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Sample records for angiotensin-receptor blocker telmisartan

  1. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial

    DEFF Research Database (Denmark)

    NN, NN; Yusuf, S; Teo, K

    2008-01-01

    BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular...... of cardiovascular death, myocardial infarction, or stroke. FUNDING: Boehringer Ingelheim....

  2. Induction of human adiponectin gene transcription by telmisartan, angiotensin receptor blocker, independently on PPAR-γ activation

    International Nuclear Information System (INIS)

    Moriuchi, Akie; Yamasaki, Hironori; Shimamura, Mika; Kita, Atsushi; Kuwahara, Hironaga; Fujishima, Keiichiro; Satoh, Tsuyoshi; Fukushima, Keiko; Fukushima, Tetsuya; Hayakawa, Takao; Mizuguchi, Hiroyuki; Nagayama, Yuji; Abiru, Norio; Kawasaki, Eiji; Eguchi, Katsumi

    2007-01-01

    Adiponectin, an adipose tissue-specific plasma protein, has been shown to ameliorate insulin resistance and inhibit the process of atherosclerosis. Recently, several reports have stated that angiotensin type 1 receptor blockers (ARBs), increase adiponectin plasma level, and ameliorate insulin resistance. Telmisartan, a subclass of ARBs, has been shown to be a partial agonist of the peroxisome proliferator-activated receptor (PPAR)-γ, and to increase the plasma adiponectin level. However, the transcriptional regulation of the human adiponectin gene by telmisartan has not been determined yet. To elucidate the effect of telmisartan on adiponectin, the stimulatory regulation of human adiponectin gene by telmisartan was investigated in 3T3-L1 adipocytes, utilizing adenovirus-mediated luciferase reporter gene-transferring technique. This study indicates that telmisartan may stimulate adiponectin transcription independent of PPAR-γ

  3. Attenuation of Immune-Mediated Renal Injury by Telmisartan, an Angiotensin Receptor Blocker and a Selective PPAR-γ Activator

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    Yuki Hamano

    2011-09-01

    Full Text Available Background/Aims: Anti-glomerular basement membrane (GBM nephritis is characterized by activation of the renin-angiotensin system. This study aimed to determine the question of whether a temporary angiotensin II blockade at the initial stage of anti-GBM nephritis is able to attenuate the disease as well as differences in renoprotection among angiotensin II receptor blockers (ARBs with distinct peroxisome proliferator-activated receptor (PPAR-γ-modulating activities. Methods: C57BL/6J mice were immunized with rabbit IgG, followed by intravenous injection of rabbit anti-mouse antibodies. Mice were then treated with telmisartan, losartan, and telmisartan + GW9662 (a PPAR-γ antagonist for 5 days, or hydralazine for 9 days. On days 8 and 13, mice were sacrificed to obtain tissues for histological analysis. Results: The temporary administration of telmisartan significantly suppressed glomerular damage compared to hydralazine. Losartan showed a similar effect but was less effective. Co-administration of GW9662 attenuated the renoprotective effect of telmisartan, almost to levels observed with losartan. In particular, it limited the decreased infiltration of inflammatory cells and preservation of capillaries in the glomeruli induced by telmisartan. Conclusion: Temporary angiotensin II blockade at the initial stage of anti-GBM disease dramatically inhibited its progression. In addition to a class effect of ARBs, telmisartan modified inflammation and endothelial damage in the kidney through its PPAR-γ-agonistic action.

  4. Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke

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    Kikuchi, Kiyoshi; Tancharoen, Salunya; Ito, Takashi; Morimoto-Yamashita, Yoko; Miura, Naoki; Kawahara, Ko-ichi; Maruyama, Ikuro; Murai, Yoshinaka; Tanaka, Eiichiro

