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new anti hypertension drugs

Michelle de Oliveira Pedrosa, Rayssa Marques Duarte da Cruz, Jéssika Oliveira Viana, Ricardo Olímpio de Moura, Hamilton Mitsugu Ishiki, José Maria Barbosa Filho, Margareth F F M Diniz, Marcus Tullius Scotti, Luciana Scotti, Francisco Jaime Bezerra Mendonça
Molecular Hybridization is an approach in rational drug design where new chemical entities are obtained by combining two or more pharmacophoric units from different bioactive compounds into a single molecule. Through this approach, medicinal chemists hope that the new hybrid derivative presents: better affinity and efficacy when compared to the parent drugs; a modified selectivity profile with improvement over pharmacokinetic and pharmacodynamic restrictions; dual or multiple modes of action; reduction of undesirable side effects; decreases in drug-drug interactions; reduced emergence or spread of drug resistance in microorganisms and protozoans; and lower cost...
September 27, 2016: Current Topics in Medicinal Chemistry
Manuela Funke, Thomas Geiser, Otto D Schoch
In 2015, the international guidelines for diagnosis and treatment of pulmonary hypertension (PH) were updated. Group 3 of the current classification includes PH associated with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), other pulmonary diseases with restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, and developmental lung diseases [1]. PH associated with COPD and ILD is common but difficult to manage, as no long-term randomised controlled trial (RCT) has been conducted with specific pulmonary arterial hypertension (PAH) drugs in PH associated with COPD, and the one recent RCT in PH associated with ILD had to be stopped early due to a possible increased risk of death and side effects in the treatment group...
2016: Swiss Medical Weekly
Albertino Damasceno
Hypertension is the main risk factor for morbidity and mortality in the world. In Sub-Saharan Africa, hypertension, previously almost unknown, is now a major risk factor. A paper recently published showed that mean systolic blood pressure is higher in all regions of Africa compared with other parts of the world, and, most important and contrary to what is happening in the rest of the world, it is increasing in the last years. Another important issue that characterises hypertension in Africa is its extremely low level of awareness and consequently low level of control...
September 2016: Journal of Hypertension
Mohan Raizada
Hypertension (HTN) is the most prevalent modifiable risk for cardiovascular disease (CVD) and disorders directly influencing CVD (i.e. obesity, diabetes, chronic kidney disease, obstructive sleep apnea, etc.). About one billion people worldwide have HTN, with American adults having 90% lifetime risk of developing HTN. Despite aggressive campaign for lifestyle changes and advances in drug therapy, HTN remains an immense health, emotional, and economic challenge. This is due, in part, to the fact that ∼50% of HTN patients' blood pressure remains uncontrolled and ∼20% of HTN patients are resistant to or require > antihypertensive drugs...
September 2016: Journal of Hypertension
Rha Seung-Woon, Choi Byoung Geol, Li Hu, Na Jin Oh, Choi Cheol Ung, Park Chang Gyu, Seo Hong Seog, Oh Dong Joo, Kim Yong Hoon, Her Ae-Young, Park Sang-Ho
OBJECTIVE: Recently several studies reported that anti-hypertensive drugs were associated with development of new-onset diabetes mellitus (NODM). However, data on the relationship between detailed prescription types and long-term incidence of NODM are still limited in Asian patients (pts). DESIGN AND METHOD: A total of 3,208 consecutive hypertension pts prescribed with calcium channel blockers (CCB) were enrolled with the exclusion of diabetic pts. Pts were divided into two groups according to the additional prescription of renin angiotensin system (RAS) blockers; 1) the CCB group (n = 1,987) and 2) CCB + RAS group (n = 1,221)...
September 2016: Journal of Hypertension
Rhian M Touyz
Pathophysiological mechanisms contributing to hypertension include endothelial dysfunction and vascular ignalling. These changes are initially adaptive but chronically become maladaptive leading to vascular damage and loss of function. Common to these processes are changes in the characteristics of vascular cells to a pro-infl ammatory, vasoconstrictory and proliferative phenotype, infl uenced by activation of the RAS and oxidative stress. Increased ROS production and decreased cellular antioxidant defense mechanisms, contribute to oxidative stress, which infl uences redox-sensitive Ang II ignalling that promotes vascular injury in hypertension...
September 2016: Journal of Hypertension
Rhian M Touyz
Pathophysiological mechanisms contributing to hypertension include injury to small arteries, characterised by endothelial dysfunction, vascular remodeling, fibrosis and inflammation, (so called hypertensive vascular phenotype). These changes are initially adaptive but in the long term become maladaptive leading to vascular damage and loss of function, particularly important in small resistance arteries, critically involved in the regulation of peripheral vascular resistance and consequently in blood pressure control...
