoids may not exist in this case. From these observations and the results of the therapeutic responses to the diuretic agents, we conclude that the primary cause of the disorder of this patient seems to be a renal defect in the distal tubule in handling sodium and potassium which is similar to that in Liddle's syndrome.
TL;DR: The variability in response to spironolactone between patients is such that fixed dose thiazide-spironolACTone combination tablets are unlikely to prevent hypokalaemia reliably.
Abstract: 1 The influence of spironolactone 25, 50, 100 and 200 mg daily, and placebo, on plasma potassium and other variables was examined in a random crossover study of 15 hypertensive patients taking bendrofluazide 10 mg daily. 2 Spironolactone produced significant dose-related increases in plasma potassium and aldosterone, and reductions in plasma sodium and bicarbonate. 3 In 14 compliant patients plasma concentrations of the major metabolite canrenone were related linearly to the dose of spironolactone, and there was less than twofold variation between patients. The plasma canrenone concentration correlated negatively with body weight (r = -0.77, P less than 0.001). 4 The plasma potassium response to spironolactone varied sevenfold between compliant patients. The response correlated negatively with placebo plasma potassium (r = -0.62, P less than 0.02), positively with plasma canrenone (r = +0.55, P less than 0.05), but was unrelated to plasma aldosterone (r = -0.22). In one patient relative resistance to spironolactone was attributed to exaggerated secondary hyperaldosteronism induced by the drug. 5 The variability in response to spironolactone between patients is such that fixed dose thiazide-spironolactone combination tablets are unlikely to prevent hypokalaemia reliably.
TL;DR: It is suggested that the human bioassay employed in this study provides quantitative information which should be predictive of the therapeutic potency of aldosterone antagonists and shows excellent agreement with clinical experience where SC8109 was considered to have one tenth the potency of spironolactone.
Abstract: 1 The potency of single doses of the aldosterone antagonist SC8109 relative to spironolactone in reversing the urinary electrolyte effects of fludrocortisone was examined in a double-blind, balanced, crossover study in six healthy volunteers. 2 For the urinary ratio log10 10Na/K, the relative potency of SC8109; spironolactone on a weight basis was 0.08:1 (95% confidence limits 0.04--0.13:1). 3 The potency of SC8109 relative to spironolactone for natriuresis and antikaliuresis was 0.10:1 and 0.05:1, respectively. 4 The results show excellent agreement with clinical experience where SC8109 was considered to have one tenth the potency of spironolactone. We suggest that the human bioassay employed in this study provides quantitative information which should be predictive of the therapeutic potency of aldosterone antagonists.
01 Jan 1981
TL;DR: Although spironolactone, a specific antagonist of aldosterone’s mineralocorticoid action, normally corrects the metabolic abnormalities of primary aldosteronism, it does not restore blood pressure to normal levels in all cases.
Abstract: A clear role for aldosterone in sustaining hypertension was first described with the syndrome of primary aldosteronism, a condition in which this mineralocorticoid hormone is secreted autonomously by adenomatous or hyperplastic adrenal glands. It has been presumed that this form of hypertension is sustained by aldosterone-mediated sodium and water retention, but there has been no consistent evidence for volume expansion. And, although spironolactone, a specific antagonist of aldosterone’s mineralocorticoid action, normally corrects the metabolic abnormalities of primary aldosteronism, it does not restore blood pressure to normal levels in all cases.