    2013-01-01

    Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs. PMID:24065095

  5. Reappraisal of role of angiotensin receptor blockers in cardiovascular protection

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    Ram CV

    2011-05-01

    Full Text Available C Venkata S RamTexas Blood Pressure Institute, Clinical Research Institute of Dallas Nephrology Associates; and Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USAAbstract: Angiotensin-converting enzyme inhibitors (ACEIs and angiotensin receptor blockers (ARBs have shown cardioprotective and renoprotective properties. These agents are recommended as first-line therapy for the treatment of hypertension and the reduction of cardiovascular risk. Early studies pointed to the cardioprotective and renoprotective effects of ARBs in high-risk patients. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET established the clinical equivalence of the cardioprotective and renoprotective effects of telmisartan and ramipril, but did not find an added benefit of the combination over ramipril alone. Similar findings were observed in the Telmisartan Randomized AssessmeNt Study in aCE INtolerant subjects with cardiovascular Disease (TRANSCEND trial conducted in ACEI-intolerant patients. In ONTARGET, telmisartan had a better tolerability profile with similar renoprotective properties compared with ramipril, suggesting a potential clinical benefit over ramipril. The recently completed Olmesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial (ORIENT and Olmesartan and Calcium Antagonists Randomized (OSCAR studies will further define the role of ARBs in cardioprotection and renoprotection for high-risk patients.Keywords: angiotensin receptor blockers, hypertension, outcomes, clinical trials

  6. ANGIOTENSIN RECEPTOR BLOCKERS WITH PLEIOTROPIC PROPERTIES: A NEW STANDARD IN CARDIOVASCULAR RISK MANAGEMENT AND TREATMENT OF HYPERTENSION

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    V. I. Podzolkov

    2017-01-01

    Full Text Available An increase in the activity of the renin-angiotensin-aldosterone system is one of the most important mechanisms for the realization of the cardiovascular continuum. The role that angiotensin receptor blockers play in achieving target figures of blood pressure and reducing cardiovascular risk is discussed. The importance of pleiotropic properties of angiotensin receptor blockers (in particular, activation of peroxisome proliferator-activated receptors gamma – PPAR-γ in the management of patients with insulin resistance, obesity, dyslipidemia is also covered. The evidence base for the use of telmisartan as a drug with pleiotropic effect in patients with arterial hypertension and associated diseases (diabetes mellitus, obesity, renal dysfunction is discussed. 

  7. Angiotensin receptor blockers & endothelial dysfunction: Possible correlation & therapeutic implications

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    Miroslav Radenkovic

    2016-01-01

    Full Text Available The endothelium is one of the most important constituents of vascular homeostasis, which is achieved through continual and balanced production of different relaxing and contractile factors. When there is a pathological disturbance in release of these products, endothelial dysfunction (ED will probably occur. ED is considered to be the initial step in the development of atherosclerosis. This pathological activation and inadequate functioning of endothelial cells was shown to be to some extent a reversible process, which all together resulted in increased interest in investigation of different beneficial treatment options. To this point, the pharmacological approach, including for example, the use of angiotensin-converting enzyme inhibitors or statins, was clearly shown to be effective in the improvement of ED. One of many critical issues underlying ED represents instability in the balance between nitric oxide and angiotensin II (Ang II production. Considering that Ang II was confirmed to be important for the development of ED, the aim of this review article was to summarize the findings of up to date clinical studies associated with therapeutic application of angiotensin receptor blockers and improvement in ED. In addition, it was of interest to review the pleiotropic actions of angiotensin receptor blockers linked to the improvement of ED. The prospective, randomized, double-blind, placebo or active-controlled clinical trials were identified and selected for the final evaluation.

