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https://www.readbyqxmd.com/read/29456800/discovery-and-in-vitro-optimization-of-3-sulfamoylbenzamides-as-romk-inhibitors
#1
Matthew F Sammons, Sujay V Kharade, Kevin J Filipski, Markus Boehm, Aaron C Smith, Andre Shavnya, Dilinie P Fernando, Matthew S Dowling, Philip A Carpino, Neil A Castle, Shannon G Zellmer, Brett M Antonio, James R Gosset, Anthony Carlo, Jerod S Denton
Inhibitors of the renal outer medullary potassium channel (ROMK) show promise as novel mechanism diuretics, with potentially lower risk of diuretic-induced hypokalemia relative to current thiazide and loop diuretics. Here, we report the identification of a novel series of 3-sulfamoylbenzamide ROMK inhibitors. Starting from HTS hit 4 , this series was optimized to provide ROMK inhibitors with good in vitro potencies and well-balanced ADME profiles. In contrast to previously reported small-molecule ROMK inhibitors, members of this series were demonstrated to be highly selective for inhibition of human over rat ROMK and to be insensitive to the N171D pore mutation that abolishes inhibitory activity of previously reported ROMK inhibitors...
February 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29456372/drug-drug-interaction-related-uncontrolled-glycemia
#2
Mohamed Anwar Hammad, Balamurugan Tangiisuran, Abeer Mohamed Kharshid, Noorizan Abdul-Aziz, Yahaya Hassan, Nor Azizah Aziz, Tarek Mohamed Elsayed
Context: The literature of drug-drug interaction (DDI)-related uncontrolled causality, and preventability of DDI-induced UCG (HbA1c >7%) in outpatients glycemia (UCG) among outpatients with Type 2 diabetes mellitus is still limited. Aims: The aim of this study is to identify the prevalence, mechanism, severity, with Type 2 diabetes. Settings and Design: A cross-sectional study was conducted in Penang General Hospital. Methods: A computerized system for DDI checking was used to assess the severity and mechanism of DDIs...
October 2017: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/29455335/evaluating-the-safety-and-tolerability-of-sacubitril-valsartan-for-hfref-managed-within-a-pharmacist-clinic
#3
Elizabeth K Pogge, Lindsay E Davis
OBJECTIVE: The objective of this research was to describe the use of pharmacist-managed sacubitril/valsartan therapy in a multi-center, outpatient cardiac group. BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNi), is a novel agent for the treatment of heart failure. An ARNi is recommended by national guidelines to be used in place of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy for patients who remain symptomatic...
February 17, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/29442351/milk-alkali-syndrome-mas-as-a-complication-of-the-treatment-of-hypoparathyroidism
#4
Agata Skwarek, Janusz Pachucki, Tomasz Bednarczuk, Zuzanna Żurecka, Michał Popow
Milk-alkali syndrome (MAS), characterized by renal failure, metabolic alkalosis and hypercalcemia, is a severe and life-threatening complication of the treatment of hypoparathyroidism. The clinical course is often sudden and is not preceded by any prodromal symptoms. Occurrence does not depend on the duration of hypoparathyroidism treatment, although it is closely related to the applied therapy, especially the dose of calcium carbonate and active vitamin D preparations. Drugs influencing the glomerular filtration rate (angiotensin receptor blockers, sartans, aldosterone receptor antagonists, thiazide diuretics), lack of adequate routine control, changing the calcium carbonate supplementation, dehydration, a diet rich in pH-basic foods (i...
February 14, 2018: Endokrynologia Polska
https://www.readbyqxmd.com/read/29434680/predictors-of-anti-vegf-drug-induced-hypertension-using-different-hypertension-criteria-a-secondary-analysis-of-the-comparz-study
#5
Arduino A Mangoni, Ganessan Kichenadasse, Andrew Rowland, Michael J Sorich
Background: There is inconsistency in the criteria used to define anti-vascular endothelial growth factor (VEGF) drug-induced hypertension (AVEGF-HT) in published studies. It is unknown whether specific patient characteristics similarly predict AVEGF-HT using different criteria. Methods: We assessed the associations between clinical and demographic factors (n = 22) and AVEGF-HT, using six criteria based on predefined on-treatment blood pressure (BP) thresholds or absolute BP elevations versus baseline, in a post hoc analysis of a phase III trial of 1102 patients with renal cell carcinoma (RCC) randomized to pazopanib or sunitinib (COMPARZ study)...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29433578/resistant-hypertension-on-treatment-reshypot-sequential-nephron-blockade-compared-to-dual-blockade-of-the-renin-angiotensin-aldosterone-system-plus-bisoprolol-in-the-treatment-of-resistant-arterial-hypertension-study-protocol-for-a-randomized-controlled-trial
#6
Elizabeth do Espirito Santo Cestário, Letícia Aparecida Barufi Fernandes, Luiz Tadeu Giollo-Júnior, Jéssica Rodrigues Roma Uyemura, Camila Suemi Sato Matarucco, Manoel Idelfonso Paz Landim, Luciana Neves Cosenso-Martin, Lúcia Helena Bonalume Tácito, Heitor Moreno, José Fernando Vilela-Martin, Juan Carlos Yugar-Toledo
BACKGROUND: Resistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney...
