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Spironolactone for hypertension

George Bazoukis, Costas Thomopoulos, Gary Tse, Costas Tsioufis
Although mineralocorticoid antagonists (MRAs) have been proposed as effective fourth-line blood pressure (BP) lowering agents in resistant hypertension, this effect in heart failure is undetermined. In this synthesis of heart failure randomized controlled trials (RCTs), we evaluated the extent of BP lowering following MRA treatment against placebo. We searched Medline and the Cochrane Collaboration Library databases from 1991 to September 2016 for RCTs, in which MRAs were compared with placebo. The quality of RCTs was assessed with Cochrane risk of bias tool...
March 12, 2018: Heart Failure Reviews
Mohammed Benadallah, Oualid Talhi, Fatiha Nouali, Nourredine Choukchou-Braham, Khaldoun Bachari, Artur M S Silva
The present review deals with the progress in medicinal chemistry of spirocyclic compounds, a wider class of natural and synthetic organic molecules, defined as a hybrid of two molecular entities covalently linked via a unique tetrahedral carbon. This spiro central carbon confers to the molecules a tridimensional structurally oriented framework, which is found in many medicinally relevant compounds, a well-known example is the anti-hypertensive spironolactone. Various bioactive natural products possess the privileged spiro linkage and different chemo-types thereof become synthetically accessible since the 20th century...
March 9, 2018: Current Medicinal Chemistry
Charlotte Boughton, David Taylor, Lea Ghataore, Norman Taylor, Benjamin C Whitelaw
We describe severe hypokalaemia and hypertension due to a mineralocorticoid effect in a patient with myelodysplastic syndrome taking posaconazole as antifungal prophylaxis. Two distinct mechanisms due to posaconazole are identified: inhibition of 11β hydroxylase leading to the accumulation of the mineralocorticoid hormone 11-deoxycorticosterone (DOC) and secondly, inhibition of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2), as demonstrated by an elevated serum cortisol-to-cortisone ratio. The effects were ameliorated by spironolactone...
2018: Endocrinology, Diabetes & Metabolism Case Reports
Eduardo M Krieger, Luciano F Drager, Dante M A Giorgi, Alexandre C Pereira, José Augusto Soares Barreto-Filho, Armando R Nogueira, José Geraldo Mill, Paulo A Lotufo, Celso Amodeo, Marcelo C Batista, Luiz C Bodanese, Antônio C C Carvalho, Iran Castro, Hilton Chaves, Eduardo A S Costa, Gilson S Feitosa, Roberto J S Franco, Flávio D Fuchs, Armênio C Guimarães, Paulo C Jardim, Carlos A Machado, Maria E Magalhães, Décio Mion, Raimundo M Nascimento, Fernando Nobre, Antônio C Nóbrega, Antônio L P Ribeiro, Carlos R Rodrigues-Sobrinho, Antônio F Sanjuliani, Maria do Carmo B Teixeira, Jose E Krieger
The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring...
February 20, 2018: Hypertension
P Rossignol, L Juillard
Hypertension is common in patients with chronic renal disease particularly those with diabetes. It is sometimes resistant to the pharmacological treatment. The mineralocorticoid receptor antagonist spironolactone may be indicated here. The mineralocorticoid receptor antagonists have a Class 1, Level A indication for the treatment of heart failure with reduced ejection fraction. There is an associated risk of worsening renal function and of hyperkalemia which does not hinder their clinical benefit. However, an appropriate biological monitoring is warranted, along with potential dose adaptations...
June 2017: Néphrologie & Thérapeutique
Frederick-Anthony Farrugia, Nicolaos Zavras, Georgios Martikos, Panagiotis Tzanetis, Anestis Charalampopoulos, Evangelos P Misiakos, Dimitrios Sotiropoulos, Nikolaos Koliakos
OBJECTIVES: The aim of this study was to present up to date information concerning the diagnosis and treatment of primary aldosteronism (PA). PA is the most common cause of endocrine hypertension. It has been reported up to 24% of selective referred hypertensive patients. METHODS: We did a search in Pub-Med and Google Scholar using the terms: PA, hyperaldosteronism, idiopathic adrenal hyperplasia, diagnosis of PA, mineralocorticoid receptor antagonists, adrenalectomy, and surgery...
January 1, 2018: Endocrine Regulations
Ansha Subramanian, Mangaiarkkarasi Adhimoolam, Suresh Kannan
Aim: Drug-drug interactions (DDIs) are one of the major but preventable cause of adverse drug reaction. Study of prevalence and prediction of DDIs will make the physician easier to provide better patient care and mitigate patient's harm. Hence, the study was planned to evaluate the potential DDIs among medication prescribed to hypertensive patients in our hospital. Materials and Methods: A prospective, cross-sectional study was conducted among the hypertensive patients in medicine (outpatient/inpatient) department over the period of three months in a tertiary care hospital...
