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1.
[Spironolactone in resistant essential hypertension].
Lorthioir, A, Belmihoub, I, Fouassier, D, Azizi, M, Amar, L
Presse medicale (Paris, France : 1983). 2019;(12):1431-1438
Abstract
Resistant hypertension is defined as uncontrolled blood pressure (BP) despite three antihypertensive agents including a diuretic (thiazide diuretic if renal function is normal or loop diuretic in case of chronic kidney disease with eGFR<30mL/min), a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, at optimal doses. Resistance must be confirmed by out-of-office measurements (ambulatory blood pressure monitoring or home blood pressure monitoring) and patients should be asked about treatment compliance and excessive salt or alcohol intake. If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for secondary causes of hypertension as they are frequent in this context. If essential resistant hypertension is confirmed, the mineralocorticoid receptor antagonist, spironolactone, should be added (25 to 50mg daily). In the event of a contraindication to spironolactone, or if adverse effects occur, a beta-blocker, an alpha-blocker, or a centrally acting antihypertensive drug should be prescribed.
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Hyperkalemia in ambulant postcardiac surgery patients during combined therapy with angiotensin-converting enzyme inhibitor, spironolactone, and diet rich in potassium: A report of two cases and review of literature.
Dixit, A, Majumdar, G, Tewari, P
Annals of cardiac anaesthesia. 2019;(2):162-168
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Abstract
INTRODUCTION Potassium is the most abundant cation in intracellular compartment. A deficiency or excess of its serum concentration can be deleterious to the one suffering from a cardiac ailment. Post cardiac surgery patients are often on multiple drugs like angiotensin receptor blockers (ARBs), angiotensin converting enzyme inhibitors (ACEI), diuretics including potassium sparing diuretics which are known to predispose for hyperkalemia. We report two postoperative cases who developed life threatening hyperkalemia despite normal renal function due to a combination of factors like treatment with ACEI, potassium sparing diuretics, high dietary intake of potassium and we also discuss renal handling of potassium in this review of literature. METHODOLOGY We present a case series of two cases of cardiac surgery, who presented in the emergency department with hyperkalemia, managed conservatively and detailed history revealed that patient were also on very high nutritional potassium. RESULT Both the patients responded to conservative management and there was no recurrence of such episodes once the dose of diuretics was adjusted and diet modification advised. CONCLUSION In India, many patients are from a low socioeconomic background and often resort to cheap and filling food items like bananas. This dietary factor should be kept in mind while prescribing patients with these medications and adequate counseling regarding diet should be done.
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Interventions for preventing high altitude illness: Part 2. Less commonly-used drugs.
Gonzalez Garay, A, Molano Franco, D, Nieto Estrada, VH, Martí-Carvajal, AJ, Arevalo-Rodriguez, I
The Cochrane database of systematic reviews. 2018;(3):CD012983
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Abstract
BACKGROUND High altitude illness (HAI) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (˜ 8200 feet). Acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude ascent. In this second review, in a series of three about preventive strategies for HAI, we assessed the effectiveness of five of the less commonly used classes of pharmacological interventions. OBJECTIVES To assess the clinical effectiveness and adverse events of five of the less commonly used pharmacological interventions for preventing acute HAI in participants who are at risk of developing high altitude illness in any setting. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) in May 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text search terms. We scanned the reference lists and citations of included trials and any relevant systematic reviews that we identified for further references to additional trials. SELECTION CRITERIA We included randomized controlled trials conducted in any setting where one of five classes of drugs was employed to prevent acute HAI: selective 5-hydroxytryptamine(1) receptor agonists; N-methyl-D-aspartate (NMDA) antagonist; endothelin-1 antagonist; anticonvulsant drugs; and spironolactone. We included trials involving participants who are at risk of developing high altitude illness (AMS or HACE, or HAPE, or both). We included participants with and without a history of high altitude illness. We applied no age or gender restrictions. We included trials where the relevant medication was administered before the beginning of ascent. We excluded trials using these drugs during ascent or after ascent. DATA COLLECTION AND ANALYSIS We used the standard methodological procedures employed by Cochrane. MAIN RESULTS We included eight studies (334 participants, 9 references) in this review. Twelve studies are ongoing and will be considered in future versions of this review as appropriate. We have been unable to obtain full-text versions of a further 12 studies and have designated them as 'awaiting classification'. Four studies were at a low risk of bias for randomization; two at a low risk of bias for allocation concealment. Four