  8. Management of hypertension: Insights into prescribing behavior with focus on angiotensin receptor blockers

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    S Ramakrishnan

    2017-01-01

    Full Text Available Introduction: Angiotensin receptor blockers (ARBs are emerging as an attractive first choice antihypertensive as recommended by various guidelines. However, choice among the first-line antihypertensive classes and among ARBs differs between practicing physicians. Aims: This survey aimed to understand the usage preferences of ARBs and its place in for treating hypertension (HTN among physicians from various clinical settings in India. Methods: A cross-sectional survey was conducted with a prevalidated survey questionnaire consisting of 25 questions for HTN management. Practicing general physicians and cardiologists were approached for seeking their perception, opinions, and prescribing behavior. Results: Responses of 594 physicians and cardiologists were received. As opined by 90.1% of physicians, newly diagnosed HTN represented more than 10% of their overall patient load. As a monotherapy, 59.9% of the physicians preferred ARB as the first choice in newly diagnosed HTN patients, followed by calcium channel blocker (12.3% and angiotensin-converting-enzyme inhibitor (8.1%. Of all ARBs, telmisartan is preferred by 73% of physicians. Most physicians prefer telmisartan among all ARBs for 24 h blood pressure (BP control, including morning BP surge (76.4% and for prevention of cardiovascular morbidity and mortality (78.8% followed by olmesartan and losartan. Predominantly, majority of physicians (89.1% agreed for the beneficial role of telmisartan in preventing onset of microalbuminuria and nephropathy. Conclusion: Indian physicians prefer ARBs as the first choice in most hypertensive patients, which shows agreement with the guideline recommendations followed globally. Telmisartan has emerged as the most preferred ARB among all, for most of the HTN patients including those with comorbidities.

  9. Differential clinical profile of candesartan compared to other angiotensin receptor blockers

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    Zimlichman R

    2011-12-01

    Full Text Available Relu Cernes1,2, Margarita Mashavi1,3, Reuven Zimlichman1,31The Brunner Institute for Cardiovascular Research, Wolfson Medical Center and Tel Aviv University, Tel Aviv, Israel; 2Department of Nephrology, Wolfson Medical Center, Holon, Israel; 3Department of Medicine, Wolfson Medical Center, Holon, IsraelAbstract: The advantages of blood pressure (BP control on the risks of heart failure and stroke are well established. The renin-angiotensin system plays an important role in volume homeostasis and BP regulation and is a target for several groups of antihypertensive drugs. Angiotensin II receptor blockers represent a major class of antihypertensive compounds. Candesartan cilexetil is an angiotensin II type 1 (AT[1] receptor antagonist (angiotensin receptor blocker [ARB] that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. Oral candesartan 8–32 mg once daily is recommended for the treatment of adult patients with hypertension. Clinical trials have demonstrated that candesartan cilexetil is an effective agent in reducing the risk of cardiovascular mortality, stroke, heart failure, arterial stiffness, renal failure, retinopathy, and migraine in different populations of adult patients including patients with coexisting type 2 diabetes, metabolic syndrome, or kidney impairment. Clinical evidence confirmed that candesartan cilexetil provides better antihypertensive efficacy than losartan and is at least as effective as telmisartan and valsartan. Candesartan cilexetil, one of the current market leaders in BP treatment, is a highly selective compound with high potency, a long duration of action, and a tolerability profile similar to placebo. The most important and recent data from clinical trials regarding candesartan cilexetil will be reviewed in this article.Keywords: angiotensin receptor blockers, candesartan, candesartan cilexetil, clinical trials, efficacy studies, safety, blood pressure

  10. Angiotensin Receptor Blockers: Cardiovascular Protection in the Metabolic Syndrome

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    Prakash C Deedwania

    2006-03-01

    Full Text Available It is well recognised that the metabolic syndrome, a constellation of risk factors including obesity, hypertension, insulin resistance and dyslipidaemia, is associated with an increased risk of cardiovascular complications and the development of Type 2 diabetes. Consequently, timely identification and management of all components of the metabolic syndrome is warranted. In particular, guidelines have emphasised the importance of targeting elevated blood pressure (BP and dyslipidaemia as a method of reducing global cardiovascular risk.Findings from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE trial show that the angiotensin receptor blocker, valsartan, reduces cardiovascular events and the development of Type 2 diabetes in high-risk individuals. This profile is being further explored in the ongoing Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR trial.Given the potential advantages to patients and physicians of tackling more than one of the components of the metabolic syndrome, antihypertensive agents such as valsartan would appear to be an important addition to the management of vulnerable patients at high risk of cardiovascular events.

  11. Review of ongoing initiatives to improve prescribing efficiency in China; angiotensin receptor blockers as a case history.