February 12, 2018: Trials
https://www.readbyqxmd.com/read/29430198/acute-kidney-injury-and-infections-in-patients-taking-antihypertensive-drugs-a-self-controlled-case-series-analysis
#7
Kathryn E Mansfield, Ian J Douglas, Dorothea Nitsch, Sara L Thomas, Liam Smeeth, Laurie A Tomlinson
Background: The relative risk of acute kidney injury (AKI) following different infections, and whether angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) modify the risk, is unclear. We aimed to determine the risks of hospital admission with AKI following infections (urinary tract infection [UTI], lower respiratory tract infection [LRTI], and gastroenteritis) among users of antihypertensive drugs. Methods: We used UK electronic health records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database...
2018: Clinical Epidemiology
https://www.readbyqxmd.com/read/29421299/impact-of-statin-intake-on-kidney-stone-formation
#8
Andrew J Cohen, Melanie A Adamsky, Charles U Nottingham, Jaclyn Pruitt, Brittany Lapin, Chi H Wang, Sangtae Park
OBJECTIVES: To determine whether statin intake affects nephrolithiasis risk, and whether higher lipid levels correlate with stone risk. Dyslipidemia is a known independent risk factor for urolithiasis, and emerging evidence suggests common biological pathways. Previous work has suggested that statins protect against new stone formation, but these findings have not been verified by other investigators. METHODS: We queried our Institution's Electronic Data Warehouse for all patients who were newly diagnosed with hyperlipidemia between 2009 and 2011, and had never taken a statin drug...
February 5, 2018: Urology
https://www.readbyqxmd.com/read/29412704/with-no-lysine-kinase-4-modulates-sodium-potassium-2-chloride-cotransporter-activity-in-vivo
#9
Andrew Scott Terker, Maria Castaneda-Bueno, Mohammed Zubaerul Ferdaus, Ryan J Cornelius, Kayla J Erspamer, Xiao-Tong Su, Lauren N Miller, James A McCormick, Wen-Hui Wang, Gerardo Gamba, Chao-Ling Yang, David H Ellison
With no lysine kinase 4 (WNK4) is essential to activate the thiazide-sensitive NaCl cotransporter (NCC) along the distal convoluted tubule, an effect central to the phenotype of familial hyperkalemic hypertension. Although effects on potassium and sodium channels along the connecting and collecting tubules have also been documented, WNK4 is typically believed to have little role in modulating sodium chloride reabsorption along the thick ascending limb of the loop of Henle. Yet wnk4-/- mice (knockout mice lacking WNK4) do not demonstrate the hypocalciuria typical of pure distal convoluted tubule dysfunction...
February 7, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29406057/urinary-stone-disease-diagnosis-medical-therapy-and-surgical-management
#10
REVIEW
Wesley W Ludwig, Brian R Matlaga
Clinical suspicion of urolithiasis should be evaluated with low-dose computed tomography as the first-line imaging modality for nonpregnant, adult patients. A period of observation may be appropriate for ureteral stones less than 10 mm, and medical expulsive therapy may be beneficial for facilitating passage of distal ureteral stones. Regardless of stone type, patients should adhere to a low-sodium diet and attempt to achieve a urine volume of more than 2.5 L daily. Individuals with calcium stones should maintain a normal calcium diet, and if stones persist, citrate therapy or thiazide diuretics in the setting of hypercalciuria may be indicated...
March 2018: Medical Clinics of North America
https://www.readbyqxmd.com/read/29405941/renal-impairment-in-hypophosphatasia
#11
J Bacchetta
Renal impairment in hypophosphatasia (HPP) has been described but remains poorly understood: hypercalciuria, nephrocalcinosis and sometimes even chronic kidney failure secondary to chronic hypercalcemia/hypercalciuria or exposure to toxic agents. The objectives of this review are to describe the different renal lesions observed in HPP, and the therapeutic measures that can be applied (in particular, thiazide diuretics).
