Showing papers on "Spironolactone published in 1990"

Treatment of hirsutism with the pure antiandrogen flutamide

Abstract: The effectiveness of the antiandrogen flutamide in combination with an oral contraceptive was studied in 20 patients with moderate to severe hirsutism. Eight patients had no previous therapy, whereas 12 had failed to respond to oral contraceptives, spironolactone, or dexametha-sone therapy. Treatment with the antiandrogen flutamide (250 mg twice daily) and an oral contraceptive (Ortho 1/35) resulted in a particularly rapid and marked decrease in the total hirsutism score, which reached the normal range at 7 months. Seborrhea, acne, and hair loss score were also rapidly corrected. Treatment was associated with a decrease in plasma luteinizing hormone, progesterone, and estradiol levels. Plasma sex hormone-binding globulin levels were initially low in 18 of 20 patients but increased significantly during therapy. No clinically significant side effects were observed.

Intracerebroventricular infusion of RU28318 blocks aldosterone-salt hypertension

Abstract: The chronic intracerebroventricular (icv) infusion of aldosterone in rats and dogs elevates the blood pressure within 10-14 days at doses far below those that produce hypertension systemically. The effect in rats is dose dependent and blocked by the concomitant icv infusion of the antimineralocorticoid, prorenone. The effect of the icv infusion of RU28318, another specific spironolactone mineralocorticoid antagonist, on the hypertension produced by chronic subcutaneous (sc) administration of aldosterone in sensitized rats was reported. Miniosmotic pumps were used to deliver 1 micrograms/h aldosterone sc and 1.1 micrograms/h RU8318 icv. Over a 24-day period the indirect systolic blood pressure of the control, RU28318 icv, and aldosterone sc plus RU28318 icv groups increased from 105 to 123 mmHg and were not significantly different from each other, whereas the aldosterone sc group increased to 156 mmHg. RU28318, icv or sc, did not alter the increase in urine volume produced by aldosterone sc, and there was no significant differences in weight between the groups. This study provides evidence of the importance of the central nervous system in the pathogenesis of hypertension produced by systemic mineralocorticoid excess.

Apparent mineralocorticoid excess, pseudohypoaldosteronism, and urinary electrolyte excretion: toward a redefinition of mineralocorticoid action.

Abstract: Patients with apparent mineralocorticoid excess (AME) have low or absent activity of the enzyme 11 beta OH steroid dehydrogenase (11SD), and inappropriately high intrarenal levels of cortisol resulting in Na+ retention and hypertension. Pseudohypoaldosteronism (PHA), in contrast, is characterized by salt wasting despite hyperaldosteronemia, reflecting low or absent mineralocorticoid receptors (MR). Although AME is presumed to reflect inappropriate cortisol occupancy of MR, several features also suggest inappropriate occupancy of glucocorticoid receptors (GR). To test this possibility, we administered carbenoxolone, which is known to block 11SD, to four patients with PHA, and observed marked mineralocorticoid effects, e.g., antinatriuresis and elevated plasma bicarbonate. To further test the possibility that occupancy of renal GR may induce a classical mineralocorticoid response, we administered the highly specific glucocorticoid RU 28362 to adrenalectomized rats and showed that it has profound antinatriuretic effects. Finally, by selectively blocking MR with RU 28318 or GR with RU 38486, we have shown that corticosterone, the physiologic glucocorticoid in rats, has an antinatriuretic effect in adrenalectomized rats via either MR or GR occupancy. Previous studies have clearly shown that MR are inherently nonselective and have equivalent intrinsic affinity for aldosterone, corticosterone, and cortisol. The present studies suggest that this nonselectivity includes the nuclear response element to which either MR or GR may bind to elicit a mineralocorticoid effect, and further underscore the importance of the enzyme 11SD in the specific mineralocorticoid action of aldosterone.

Pathogenesis of the type 2 variant of the syndrome of apparent mineralocorticoid excess.