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    Zeng, Wenjie; Gustafsson, Lars L; Bennie, Marion; Finlayson, Alexander E; Godman, Brian

    2015-02-01

    Pharmaceutical expenditure is rising by 16% per annum in China and is now 46% of total expenditure. Initiatives to moderate growth include drug pricing regulations and encouraging international non-proprietary name prescribing. However, there is no monitoring of physician prescribing quality and perverse incentives. Assess changes in angiotensin receptor blocker (ARB) utilization and expenditure as more generics become available; compare findings to Europe. Observational retrospective study of ARB utilization and expenditure between 2006 and 2012 in the largest hospital in Chongqing district. Variable and low use of generics versus originators with a maximum of 31% among single ARBs. Similar for fixed dose combinations. Prices typically reduced over time, greatest for generic telmisartan (-54%), mirroring price reductions in some European countries. However, no preferential increase in prescribing of lower cost generics. Accumulated savings of 33 million CNY for this large provider if they adopted European practices. Considerable opportunities to improve prescribing efficiency in China.

  12. A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention

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    Ji-Guang Wang

    2009-07-01

    Full Text Available Ji-Guang WangCentre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaAbstract: Stroke is a leading cause of death and disability worldwide. The importance of lowering blood pressure for reducing the risk of stroke is well established. However, not all the benefits of antihypertensive treatments in stroke can be accounted for by reductions in BP and there may be differences between antihypertensive classes as to which provides optimal protection. Dihydropyridine calcium channel blockers, such as amlodipine, and angiotensin receptor blockers, such as valsartan, represent the two antihypertensive drug classes with the strongest supportive data for the prevention of stroke. Therefore, when combination therapy is required, a combination of these two antihypertensive classes represents a logical approach.Keywords: stroke, angiotensin, calcium channel, cerebrovascular, hypertension, blood pressure

  13. Clinical Evidence for the Cardiovascular Benefits of Angiotensin Receptor Blockers

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    Georg Nickenig

    2006-03-01

    Full Text Available Targeting the renin-angiotensin-aldosterone system (RAAS, specifically the effector peptide angiotensin II (Ang II, represents a major opportunity for slowing the progression of cardiovascular disease (CVD and, in turn, reducing the risk of morbidity and mortality. Inhibition of angiotensin-converting enzyme (ACE and selective blockade of Ang II AT1 receptors are two approaches through which the pathophysiological effects of Ang II can be targeted. Numerous clinical studies have established the benefits of ACE inhibitors P, (ACE-Is in lessening the morbidity and mortality burden of CVD. There are, however, tolerability concerns associated with ACE-Is, such as angioedema and dry cough. By blocking Ang II at the AT1 receptor level, Ang II receptor blockers (ARBs provide a more specific and complete blockade of the deleterious effects of Ang II and tend to have more favourable tolerability. A number of clinical trials have shown that ARBs are not only associated with positive outcomes across the CVD continuum but may also have a role in the prevention or delay of diabetes (a major cardiovascular risk factor. Ongoing trials are aiming to define the place of such agents in lessening morbidity and mortality from CVD.

  14. Individual long-term albuminuria exposure during angiotensin receptor blocker therapy is the optimal predictor for renal outcome

    NARCIS (Netherlands)

    Kröpelin, Tobias Felix; de Zeeuw, Dick; Holtkamp, Frank Arjan; Packham, David Kenneth; Heerspink, Hiddo J. L.

    Albuminuria reduction due to angiotensin receptor blockers (ARBs) predicts subsequent renoprotection. Relating the initial albuminuria reduction to subsequent renoprotection assumes that the initial ARB-induced albuminuria reduction remains stable during follow-up. The aim of this study was to

  15. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers

    DEFF Research Database (Denmark)

    Lambers Heerspink, Hiddo J; Holtkamp, Frank A; Parving, Hans-Henrik

    2012-01-01

    Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis...... of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin-angiotensin-aldosterone system (non-RAASi)-based antihypertensive therapy. Treatment effects on renal and cardiovascular outcomes were compared in subgroups based on dietary sodium intake...... during treatment, measured as the 24-h urinary sodium/creatinine ratio of 1177 patients with available 24-h urinary sodium measurements. ARB compared to non-RAASi-based therapy produced the greatest long-term effects on renal and cardiovascular events in the lowest tertile of sodium intake. Compared...