May 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29403282/two-mutations-in-the-thiazide-sensitive-nacl-co-transporter-gene-in-a-romanian-gitelman-syndrome-patient-case-report
#12
Cristina Gug, Adelina Mihaescu, Ioana Mozos
Background: Gitelman syndrome (GS) is considered as the most common renal tubular disorder, and we report the first Romanian patient with GS confirmed at molecular level and diagnosed according to genetic testing. Patient and methods: This paper describes the case of a 27-year-old woman admitted with severe hypokalemia, slight hypomagnesemia, hypocalcemia, hypocalciuria, metabolic alkalosis, hyperreninemia, low blood pressure, limb muscle weakness, marked fatigue and palpitations...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29402648/treatment-of-cardiovascular-diseases-among-elderly-residents-of-long-term-care-facilities
#13
Anna Kańtoch, Barbara Gryglewska, Jadwiga Wójkowska-Mach, Piotr Heczko, Tomasz Grodzicki
BACKGROUND: The prevalence of cardiovascular diseases among nursing home residents is high but little is known whether pharmacologic therapy recommended by actual medication guidelines is followed by facility's staff. AIM: To evaluate the adherence to actual guidelines for treatment of cardiovascular diseases among older adult residents of long-term care (LTC) facilities. MATERIAL AND METHODS: The cross-sectional study was performed from December 2009 to November 2010 among 189 elderly residents aged ≥60 years in 3 LTC facilities in Poland: 1 long-term care hospital (LTCH) and 2 nursing homes (NHs)...
February 2, 2018: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/29399724/type-2-diabetes-and-thiazide-diuretics
#14
REVIEW
André J Scheen
PURPOSE OF REVIEW: In patients with prediabetes or type 2 diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes. RECENT FINDINGS: These metabolic disturbances are less marked with low-dose thiazides and, in most but not all studies, with thiazide-like diuretics (chlorthalidone, indapamide) than with thiazide-type diuretics (hydrochlorothiazide). In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazides resulted in a significant reduction in cardiovascular events, all-cause mortality, and hospitalization for heart failure compared to placebo and generally were shown to be non-inferior to other antihypertensive agents...
February 5, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29396243/-menopause-hypertension-and-vascular-disease
#15
J M Zilberman
Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists...
January 28, 2018: Hipertensión y Riesgo Vascular
https://www.readbyqxmd.com/read/29376607/-idiopathic-hypercalciuria-diagnosis-and-treatment
#16
Yu V Olefir, A N Yavorskii, D V Butnaru, O V Shatalova, V S Gorbatenko, A S Gerasimenko
Most patients with idiopathic hypercalciuria and calcium nephrolithiasis have a family history of the disease. Idiopathic hypercalciuria is a metabolic abnormality with various causes and developmental pathways. The systematic review describes specific mutations associated with idiopathic hypercalciuria and nephrolithiasis. Detection of these mutations may provide a better understanding of the pathogenesis of this heterogeneous disease and personalize patient management depending on the detected polymorphisms...
December 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/29373638/renal-considerations-in-the-treatment-of-hypertension
#17
Biff F Palmer, Deborah J Clegg
There are renal implications when employing intensive blood pressure control strategies. While this approach provides cardiovascular benefit in patients with and without chronic kidney disease, the impact on renal disease progression differs according to the pattern of underlying renal injury. In the setting of proteinuria, stringent blood pressure control has generally conferred a protective effect on renal disease progression, but in the absence of proteinuria, this benefit tends to be much less impressive...
January 24, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29371419/plasma-potassium-determines-ncc-abundance-in-adult-kidney-specific-%C3%AE-enac-knockout
#18
Emilie Boscardin, Romain Perrier, Chloé Sergi, Marc P Maillard, Johannes Loffing, Dominique Loffing-Cueni, Robert Koesters, Bernard C Rossier, Edith Hummler
The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet...
January 25, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29361671/mechanisms-and-controversies-in-mutant-cul3-mediated-familial-hyperkalemic-hypertension
#19
Mohammed Zubaerul Ferdaus, James A McCormick
Autosomal dominant mutations in Cullin3 (Cul3) cause the most severe form of Familial Hyperkalemic Hypertension (FHHt). Cul3 mutations cause skipping of exon 9 which results in an internal deletion of 57 amino acids from the CUL3 protein (CUL3-∆9). The precise mechanism by which this altered form of CUL3 causes FHHt is controversial. CUL3 is a member of the Cullin-Ring ubiquitin Ligase (CRL) family which mediates ubiquitination and thus degradation of cellular proteins including With-no-lysine [K] kinases (WNKs)...
January 17, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29326859/severe-hyponatremia-presenting-with-minimal-symptoms
#20
Anita Lwanga, Amira Mohamed, Mayank Patel, Andres Serrano
Hyponatremia is a common electrolyte abnormality, however, encountering a patient with serum sodium level below 100 mEq/L and minimal symptoms is unusual. We present the case of an 86-year-old woman who was found to have serum sodium levels of 99 mEq/L. Her only complaint was difficulty in walking. On admission, and throughout her hospital stay, she did not have altered mental status, focal neurological deficits, or adverse outcomes. Her history, blood work, and urine studies pointed towards a diagnosis of thiazide-associated hyponatremia...
November 8, 2017: Curēus
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