Abstract: The syndrome of apparent mineralocorticoid excess, which is not a primary disorder of the adrenal cortex, describes the association of an unexplained hypermineralocorticoid state with a decreased rate of peripheral 11 beta-hydroxydehydrogenation of cortisol to cortisone. Studies in this syndrome have led to the hypothesis that peripheral cortisol inactivation is the normal mechanism permitting specific mineralocorticoid recognition. This view reconciled developing evidence that the mineralocorticoid receptor itself could not distinguish between mineralocorticoids and glucocorticoids. The syndrome occurs in two forms. In both forms there is decreased turnover of a normal level of plasma cortisol, consistent with the view that delayed removal of the glucocorticoid from strategic receptor sites unmasks its potential mineralocorticoid agonism. In the type 1 variant, impaired 11 beta-hydroxydehydrogenation is reflected by an elevated cortisol/cortisone metabolite ratio. In three patients with the type 2 variant, this ratio was normal, suggesting that the rate of 11 beta-hydroxydehydrogenation was unimpaired. The hypertension and hypokalemic alkalosis of both forms are improved by spironolactone, but patients with the type 2 variant have responded somewhat better to the suppression of cortisol by dexamethasone.

Relation of cardiovascular disease to potassium and magnesium deficiencies

Abstract: Potassium and magnesium deficiencies, particularly those induced by conventional loop and thiazide diuretic therapy, have been linked in clinical studies to an increased frequency in serious arrhythmias and mortality in acute myocardial infarction. Magnesium repletion has been shown not only to increase magnesium levels, but also to increase muscle potassium and to decrease the frequency of ventricular ectopic beats. Potassium replenishment alone may have a detrimental effect in magnesium-depleted patients. The potassium-sparing diuretic spironolactone (Aldactone) has been shown to spare both potassium and magnesium, and may therefore be a more appropriate diuretic therapy in patients at cardiovascular risk.

Role of Aldosterone in the Sodium Retention of Patients with Nephrotic Syndrome

Abstract: The role of aldosterone in the abnormal sodium retention in patients with nephrotic syndrome has been debated. In fact, studies using a converting enzyme inhibitor to lower plasma aldosterone have rej

Traditional management of liver disorders.

Abstract: Dietary measures have achieved mixed results in the management of liver disorders. Although a high energy diet may shorten the course of viral hepatitis by a relatively small amount, dietary restriction is usually of no benefit in compensated cirrhosis. Restriction of sodium intake to 22 to 60 mol/day leads to resolution of cirrhotic ascites in approximately 20% of patients, and reduces the requirement for diuretics in the remainder. In advanced liver disease, diet plays an important role in the avoidance of portal-systemic encephalopathy (PSE), with the tolerance of most nutrients, most importantly protein, being sharply reduced. Despite the frequent presence of carbohydrate intolerance in liver disease, carbohydrate supplementation may be required to ensure adequate utilisation of the reduced dietary protein intake. Zinc supplementation may also be required in liver cirrhosis to compensate for a deficiency. Bed rest is an important component of the management of acute and chronic liver disorders, together with the avoidance of fatigue. Abstinence from alcohol is required in alcoholic liver disease patients, who should receive parenteral thiamine 100 mg and other vitamin and mineral supplementation as required. Agents acting on the ascending loop of Henle [such as furosemide (frusemide)] or the distal tubule (such as spironolactone) are the diuretics most frequently employed to mobilise ascites in cirrhosis, the latter drug being the more effective in nonazotaemic patients. In the absence of oedema, the diuresis should be restricted to a maximum of 750 ml/day; however, patients with oedema may safely undergo a diuresis of less than or equal to 1.5 L/day. Diuretic therapy is often associated with renal complications, such as azotaemia (usually reversible) and severe hyponatraemia in cirrhotic patients with ascites; spironolactone may produce antiandrogenic adverse effects. Lactulose, used in the treatment of acute and chronic PSE, acts by inhibiting gastrointestinal absorption of ammonia and other toxic nitrogenous substances, and by reducing urea degradation. Other pharmacological treatments, such as branched-chain amino acids and benzodiazepine antagonists have a limited role in the management of PSE. Chronic cholestasis has been treated with cholestyramine and fat-soluble vitamins, whereas ursodeoxycholic acid appears to be a promising agent in the treatment of primary biliary cirrhosis. In chronic hepatitis, the prevention of development of cirrhosis is a primary treatment goal which has been attempted with variable success using antifibrotic drugs such as penicillamine and colchicine.(ABSTRACT TRUNCATED AT 400 WORDS)