September 2016: Journal of Hypertension
Xuezhong Zhang, Yuqing Zhang, Lisheng Liu, Alberto Zanchetti
OBJECTIVE: There is some debate as to optimal BP goals with antihypertensive treatment derived mostly in post-hoc analysis of large trials. Because there was limited number of subjects and outcomes within the larger study which may cloud the analytical accuracy of the findings. We suggest a new method to estimate the J-curve. DESIGN AND METHOD: Felodipine Event Reduction (FEVER) study randomized 9711 Chinese hypertensive patients to more or less intense anti-hypertensive treatment with 159,844 BP measurements...
September 2016: Journal of Hypertension
Masatsugu Horiuchi
Hypertensive patients have greater chances of such cardiovascular events as stroke, coronary heart disease, heart or renal failure, peripheral artery disease, and dementia. It is also well recognized that diabetes increases the cardiovascular risks in concert with hypertension. Therefore, main goals for an innovation of anti-hypertensive therapy would be to achieve further risk reduction by targeting the functional, metabolic, and structural alterations associated with hypertension. Professors Dzau and Braunwald et al proposed the concept of "the cardiovascular disease continuum" in 1991, and that hypertension may trigger the chain of events, leading to end-stage heart disease; however, this concept was quite new at that time, and there was some discussion whether "the cardiovascular disease continuum" is true or not...
September 2016: Journal of Hypertension
Hong-Rui Zhan, Zhong-Si Hong, Yi-Shen Chen, Hai-Yu Hong, Ze-Bin Weng, Zhang-Bin Yang, Jing-Li Shi, Zhong-Ben Chen
OBJECTIVE: To study a non-drug therapy for hypertension disease by combining percutaneous laser and electric pulse stimulation to acupoint with music, and to test the efficiency of the combining treatment to grade 1 essential hypertension. METHODS: A total of 174 patients with grade 1 essential hypertension were randomly assigned to 3 groups with a random number table after Chinese medicine (CM) syndrome differentiation: the photoelectric and musical treatment group (Group 1, with a self-developed multi-mode audio frequency pulse photoelectric therapeutic apparatus), acupuncture group (Group 2), and oral placebo group (Group 3), 58 cases per group...
September 2016: Chinese Journal of Integrative Medicine
Che-Sheng Chu, Po-Han Chou, Ching-Heng Lin, Chin Cheng, Chia-Jui Tsai, Tsuo-Hung Lan, Min-Wei Huang, Gerald Nestadt
BACKGROUND: Previous research has suggested a link between antidepressants use and the development of cerebrovascular events, but there has never been any study investigating the risk of stroke in obsessive-compulsive disorder (OCD) patients treated with a selective serotonin reuptake inhibitor (SSRI). METHODS: A retrospective observational cohort study was conducted using data from the National Health Insurance Database of Taiwan between the year of 2001 and 2009...
2016: PloS One
Guangrui Yang, Lihong Chen
Nonsteroidal anti-inflammatory drugs (NSAIDs), especially cyclooxygenase-2 (COX-2) selective inhibitors, are among the most widely used drugs to treat pain and inflammation. However, clinical trials have revealed that these inhibitors predisposed patients to a significantly increased cardiovascular risk, consisting of thrombosis, hypertension, myocardial infarction, heart failure, and sudden cardiac death. Thus, microsomal prostaglandin E (PGE) synthase-1 (mPGES-1), the key terminal enzyme involved in the synthesis of inflammatory prostaglandin E2 (PGE2), and the four PGE2 receptors (EP1-4) have gained much attention as alternative targets for the development of novel analgesics...
2016: Oxidative Medicine and Cellular Longevity
Priyadarshani Galappatthy, Yasindu C Waniganayake, Mohomad I M Sabeer, Thusitha J Wijethunga, Gamini K S Galappatthy, Ruvan Ai Ekanayaka
BACKGROUND: Leg edema is a common adverse effect of dihydropyridine Calcium Channel Blockers (CCB) that may need dose reduction or drug withdrawal, adversely affecting the antihypertensive efficacy. Leg edema is reported to occur less often with (S)-amlodipine compared to conventional racemic amlodipine. We aimed to find the incidence of leg edema as a primary outcome and antihypertensive efficacy with (S)-amlodipine compared to conventional amlodipine. METHODS: This prospective, double-blind, controlled clinical trial randomized 172 hypertensive patients, not controlled on beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), to either conventional amlodipine (5-10 mg; n = 86) or (S)-amlodipine (2...