January 2018: Perspectives in Clinical Research
Armin Attar, Amir-Abbas Sadeghi, Fatemeh Amirmoezi, Kamran Aghasadeghi
Background: High blood pressure (BP) is a common chronic disease needs long life drug consumption to control. Spironolactone could be used as the fourth-line therapy in patients with resistant hypertension. However, there is no study to determine the effects of low dose spironolactone as a first line therapy in treatment of essential hypertension. The aim of this study is to investigate the effect of low dose spironolactone monotherapy in management of essential hypertension. Methods: In this double blind randomized clinical trial, 40 patients who had stage I essential hypertension were randomly divided into two groups: intervention group received spironolactone 25 milligram once daily for one month and control group received placebo once daily...
January 2018: Acta Cardiologica Sinica
Anna Oliveras, Pedro Armario, Laia Sans, Albert Clarà, Susana Vázquez, Luis Molina, Júlia Pareja, Alejandro de la Sierra, Julio Pascual
Renal denervation and spironolactone have both been proposed for the treatment of resistant hypertension, but their effects on preclinical target organ damage have not been compared. Twenty-four patients with 24-hour systolic blood pressure ≥140 mm Hg despite receiving three or more full-dose antihypertensive drugs, one a diuretic, were randomized to receive spironolactone or renal denervation. Changes in 24-hour blood pressure, urine albumin excretion, arterial stiffness, carotid intima-media thickness, and left ventricular mass index were evaluated at 6 months...
January 5, 2018: Journal of Clinical Hypertension
Sandra Korol, Fannie Mottet, Sylvie Perreault, William L Baker, Michel White, Simon de Denus
BACKGROUND: Spironolactone, a nonselective mineralocorticoid receptor antagonist (MRA), may have a deleterious effect on glycemia. The objective of this review was to assess current knowledge on MRAs' influence (spironolactone, eplerenone, and canrenone) on glucose homeostasis and the risk of diabetes. METHOD: A systematic review was conducted using the Medline database on articles published from 1946 to January 2017 that studied the effects of MRAs on any glucose-related endpoints, without any restrictions regarding the participants' characteristics...
December 2017: Medicine (Baltimore)
Alberto Morganti, Giuseppe Mancia
Resistant hypertension (RH) can be diagnosed if blood pressure (BP) is not controlled with the combination of three antihypertensive drugs, including a diuretic, all at effective doses. Patients affected by this condition exhibit a marked increase in the risk of cardiovascular and renal morbid and fatal events. They also exhibit an increased activity of the sympathetic nervous system which is likely to importantly contribute at the renal and other vascular levels to the hypertensive state. Almost 10years ago renal denervation (RDN) by radiofrequency thermal energy delivery to the walls of the renal arteries was proposed for the treatment of RH...
December 27, 2017: European Journal of Internal Medicine
Kristen Elizabeth DeCarlo, Nidhi Agrawal
A middle-aged woman with obesity, hyperlipidaemia and diet-controlled diabetes was referred for resistant hypertension. Her blood pressure (BP) was uncontrolled on five medications, including a diuretic. Physical exam revealed a systolic ejection murmur, and ECHO demonstrated moderate hypertrophy. Laboratory examination revealed elevated aldosterone level (20.7 ng/dL) and elevated aldosterone:renin ratio (41.4 (ng/dL)/(ng/mL/h)), meeting criteria for primary aldosteronism (PA), and confirmed by saline infusion testing...
December 22, 2017: BMJ Case Reports
Miranda E Good, Yu-Hsin Chiu, Ivan K Poon, Christopher B Medina, Joshua T Butcher, Suresh K Mendu, Leon J DeLalio, Alexander W Lohman, Norbert Leitinger, Eugene J Barrett, Ulrike M Lorenz, Bimal N Desai, Iris Z Jaffe, Douglas Bayliss, Brant E Isakson, Kodi S Ravichandran
Rationale: Resistant hypertension is a major health concern with unknown etiology. Spironolactone is an effective anti-hypertensive drug, especially for patients with resistant hypertension, and is considered by the World Health Organization (WHO) as an "essential" medication. Although spironolactone can act at the mineralocorticoid receptor (NR3C2), there is increasing evidence of mineralocorticoid receptor (MR)-independent effects of spironolactone. Objective: Here, we detail the unexpected discovery that pannexin 1 (Panx1) channels could be a relevant in vivo target of spironolactone...