Quantitative assessment of spironolactone treatment in women with diffuse androgen-dependent alopecia

Abstract: months with spironolactone (75 or 100 mg per day) and six remained untreated. In the untreated (control) group, mean values for total hair density (P 150 mg per day may be necessary to improve hair quality and increase hair density. However, further long-term studies are required to confirm these findings.

Use of spironolactone in treatment of hirsutism.

Abstract: Spironolactone (Aldactone), 100 mg to 200 mg daily, has antiandrogenic effects that may enhance treatment of androgen-excess syndromes, particularly severe hirsutism. Combination therapy with an oral contraceptive or with dexamethasone appears to have a beneficial effect. Side effects are transient. The drug should be avoided during pregnancy and in women who have a family history of breast cancer, although there is no proven association between spironolactone and breast malignancy.

Spironolactone in the management of congestive heart failure

Abstract: Although many new drags 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.

Spironolactone: a re-examination.

Abstract: A review of the aldosterone antagonist spironolactone is presented It is effective both as monotherapy and in combination with other hypotensive agents in the control of both essential and hyperaldosterone-induced hypertension It is useful as a diuretic in conditions such as cirrhosis and congestive heart failure, and is most commonly employed because of its potassium- and magnesium-sparing qualities Spironolactone also has been used as an antiandrogenic agent in managing hirsutism Its adverse effect profile, considered somewhat prohibitive in the past, is generally not significant when reasonably low doses (less than 150 mg/d) are used

Treatment of androgenic disorders in women: acne, hirsutism, and alopecia

Abstract: Androgen excess disorders--acne, alopecia, and hirsutism--can be treated effectively with endocrine therapy such as androgen receptor blockers or antagonists, or with androgen suppression. Spironolactone, estrogen, and dexamethasone are considered the most effective approaches to treatment. Whatever the modality, careful planning is key to success, with recognition that response rates vary from patient to patient. A treatment regimen generally continues for at least 2 years.

Spironolactone versus nifedipine in essential hypertension.

Abstract: In a double-blind, randomized, multicenter study of 194 patients with moderate hypertension, spironolactone and nifedipine were found to reduce blood pressure (BP) to about the same extent and in the same percentage of patients after 45 days of treatment (47 and 50%, respectively). At that point, the patients controlled by either drug continued on their regimen for another 45 days, while patients whose BP was still elevated (diastolic BP greater than 90 mm Hg), received the other drug in addition. After 45 days of combination therapy, 63% of the patients had normal BP, whereas those receiving monotherapy largely remained normotensive (96% in the spironolactone group and 88% in the nifedipine group). The adverse effects were not severe with either group, but the incidence was markedly higher in the nifedipine group.

Prediction of diuretic mobilization of cirrhotic ascites by pretreatment fractional sodium excretion

Abstract: In a randomized prospective study the efficacy and side effects of xipamide versus the combination spironolactone/furosemide in the treatment of cirrhotic ascites were studied. Out of 27 patients four responded to a basic treatment consisting of salt and water restriction and one had to be excluded because of deterioration of kidney function. The remaining 22 patients were randomized to additional treatment with either 20 mg xipamide/day (group I) or 200 mg spironolactone/ day combined with 40 mg of furosemide every other day (group II). A response to treatment during the first 4 days was seen in 7 of 11 patients of group I versus only 3 of 11 patients in group II. In the latter group 7 of 11 patients finally responded after 8 days of treatment. Responsiveness to either diuretic treatment strongly depended on pretreatment fractional Na excretion, FENa. The resistance to diuretic treatment can be predicted by a FENa<0.2%, and could be overcome by additional strategies known to reduce avid proximal Na reabsorption. Xipamide frequently induced hypokalemia, whereas hyperkalemia was seen following treatment with spironolactone/furosemide. Kidney function remained stable during either diuretic treatment.