2016: BMC Cardiovascular Disorders
Fumio Sakane, Satoru Mizuno, Suguru Komenoi
Ten mammalian diacylglycerol kinase (DGK) isozymes (α-κ) have been identified to date. Our previous review noted that several DGK isozymes can serve as potential drug targets for cancer, epilepsy, autoimmunity, cardiac hypertrophy, hypertension and type II diabetes (Sakane et al., 2008). Since then, recent genome-wide association studies have implied several new possible relationships between DGK isozymes and diseases. For example, DGKθ and DGKκ have been suggested to be associated with susceptibility to Parkinson's disease and hypospadias, respectively...
2016: Frontiers in Cell and Developmental Biology
Adelaide Maria de Souza Antunes, Rafaela Di Sabato Guerrante, Jorge de Paula Costa Ávila, Flavia Maria Lins Mendes, Iolanda M Fierro
INTRODUCTION: Arterial hypertension affects over one billion people around the world, making the prevention and treatment of this disease vital. Despite the efforts made to develop new antihypertensive drugs, few new therapies have become available. Angiotensin-converting enzyme (ACE) inhibitors have heralded major steps forward in the treatment of arterial hypertension and cardiovascular diseases since the first compound of this class, captopril, was approved for clinical use in 1981...
August 30, 2016: Expert Opinion on Therapeutic Patents
Xiaolu Bao, Weibo Zhu, Weidong Yuan, Xingbo Zhu, Yijia Yan, Hesheng Tang, Zhilong Chen
A series of new angiotensin II (Ang II) receptor 1 antagonists were designed, synthesized and evaluated. All compounds showed nanomolar affinities for the angiotensin II type 1 receptor in radioligand binding assays and could reduce blood pressure significantly in spontaneously hypertensive rats(SHRs). From which, compound 2b displayed higher affinity binding to angiotensin II type 1 receptor at the same order of magnitude to irbesartan with an IC50 value of 1.26 ± 0.08 nM in radioligand binding assays...
November 10, 2016: European Journal of Medicinal Chemistry
Xiaojian Wang, Ling Zhu, Yan Wu, Kai Sun, Ming Su, Liping Yu, Jingzhou Chen, Weiju Li, Jing Yang, Zuyi Yuan, Rutai Hui
Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts adverse stroke outcomes. However, the association of GDF-15 with first-ever stroke in hypertensive patients has not yet been evaluated. The objective of this study was to evaluate the clinical implications of plasma GDF-15 on the development of first-ever stroke in patients with hypertension.In total, 254 patients with hypertension without a history of stroke were included from March 2010 to August 2010 and followed up until June 2013...
July 2016: Medicine (Baltimore)
Herbert M Himmel, Michael Hoffmann
INTRODUCTION: Compound X is a new proprietary antihypertensive agent that induces its pharmacodynamic effect at an approximate plasma Cmax.u of 0.6nmol/L (rat hypertension model). However, Compound X also shows potent off-target activity at PDE-10a (IC50~12nmol/L). Since PDE-10a is expressed predominantly in brain (striatum) and inhibition/knockout of PDE-10a have been reported to result in anti-psychotic effects, we have established the "induced hyperactivity" test for CNS de-risking of Compound X...
September 2016: Journal of Pharmacological and Toxicological Methods
Philip C Robinson, Lisa K Stamp
BACKGROUND: Gout is a common problem that is increasing in prevalence in Australia. It is associated with many serious comorbidities such as hypertension, chronic kidney disease, obesity, diabetes and cardiovascular disease. Recent changes include the way that older drugs are used, as well as newer therapeutics becoming available or in development. OBJECTIVE: The objective of this article is to provide an update on the management of gout. DISCUSSION: Developments in treatment strategies for gout and newer agents to treat gout are discussed in this article...
May 2016: Australian Family Physician
Brenda Armendáriz-Barragán, Nadiah Zafar, Waisudin Badri, Sergio Arturo Galindo-Rodríguez, Dounia Kabbaj, Hatem Fessi, Abdelhamid Elaissari
INTRODUCTION: Plants are a natural source of various products with diverse biological activities offering treatment for several diseases. Plant extract is a complex mixture of compounds, which can have antioxidant, antibiotic, antiviral, anticancer, antiparasitic, antifungal, hypoglycemic, anti-hypertensive and insecticide properties. The extraction of these extracts requires the use of organic solvents, which not only complicates the formulations but also makes it difficult to directly use the extracts for humans...
August 2016: Expert Opinion on Drug Delivery
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