  16. Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b

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    Lee Robert E

    2006-01-01

    Full Text Available Abstract Background There have been indications that common Angiotensin Receptor Blockers (ARBs may be exerting anti-inflammatory actions by directly modulating the immune system. We decided to use molecular modelling to rapidly assess which of the potential targets might justify the expense of detailed laboratory validation. We first studied the VDR nuclear receptor, which is activated by the secosteroid hormone 1,25-dihydroxyvitamin-D. This receptor mediates the expression of regulators as ubiquitous as GnRH (Gonadatrophin hormone releasing hormone and the Parathyroid Hormone (PTH. Additionally we examined Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma, which affects the function of phagocytic cells, and the C-CChemokine Receptor, type 2b, (CCR2b, which recruits monocytes to the site of inflammatory immune challenge. Results Telmisartan was predicted to strongly antagonize (Ki≈0.04nmol the VDR. The ARBs Olmesartan, Irbesartan and Valsartan (Ki≈10 nmol are likely to be useful VDR antagonists at typical in-vivo concentrations. Candesartan (Ki≈30 nmol and Losartan (Ki≈70 nmol may also usefully inhibit the VDR. Telmisartan is a strong modulator of PPARgamma (Ki≈0.3 nmol, while Losartan (Ki≈3 nmol, Irbesartan (Ki≈6 nmol, Olmesartan and Valsartan (Ki≈12 nmol also seem likely to have significant PPAR modulatory activity. Olmesartan andIrbesartan (Ki≈9 nmol additionally act as antagonists of a theoretical modelof CCR2b. Initial validation of this CCR2b model was performed, and a proposed model for the AngiotensinII Type1 receptor (AT2R1 has been presented. Conclusion Molecular modeling has proven valuable to generate testable hypotheses concerning receptor/ligand binding and is an important tool in drug design. ARBs were designed to act as antagonists for AT2R1, and it was not surprising to discover their affinity for the structurally similar CCR2b. However, this study also found evidence that ARBs modulate the

  17. Moderation of dietary sodium potentiates the renal and cardiovascular protective effects of angiotensin receptor blockers.

    Science.gov (United States)

    Lambers Heerspink, Hiddo J; Holtkamp, Frank A; Parving, Hans-Henrik; Navis, Gerjan J; Lewis, Julia B; Ritz, Eberhard; de Graeff, Pieter A; de Zeeuw, Dick

    2012-08-01

    Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin-angiotensin-aldosterone system (non-RAASi)-based antihypertensive therapy. Treatment effects on renal and cardiovascular outcomes were compared in subgroups based on dietary sodium intake during treatment, measured as the 24-h urinary sodium/creatinine ratio of 1177 patients with available 24-h urinary sodium measurements. ARB compared to non-RAASi-based therapy produced the greatest long-term effects on renal and cardiovascular events in the lowest tertile of sodium intake. Compared to non-RAASi, the trend in risk for renal events was significantly reduced by 43%, not changed, or increased by 37% for each tertile of increased sodium intake, respectively. The trend for cardiovascular events was significantly reduced by 37%, increased by 2% and 25%, respectively. Thus, treatment effects of ARB compared with non-RAASi-based therapy on renal and cardiovascular outcomes were greater in patients with type 2 diabetic nephropathy with lower than higher dietary sodium intake. This underscores the avoidance of excessive sodium intake, particularly in type 2 diabetic patients receiving ARB therapy.

  18. Effect of Diuretic or Calcium-Channel Blocker Plus Angiotensin-Receptor Blocker on Diastolic Function in Hypertensive Patients.

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    Toh, Norihisa; Ishii, Katsuhisa; Kihara, Hajime; Iwakura, Katsuomi; Watanabe, Hiroyuki; Yoshikawa, Junichi; Ito, Hiroshi