Peripheral action of spironolactone: plethysmographic studies.

Abstract: 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 Mood flow in finger and calf (representative of skin and muscle circulation) by an etectrocardiographic-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.

Peripheral action of spironolactone: improvement in arterial elasticity.

Abstract: Arterial elasticity, which can be assessed by means of a piezogram, is thought to be involved in the development of hypertension. In hypertensive patients (and with aging in normal subjects), arterial elasticity is reduced. Long-term administration of spironolactone, β blockers, or a β-blocker/dihydralazine combination to hypertensive patients sufficiently reduced systolic and diastolic blood pressure to about the same extent; however, only spironolactone had any effect on piezoelectric indexes of arterial elasticity.

Use of diuretics in the treatment of ascites in patients with cirrhosis

Abstract: The cirrhotic patient with ascites has an increased tubular reabsorption of sodium. Diuretic therapy allows an urinary loss of sodium. The strongest diuretics which inhibit sodium reabsorption in the ascending limb of the loop of Henle (like furosemide) are not the most effective in cirrhotic patients; indeed the increased load of sodium arriving in the distal part of the tubule is reabsorbed because of hyperaldosteronism. Potassium-sparing diuretics, like spironolactone, which act beyond the sites of reabsorption of most of the filtered sodium, are mostly effective when combined with other diuretics which impair sodium reabsorption more proximally. We propose to treat ascites by: 1. Sodium restriction (maximum: 60 mmol per day); 2. Spironolactone 100 to 500 mg per day, combined with furosemide 40 to 200 mg per day if spironolactone does not induce a natriuretic effect.

Spironolactone and altizide used in combination with enalapril: twenty-four-hour ambulatory recording of blood pressure.

Abstract: The addition of enalapril or acebutolol to a regimen of altizide + spironolactone in patients with moderate hypotension was investigated in a multicenter study of S3 patients. The patients underwent semiambulatory 24-hour blood pressure monitoring, especially to observe hypotensive episodes. In the 25 patients uncontrolled with altizide + spironolactone alone, enalapril and acebutolol were about equally effective in reducing blood pressure. The incidence of hypotension was low and comparable for both treatment groups, provided that the initial dose of angiotensin-converting enzyme inhibitor was low (5 mg).

Treatment of acne vulgaris with anti-androgens

Abstract: This study was conducted to compare the relative efficacy of spironolactone and cimetidine in moderately severe acne vulgaris. Fifteen women were treated with spironolactone (100 mg daily) given cyclically, while 14 women were given cimetidine (1400 mg daily) cyclically. The response was evaluated at 12 weeks. Spironolactone produced a good to excellent response in 11 (73. 3%) acne patients while with cimetidine 6 (42.8%) patients showed a good to excellent response. The mean reduction of the non-inflammatory and inflammatory lesion count was 29. 3 + 3. 6 and 9. 7 + 1. 3 respectively with spironolactone and 18.6 + 5.8 and 6.4 + 2.1 respectively with cimetidine. The response of acne vulgaris to spironolactone was superior to that of cimetidine and this difference was statistically significant (p<.05). The side effects were minimal and did not necessitate withdrawal of treatment.

Spironolactone and altizide versus converting enzyme inhibitor (enalapril).

Abstract: The safety and antihypertensive effectiveness of a fixed-dose combination form of spironolactone + altizide (S/A) were compared with those of enalapril, an angiotensin-converting enzyme inhibitor in a randomized, double-blind, parallel-group study of 186 patients with moderate essential hypertension. The 2 treatment groups were comparable in terms of age, gender, duration and severity of hypertension, diastolic blood pressure (BP), serum potassium and creatinine, and 24-hour urinary sodium excretion after a 4-week washout phase. After 8 weeks of treatment, both S/A and enalapril decreased BP significantly and to about the same extent. Enalapril, however, was more effective in decreasing supine diastolic BP in patients younger than age 50, whereas S/A yielded better results in those older than 50. Laboratory values were similar after both drugs were administered, and there were no clinically significant changes. The study demonstrated that S/A safely reduces elevated BP, particularly in older patients.