studies were at a low risk of bias for blinding of participants and personnel. We considered three studies at a low risk of bias for blinding of outcome assessors. We considered most studies at a high risk of selective reporting bias.We report results for the following four main comparisons.Sumatriptan versus placebo (1 parallel study; 102 participants)Data on sumatriptan showed a reduction of the risk of AMS when compared with a placebo (risk ratio (RR) = 0.43, CI 95% 0.21 to 0.84; 1 study, 102 participants; low quality of evidence). The one included study did not report events of HAPE, HACE or adverse events related to administrations of sumatriptan.Magnesium citrate versus placebo (1 parallel study; 70 participants)The estimated RR for AMS, comparing magnesium citrate tablets versus placebo, was 1.09 (95% CI 0.55 to 2.13; 1 study; 70 participants; low quality of evidence). In addition, the estimated RR for loose stools was 3.25 (95% CI 1.17 to 8.99; 1 study; 70 participants; low quality of evidence). The one included study did not report events of HAPE or HACE.Spironolactone versus placebo (2 parallel studies; 205 participants)Pooled estimation of RR for AMS was not performed due to considerable heterogeneity between the included studies (I² = 72%). RR from individual studies was 0.40 (95% CI 0.12 to 1.31) and 1.44 (95% CI 0.79 to 2.01; very low quality of evidence). No events of HAPE or HACE were reported. Adverse events were not evaluated.Acetazolamide versus spironolactone (1 parallel study; 232 participants)Data on acetazolamide compared with spironolactone showed a reduction of the risk of AMS with the administration of acetazolamide (RR = 0.36, 95% CI 0.18 to 0.70; 232 participants; low quality of evidence). No events of HAPE or HACE were reported. Adverse events were not evaluated. AUTHORS' CONCLUSIONS This Cochrane Review is the second in a series of three providing relevant information to clinicians and other interested parties on how to prevent high altitude illness. The assessment of five of the less commonly used classes of drugs suggests that there is a scarcity of evidence related to these interventions. Clinical benefits and harms related to potential interventions such as sumatriptan are still unclear. Overall, the evidence is limited due to the low number of studies identified (for most of the comparison only one study was identified); limitations in the quality of the evidence (moderate to low); and the number of studies pending classification (24 studies awaiting classification or ongoing). We lack the large and methodologically sound studies required to establish or refute the efficacy and safety of most of the pharmacological agents evaluated in this review.
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Resistant Hypertension and the Pivotal Role for Mineralocorticoid Receptor Antagonists: A Clinical Update 2016.
Epstein, M, Duprez, DA
The American journal of medicine. 2016;(7):661-6
Abstract
True resistant hypertension must be distinguished from apparent resistant hypertension, of which important causes include medication nonadherence, illicit drug use, and alcoholism. Ambulatory blood pressure monitoring should be considered to rule out white coat hypertension. The pathogenesis is multifactorial, but the 2 pivotal factors include volume excess and the myriad effects of aldosterone. Aldosterone increases vascular tone because of endothelial dysfunction and enhances the pressor response to catecholamines. It also plays a crucial role in vascular remodeling of small and large arteries. Aldosterone also promotes collagen synthesis, which leads to increased arterial stiffness and elevation of blood pressure. Because aldosterone has been demonstrated to modulate baroreflex resetting, in cases of severe hypertension, there would be fewer compensatory mechanisms available to offset the blood pressure elevation.
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[Aldosterone antagonists--first choice in resistant hypertension].
Holzgreve, H
MMW Fortschritte der Medizin. 2016;(7):65-6
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Spironolactone for Management of Heart Failure with Preserved Ejection Fraction: Whither to After TOPCAT?
Mitter, SS, Shah, SJ
Current atherosclerosis reports. 2015;(11):64
Abstract
Mineralocorticoid receptor antagonists (MRAs) represent an attractive class of drugs for the treatment of heart failure with preserved ejection fraction (HFpEF) because of the deleterious cardiovascular effects of aldosterone and because MRAs combat myocardial fibrosis and improve cardiac structure/function and vascular health. Recently, the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study, a randomized, double-blind clinical trial of spironolactone versus placebo, was conducted in 3445 patients with symptomatic HFpEF. Although considered by some to be a negative trial, TOPCAT demonstrated that spironolactone decreases heart failure hospitalizations in patients with HFpEF. Furthermore, a pre-specified subgroup analysis of TOPCAT by geographic region uncovered concerning findings from Russia/Georgia, questioning (1) whether the correct patients were enrolled in this region and (2) whether enrolled patients actually received the study drug. In the Americas, spironolactone was clearly superior to placebo in reducing cardiovascular events. Given these data from TOPCAT, basic science evidence for the role of aldosterone in HFpEF, and results from other MRA clinical trials in HFpEF, we advocate using spironolactone in HFpEF with close monitoring of potassium and renal function.