    2016-01-01

    Hypertension increases the risk of left ventricular (LV) diastolic dysfunction, and anti-hypertensive therapy may improve LV relaxation. The aim of this study was to investigate whether combining an angiotensin-receptor blocker (ARB) with either hydrochlorothiazide (HCTZ) or a calcium-channel blocker (CCB) improves LV relaxation in patients with hypertension and diastolic dysfunction. Hypertensive patients who had not achieved their target blood pressure with at least 4 weeks of ARB therapy were randomly assigned to receive either a fixed-dose combination of losartan and HCTZ (losartan/HCTZ; n=110) or a combination of amlodipine and a typical ARB dosage (CCB/ARB; n=121) and followed for 24 weeks. The primary endpoint was change in early diastolic mitral annular velocity (e', cm/s). Systolic blood pressure decreased in both groups after switch to the combination therapies. E' velocity increased both in the losartan/HCTZ (0.52 cm/s) and in the CCB/ARB (0.59 cm/s) groups. The mean (95% CI) treatment difference was -0.02 (-0.37 to 0.34) cm/s, indicating that improvement in LV relaxation was similar between the groups. The ratio of early mitral inflow velocity to e' velocity and left atrial volume index were significantly decreased in the losartan/HCTZ group. The combination of losartan and HCTZ is as effective as amlodipine plus ARB in improving LV relaxation in hypertensive patients.

  19. Long-term use of angiotensin receptor blockers and the risk of cancer.

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    Laurent Azoulay

    Full Text Available The association between angiotensin receptor blockers (ARBs and cancer is controversial with meta-analyses of randomized controlled trials and observational studies reporting conflicting results. Thus, the objective of this study was to determine whether ARBs are associated with an overall increased risk of the four most common cancers, namely, lung, colorectal, breast and prostate cancers, and to explore these effects separately for each cancer type. We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom (UK General Practice Research Database. We assembled a cohort of patients prescribed antihypertensive agents between 1995, the year the first ARB (losartan entered the UK market, and 2008, with follow-up until December 31, 2010. Cases were patients newly-diagnosed with lung, colorectal, breast and prostate cancer during follow-up. We used conditional logistic regression to estimate adjusted rate ratios (RRs and 95% confidence intervals (CIs of cancer incidence, comparing ever use of ARBs with ever use of diuretics and/or beta-blockers. The cohort included 1,165,781 patients, during which 41,059 patients were diagnosed with one of the cancers under study (rate 554/100,000 person-years. When compared to diuretics and/or beta-blockers, ever use of ARBs was not associated with an increased rate of cancer overall (RR: 1.00; 95% CI: 0.96-1.03 or with each cancer site separately. The use of angiotensin-converting enzyme inhibitors and calcium channel blockers was associated with an increased rate of lung cancer (RR: 1.13; 95% CI: 1.06-1.20 and RR: 1.19; 95% CI: 1.12-1.27, respectively. This study provides additional evidence that the use of ARBs does not increase the risk of cancer overall or any of the four major cancer sites. Additional research is needed to further investigate a potentially increased risk of lung cancer with angiotensin-converting enzyme inhibitors and calcium channel blockers.

  20. Calcium channel blockers, more than diuretics, enhance vascular protective effects of angiotensin receptor blockers in salt-loaded hypertensive rats.

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    Eiichiro Yamamoto

    Full Text Available The combination therapy of an angiotensin receptor blocker (ARB with a calcium channel blocker (CCB or with a diuretic is favorably recommended for the treatment of hypertension. However, the difference between these two combination therapies is unclear. The present work was undertaken to examine the possible difference between the two combination therapies in vascular protection. Salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP were divided into 6 groups, and they were orally administered (1 vehicle, (2 olmesartan, an ARB, (3 azelnidipine, a CCB, (4 hydrochlorothiazide, a diuretic, (5 olmesartan combined with azelnidipine, or (6 olmesartan combined with hydrochlorothiazide. Olmesartan combined with either azelnidipine or hydrochlorothiazide ameliorated vascular endothelial dysfunction and remodeling in SHRSP more than did monotherapy with either agent. However, despite a comparable blood pressure lowering effect between the two treatments, azelnidipine enhanced the amelioration of vascular endothelial dysfunction and remodeling by olmesartan to a greater extent than did hydrochlorothiazide in salt-loaded SHRSP. The increased enhancement by azelnidipine of olmesartan-induced vascular protection than by hydrochlorothiazide was associated with a greater amelioration of vascular nicotinamide adenine dinucleotide phosphate (NADPH oxidase activation, superoxide, mitogen-activated protein kinase activation, and with a greater activation of the Akt/endothelial nitric oxide synthase (eNOS pathway. These results provided the first evidence that a CCB potentiates the vascular protective effects of an ARB in salt-sensitive hypertension, compared with a diuretic, and provided a novel rationale explaining the benefit of the combination therapy with an ARB and a CCB.