Hirsutism in a gynaecological context.

Abstract: Investigation of patients presenting with hirsutism to a gynaecological endocrine clinic revealed a high incidence of anovulation, obesity and elevated androgen levels. The underlying abnormality was polycystic ovarian syndrome (PCOS) in the majority of patients. Low levels of sex hormone binding globulin were common; these increased with oestrogen treatment. Treatment with a combined oral contraceptive pill and low dose spironolactone was often effective in reducing symptoms.

Effect of Magnesium and Potassium on Cardiac Function: The Role of Spironolactone

Abstract: P otassium and magnesium are the body's two pri­ mary intracellular cations, both having pro­ found effects on the heart and cardiovascular system as well as various other organ systems. Chronic diuretic therapy results in a net deficiency of both these electrolytes,\" and has been implicated as one mecha­ nism responsible for the propagation of premature ven­ tricular contractions (PVCs) and sudden death. Much of the literature focuses on potassium depletion and ventricular arrhythmias; however, it is crucial also to understand the effects of hypomagnesemia in the evo­ lution of these arrhythmias. DeCarli et al. investigated the effect of hypomag­ nesemia on control of atrial fibrillation and revealed that patients who were hypomagnesemic required twice the

Reversal of andro-genetic alopecia in a male. A spironolactone effect?

Abstract: This 73-year-old white male has been bald since the age of 28. He developed nonA-nonB-induced liver cirrhosis and had been treated with spironolactone for the last 6 years. For the last 3 months, his hair had started to regrow over the scalp. This might be related to the antiandrogenic effect of spironolactone.

Treatment of hirsutism with spironolactone and progestagen combination

Abstract: The antiandrogenic activity of spironolactone was used for treating hirsutism in 76 women, 29 of whom also had acne. Midcycle vaginal bleeding was observed in 21 patients under spironolactone 75 mg per day. This side-effect disappeared after a progestagen administered 10 days each month was added to the treatment. With this combination, spironolactone was well tolerated and effective in treating acne within the first months of administration, but in 61 percent of the patients at least 6 months were required to improve hirsutism.

"Silent" heart failure as observed by a French cardiologist.

Abstract: As the precursor of overt heart failure, with its grim prognosis, “silent” heart failure is a concept that bears examination. The pathophysiology of congestive heart failure and the mechanisms of the impact of hypertension on the development of left ventricular hypertrophy, and silent and overt heart failure are investigated. In addition, the reasons why diuretics, especially potassium-sparing diuretics such as spironolactone, remain the most effective treatment of mild congestive heart failure, and their role in preventing the evolution of silent to overt heart failure are explained.

Clinical update: spironolactone and altizide as monotherapy in systemic hypertension.

Abstract: A large-scale, open, nonrandomized, multicenter, 90-day study of the safety and efficacy of a thiazide diuretic and aldosterone antagonist combination (Aldactazine, 25 mg spironolactone and 15 mg altizide, 1/day) as monotherapy was performed in 946 patients with mild to moderate hypertension (diastolic blood pressure [BP] between 90 and 120 mm Hg). Adverse effects were assessed, and body weight, heart rate, serum potassium, creatinine and uric acid measurements were monitored. On day 45 of the study, BP was normalized (diastolic BP less than or equal to 90 mm Hg) in 72% of the patients. The dose was increased to 2 tablets per day in the patients whose BP did not reach normal levels. By the end of the study, BP was controlled in 83% of the patients. No significant changes were noted in body weight, heart rate or laboratory values; however, treatment had to be discontinued in 6 patients because of hypokalemia (n = 4) or elevated serum creatinine levels (n = 2). Serum uric acid levels were increased in 5.5% of patients. The rate of adverse effects, as reported by the patients, was low (5%). Thus, this study demonstrates that diuretics, especially the combination of a thiazide diuretic and aldosterone antagonist, remain a safe, effective and economical therapy for patients with mild to moderate hypertension.