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Patients with obstructive sleep apnea (OSA) often have hypertension that is difficult to control. We review the causes of OSA hypertension and evidence supporting specific therapies.
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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.
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Analyses were done on 55 patients treated with spironolactone and 56 patients treated with placebo. Significant reductions of office systolic BP (-8.9±6.7 mmHg, P=0.012), 24-h ABPM systolic BP (-7.9±7.2 mmHg, P=0.032) and ABPM day-time systolic BP (-7.5±7.1 mmHg) after 8 weeks of spironolactone treatment, compared to placebo, were only observed in patients with a median age>62 years. The office and ABPM systolic BP reductions in patients aged ≤62 years and diastolic BP reductions by spironolactone in both age groups were not significant compared to placebo. Women tended to have a nonsignificantly higher reduction in systolic BP with spironolactone treatment, and there was no difference in diastolic BP reduction between women and men.
Medical treatment with a mineralocorticoid receptor (MR) antagonist, which has produced spontaneous remission of bilateral primary aldosteronism (PA), may also produce spontaneous remission of unilateral PA, for which laparoscopic adrenalectomy is recommended. However, few reports exist regarding spontaneous remission after MR antagonist therapy in unilateral PA.
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Patients with congestive heart failure (CHF) often have increased aldosterone activity that leads to hypomagnesemia. Hypomagnesemia can induce arrhythmias, an important cause of death in patients with CHF. We determined whether the aldosterone receptor antagonist spironolactone improved magnesium homeostasis and reduced arrhythmias in patients with CHF.
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Thirty-two women with PCOS were divided into two groups: 16 received 100 mg spironolactone and 16 spironolactone plus 3.5 g of licorice a day. Blood pressure, body mass index, serum electrolytes, plasma renin activity, plasma aldosterone and cortisol, serum testosterone, and urinary tetrahydrocortisol/tetrahydrocortisone ratio were measured before and during treatment.
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The pharmacokinetics and bioavailability of IS-5-MN after single-dose oral and intravenous application were investigated over 24 h in three patients with liver cirrhosis and compared with normal subjects. The analysis of IS-5-MN in plasma was carried out using a gas-chromatographic method with electron capture detection. A two-compartment open model was taken as a basis for the calculations of the plasma concentration curves and the pharmacokinetic parameters. First results show that plasma concentrations after intravenous administration in the patient group were not higher than in the control group. After oral administration the peak concentrations of IS-5-MN were also no higher, nor did they occur earlier, in patients with liver cirrhosis than in the normal subjects. Our data also show the same complete absolute bioavailability of IS-5-MN in the patient group as in normal subjects, and the same elimination half-life of the plasma concentration response curve. We saw no influence of typical comedication, i.e., cimetidine or spironolactone on pharmacokinetic parameters in the group of liver patients.
This study shows that spironolactone may effectively reduce proteinuria in patients with CKD. Concerns remain in regard to the risk for hyperkalemia in patients with CKD. Prospective randomized trials are necessary to confirm the efficacy and safety of antagonists of aldosterone on proteinuria and progression of CKD.
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Outcome of dilated cardiomyopathy (DCM) has markedly improved due to ACE-inhibitors, beta-blockers and implantable defibrillators over the last decades. Aims were both the determination of current mortality rates and the improvement of left ventricular function over time with regard to different baseline factors.
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The findings of this exploratory study strongly suggest that aldosterone promotes oxidative stress and that the administration of spironolactone reduces the production of urinary H2O2 as a result of lesser formation of surrogate reactive oxygen species secondary to the ischemia-reperfusion phenomenon.
Heart failure (HF) is the only cardiovascular disease with increasing incidence and prevalence. Most HF patients are older adults. With the aging of the population and effective treatment of hypertension and coronary artery disease, the two major underlying causes of HF, the number of older Americans with HF is expected to rise significantly in the coming decades. HF is the number one hospital discharge diagnosis for older adults. It is one of the causes of frequent hospital readmissions, reflecting acute decompensation and compromised quality of life for patients and increased cost and resource use for the healthcare system. It is also associated with approximately 300,000 deaths annually, most in older adults. Advances in the management of HF in the past several decades have significantly decreased the mortality and morbidity associated with this condition. Randomized controlled trials have demonstrated the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, beta-blockers, and spironolactone on survival and quality of life of HF patients, but there is evidence of underuse of evidence-based care for HF. Several national guidelines have been published since 1994 that recommended evidence-based evaluation and management of HF. In 1995, the American College of Cardiologists (ACC) and the American Heart Association (AHA) published their first HF guidelines that recommended left ventricular (LV) function evaluation for all patients presenting with HF and use of ACE inhibitors for all patients with LV systolic dysfunction (LVSD) unless contraindicated. The guidelines recommended the use of hydralazine and isosorbide dinitrate in patients who could not use ACE inhibitors. In addition, digoxin was recommended in patients with HF due to LVSD but not adequately responsive to ACE inhibitors and diuretics and in those with atrial fibrillation and rapid ventricular rates. Diuretic use was recommended for symptomatic patients with evidence of fluid overload. Use of anticoagulation was restricted to patients with atrial fibrillation or to those with a history of systemic or pulmonary embolism. Beta-blockers were reserved for HF patients after acute myocardial infarctions. Recent advances in the management of HF called for a revision of the guidelines.