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[Conn's syndrome].
Born-Frontsberg, E, Quinkler, M
Der Internist. 2009;(1):17-26
Abstract
The primary hyperaldosteronism (PHA) is the most prevalent form (8-10%) of secondary causes of hypertension among hypertensive subjects. This will result in 2 to 2.5 million people suffering from PHA in Germany. Screening for PHA should be performed by measuring the aldosterone-renin ratio in the morning. The current antihypertensive medication should be taken into account. A suspicious ratio must lead to a confirmatory test to validate the diagnosis of PHA. For further PHA subtype investigation adrenal imaging is performed using CT or MRI. Adrenal venous sampling is often required to definitively confirm uni- or bilateral aldosterone hypersecretion. The aldosterone-producing adenoma (Conn's syndrome) is primarily cured by endoscopical unilateral adrenalectomy. Bilateral hyperplasia, which is found in two-thirds of primary hyperaldosteronism, is treated primarily by a mineralocorticoid receptor antagonist (12.5-100 mg/day spironolactone). The start of medication should be closely monitored by serum electrolyte and creatinine controls.
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Sodium retention in heart failure and cirrhosis: potential role of natriuretic doses of mineralocorticoid antagonist?
Bansal, S, Lindenfeld, J, Schrier, RW
Circulation. Heart failure. 2009;(4):370-6
Abstract
Patients with cirrhosis and heart failure (HF) share the pathophysiology of decreased effective arterial blood volume because of splanchnic vasodilatation in cirrhosis and decreased cardiac output in HF, with resultant stimulation of the renin-angiotensin-aldosterone system. Hyperaldosteronism plays a major role in the pathogenesis of ascites and contributes to resistance to loop diuretics. Therefore, the use of high doses of aldosterone antagonist (spironolactone up to 400 mg/day) is the main therapy to produce a negative sodium balance in cirrhotic patients with ascites. Hyperaldosteronism also has increasingly been recognized as a risk factor for myocardial and vascular fibrosis. Therefore, low-dose aldosterone antagonists are being used in patients with HF for cardioprotective action. However, the doses (25 to 50 mg/day) at which they are being used in cardiac patients as reported in the Randomized Aldactone Evaluation Study are not natriuretic. It is likely, therefore, that the mortality benefit relates primarily from their effect on cardiac and vascular fibrosis. Resistance to commonly used loop diuretics is frequently present in patients with advanced HF. In patients with decompensated HF with volume overload who are loop diuretic resistant, ultrafiltration may be the only available option. This is, however, an invasive procedure. For these patients, natriuretic doses of aldosterone antagonists (spironolactone >50 mg/day) may be a potential option. The competitive natriuretic response of aldosterone antagonists is related to activity of the renin-angiotensin-aldosterone system: the higher the renin-angiotensin-aldosterone system activity, the higher the dose of aldosterone antagonist required to produce natriuresis. This article will discuss the potential use of natriuretic doses of aldosterone antagonists in patients with HF, including the potential side effect of hyperkalemia.
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[Treatment for symptoms of pseudoaldosteronism].
Shibata, H, Ito, H
Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine. 2007;(4):805-10
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Treatment of premenstrual disorders.
Kroll, R, Rapkin, AJ
The Journal of reproductive medicine. 2006;(4 Suppl):359-70
Abstract
Premenstrual disorders are characterized by a wide variety of affective and somatic symptoms. This diversity of presenting symptoms has led to the use of many different types of treatment approaches, none of which has proven to be successful in all women with these disorders. Non-pharmacologic options include aerobic exercise, dietary changes and supplementation, and cognitive-behavioral therapy. Of the pharmacologic agents used to treat premenstrual symptoms, 3 selective serotonin reuptake inhibitors have received a Food and Drug Administration (FDA) indication for treating premenstrual dysphoric disorder (PMDD). Agents that are often used off label to treat premenstrual symptoms include spironolactone and oral contraceptives (OCs); gonadotropin-releasing hormone (GnRH) agonists and alprazolam are used less frequently in these patients. OCs have historically had little consistent data from controlled clinical trials to support their efficacy until a number of recent studies showed that an OC containing the novel progestin drospirenone is effective in reducing premenstrual symptoms in many women. A new drospirenone-containing OC formulation that is administered for 24 days in a 28-day cycle has been shown to be effective in treating PMDD.