December 13, 2017: Circulation Research
Patrick Rossignol, Brian Lee Claggett, Jiankang Liu, Orly Vardeny, Bertram Pitt, Faiez Zannad, Scott Solomon
BACKGROUND: Recent evidence suggests that the mineralocorticoid receptor antagonist spironolactone should be the preferred fourth-line antihypertensive treatment in resistant hypertension (RHTN). Whether spironolactone improves blood pressure (BP) control in heart failure with preserved ejection fraction (HFpEF) and RHTN is unknown. METHODS: We identified patients with RHTN, defined as baseline systolic blood pressure (SBP) between 140 and 160 mm Hg on 3 or more medications, in the Americas cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial, in which patients with HFpEF were randomized to spironolactone vs...
March 10, 2018: American Journal of Hypertension
Juping Zhao, Jun Dai, Wenlong Zhou, Haofei Wang, Wenbin Rui, Wei He, Zhe Zhu, Yu Zhu, Danfeng Xu, Fukang Sun
Study about blood pressure variation in the first 24 hours post-operation is limited in patients with adrenal aldosterone-producing adenoma. We aim to evaluate the potential predictors for postoperative hypertension urgency during the first 24 hours after laparoscopic adrenalectomy in patients with aldosterone-producing adenoma. Clinical data of 177 patients with aldosterone-producing adenoma were retrospectively collected from January 2009 to December 2015 and the potential factors that may influence postoperative blood pressure during the first 24 hours after surgery were analyzed...
November 3, 2017: Oncotarget
Senthil Selvaraj, Brian Claggett, Sanjiv J Shah, Inder Anand, Jean L Rouleau, Akshay S Desai, Eldrin F Lewis, Bertram Pitt, Nancy K Sweitzer, Marc A Pfeffer, Scott D Solomon
AIMS: Recent guidelines have advocated for stricter systolic blood pressure (SBP) control in heart failure with preserved ejection fraction (HFpEF), though data regarding the optimal SBP in HFpEF are sparse. METHODS AND RESULTS: We analysed participants from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study with available baseline and 8-week visit SBP data (n = 1645). We related baseline SBP to several efficacy and safety outcomes...
November 16, 2017: European Journal of Heart Failure
Chang-Yeon Kim, Ji Yong Choi, Kee Sik Kim
RATIONALE: Cases of coronary artery fistula having a connection with the cardiac cavity are rare. Here, we report a case in which 2 coronary arteries empty into the left ventricular cavity together. PATIENT CONCERNS: A 63-year-old woman who was diagnosed as having hypertension 20 years prior presented with dyspnea. DIAGNOSES: The coronary angiography revealed coronary artery fistula. INTERVENTIONS: Chest X-ray showed pulmonary edema...
November 2017: Medicine (Baltimore)
Jiao Lu, Hong-Wei Wang, Monir Ahmad, Marzieh Keshtkar-Jahromi, Mordecai P Blaustein, John Hamlyn, Frans H H Leenen
Aims: High salt intake markedly enhances hypertension induced by angiotensin II (Ang II). We explored central and peripheral slow-pressor mechanisms which may be activated by Ang II and salt. Methods and Results: In Protocol I, Wistar rats were infused subcutaneously with low- dose Ang II (150 ng/kg/min) and fed regular (0.4%) or high salt (2%) diet for 14 days. In Protocol II, Ang II -high salt was combined with intracerebroventricular infusion of mineralocorticoid receptor (MR) blockers (eplerenone, spironolactone), epithelial sodium channel (ENaC) blocker (benzamil), angiotensin II type 1 receptor (AT1R) blocker (losartan) or vehicles...
November 8, 2017: Cardiovascular Research
John W Funder
Spironolactone has been marketed for over half a century as a 'potassium-sparing diuretic', used primarily in patients with ascites. With the realization that primary aldosteronism is the most common (5-13%) form of secondary hypertension, it has become widely used as a mineralocorticoid receptor antagonist. More recently, in the wake of the RALES trial, spironolactone in addition to standard therapy has been shown to be very beneficial in heart failure with a reduced ejection fraction. Despite the failure of the TOPCAT trial, spironolactone is being increasingly used in diastolic heart failure (i...
2017: F1000Research
Macarena Alpañés, Francisco Álvarez-Blasco, Elena Fernández-Durán, Manuel Luque-Ramírez, Héctor F Escobar-Morreale
OBJECTIVE: We aimed to compare a combined oral contraceptive (COC) plus the antiandrogen spironolactone with the insulin sensitizer metformin in women with polycystic ovary syndrome (PCOS). DESIGN: We conducted a randomized, parallel, open-label, clinical trial comparing COC (30 μg of ethinylestradiol and 150 μg of desogestrel) plus spironolactone (100 mg/day) with metformin (850 mg b.i.d.) for one year in women with PCOS (EudraCT2008-004531-38). METHODS: The composite primary outcome included efficacy (amelioration of hirsutism, androgen excess and menstrual dysfunction) and cardiometabolic safety (changes in the frequencies of disorders of glucose tolerance, dyslipidemia and hypertension)...
November 2017: European Journal of Endocrinology
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