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We retrospectively examined 170 patients with prior MI. The primary end point was cardiac death or hospitalization for heart failure. During a mean follow-up period of 6.4 ± 2.9 years, 37 patients developed the primary end point. Univariate Cox proportional hazards regression analyses showed that age, male gender, chronic kidney disease, anterior wall MI, number of leads with fQRS, left ventricular ejection fraction, loop diuretic use, and spironolactone use were significantly associated with the primary end point. A multivariate Cox proportional hazards regression analysis selected age (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.04-1.14, p<0.001) and the number of leads with fQRS (HR 1.33, 95% CI 1.11-1.60, p=0.002) as predictors of the primary end point. A receiver operating characteristic curve analysis showed that the presence of ≥3 leads with fQRS was most useful for distinguishing between patients with and without the primary end point. A Kaplan-Meier analysis showed a lower primary event-free rate in patients with ≥3 leads with fQRS than in those with <3 leads with fQRS.
During phase A, mean SBP decreased from baseline by 8 mm Hg, and diastolic blood pressure (DBP) decreased by up to 3.8 mm Hg; no dose-response relationship was demonstrated. Mean differences in SBP from placebo during phase B were -2.61 for the low-dose group, +2.32 for the middle-dose group, and -2.76 mm Hg for the high-dose group; only the reduction in the high-dose group was statistically significant (P = .048). No significant effects on DBP of eplerenone therapy relative to placebo were detected. Eplerenone was well tolerated, with a rate of adverse events comparable to that of placebo.
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Treatment-resistant depression patients show both reduced glucocorticoid receptor function and a hyperactive hypothalamic-pituitary-adrenal axis. However, few studies have examined the role of the mineralocorticoid receptor. This study aimed to evaluate the functional activity of the mineralocorticoid receptor system in regulating the hypothalamic-pituitary-adrenal axis in well-defined treatment-resistant depression patients.
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The effect of plasma aldosterone on progression of carotid total plaque area (TPA) was studied using multiple linear regression, with variables that have previously been shown to maximally explain TPA variation (age, sex, total cholesterol, systolic blood pressure, diabetes, smoking, and medication for cholesterol and systolic blood pressure).
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At 12 months, the increase in mean total cholesterol levels was greater in the OC+SPL group than in the OC group (27% vs. 13%, respectively; p=.02). The increase in mean sex hormone-binding globulin levels was greater in the OC group than in the OC+SPL group (424% vs. 364%, respectively; p=.01). No statistically significant differences between the groups were found for any of the other variables.
Plasma IL-21 concentrations were measured in 100 patients (age 58.9 ± 12.0 years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46 h) and again at 24 weeks; cardiac magnetic resonance and measurement of B-type natriuretic peptide, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-2, -3, -9, and tissue inhibitor of metalloproteinase (TIMP)-1, -2, -4 occurred at both time-points. Remodelling was defined as change in LV end-systolic volume index (ΔLVESVI).
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Retrospective analysis of clinical pharmacokinetic data.
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Myocardial RF signals analyzed with chaos theory reflect the severity of LV fibrosis. Aldosterone blockade may alter myocardial ultrasonic texture with regression of LV fibrosis, at least partly through enhanced collagen degradation.
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Minimal invasive adrenalectomy has become the procedure of choice to treat adrenal tumors with a benign appearance, ≤ 6 cm in diameter and weighing < 100 g. Authors evaluated medium- and long-term outcomes of laparoscopic adrenalectomy (LA), performed for ten years in a single endocrine surgery unit.
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Spironolactone is a renal competitive aldosterone antagonist. One of its most important metabolite is the 7α-methylthio spironolactone: thus it is very important to have an efficient and safe access to this compound, for pharmacokinetic studies. In this context, we synthesized this metabolite by thioalkylation of 7α-thio spironolactone using Hünig's base with a very good yield. We also used our procedure to prepare, with an easy work-up and high yields, 7α-thioether and thioester derivatives of spironolactone, that could be useful for further Structure-Activity Relationships studies.
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Treatment with spironolactone (SPL) is beneficial in patients with severe congestive heart failure (CHF). In the Randomized Aldactone Evaluation Study SPL was well tolerated, particularly with regard to renal function and serum K(+) levels. Our aim was to investigate whether the reported low frequency of adverse effects during SPL treatment in a heart failure study population could be confirmed in an unselected heart failure outpatient cohort and to identify potential predictors of harmful effects.
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The relation between breast cancer and selected nonestrogenic drugs was evaluated in the Group Health Cooperative of Puget Sound, Seattle, Washington, a prepaid health care organization with computerized information on diagnoses and outpatient drug use. No important positive associations with breast cancer were found in a follow-up study of 302 women aged 35-74 years. These women were newly diagnosed with breast cancer in 1977-1980 and were studied in relation to exposure in the six months prior to diagnosis to one or more of the following drugs: diazepam, digitalis glycosides, medroxyprogesterone acetate, methyldopa, metronidazole, phenothiazines, tricyclic antidepressants, thiazides, thyroid/levothyroxine sodium, or spironolactone. A modest association between recent reserpine use and breast cancer was present (risk ratio = 1.7, 90% confidence interval 0.9-3.3).
Our experimental study showed that in a dose related manner SP has successful inhibitory effect on the rat uterine horn, and also on the smooth muscle organs; ileum and trachea. We guess that SP can be used in well regulated dosed with least side effects to arrest preterm labor on human being in the future. Up to date there is no manuscript about contraction inhibitory effect of SP on the uterus. We hope this study will be of scientific help.