  1. Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: Effectiveness in combination with diuretics or β-blockers for treating hypertension

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    John D Bisognano

    2007-11-01

    Full Text Available John D Bisognano1, Trent McLaughlin2, Craig S Roberts3, Simon SK Tang31Internal Medicine Department, Cardiology Division, the University of Rochester Medical Center, Rochester, NY, USA; 2NDC Health, Phoenix, Arizona, USA; 3Pfizer Inc, New York, NY, USAAbstract: This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs, angiotensin-converting enzyme (ACE inhibitors, and angiotensin receptor blockers (ARBs added to diuretics or β-blockers. Adults with hypertension treated with diuretic or β-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP ≥140/90 mmHg (≥130/80 mmHg for diabetes mellitus and recorded BP measurements within 6 months before and 1–12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were –17.5/–8.8, –15.7/–6.3, and –13.0/–8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients’ β-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs.Keywords: hypertension, amlodipine besylate, lisinopril, valsartan, Joint National Committee (JNC 6 and 7

  2. Addition of vitamin D reverses the decline in GFR following treatment with ACE inhibitors/angiotensin receptor blockers in patients with chronic kidney disease.

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    Soares, Abel Esteves; Maes, Michael; Godeny, Paula; Matsumoto, Andressa Keiko; Barbosa, Décio Sabbatini; da Silva, Taysa Antonia F; Souza, Flávio Henrique M O; Delfino, Vinicius Daher Alvares

    2017-12-15

    Vitamin D has anti-inflammatory, anti-fibrotic effect, and may block the intrarenal renin-angiotensin system. Adequate vitamin D levels in conjunction with the use of Angiotensin-converting Enzyme Inhibitors/Angiotensin Receptor Blockers may help to slow down chronic kidney disease progression. To study a possible beneficial effect of vitamin D supplementation in chronic kidney disease patients using angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on chronic kidney disease progression we performed a clinical study involving vitamin D supplementation in patients with deficiency of this vitamin. This study was conducted in two chronic kidney disease clinics in the city of Londrina, Brazil, from October 2010 to December 2012. It was involved stage 3 and 4 chronic kidney disease (estimated glomerular filtration rate between 60 and 15mL/min/1.73m 2 ) patients with and without vitamin D deficiency. The patients ingested six-month cholecalciferol 50,000IU oral supplementation to chronic kidney disease patients with vitamin D deficiency. We hypothesize changes in estimated glomerular filtration rate over study period. Our data demonstrate reservation of estimated glomerular filtration with cholecalciferol supplementation to chronic kidney disease patients taking angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. The combination treatment of angiotensin converting enzyme inhibitors/angiotensin receptor blockers with cholecalciferol prevents the decline in estimated glomerular filtration in patients with chronic kidney disease following treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and may represent a valid approach to reduce renal disease progression in chronic kidney disease patients with vitamin D deficiency. This result needs confirmation in prospective controlled clinical trials. Copyright © 2017. Published by Elsevier Inc.

  3. TO STUDY THE EFFECT OF ANGIOTENSIN RECEPTOR BLOCKERS ON DIABETIC RETINOPATHY

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    Chakravarthy K

    2017-05-01

    Full Text Available BACKGROUND Diabetic Retinopathy (DR is the most common microvascular complication of Diabetes Mellitus (DM and is the leading cause of blindness in working age adults of patients with type 1 and 2 DM. Large observational and randomised studies shown that optimal blood glucose and blood pressure control halt or regress the disease and limit the risk of progression to the proliferative stage and visual loss. Recently, evidence has also emerged that Renin-Angiotensin System (RAS inhibitors may electively prevent or delay progression of retinopathy by acting on local RAS. Thus, metabolic and blood pressure control by RAS inhibition is to prevent or limit the onset of retinopathy and its progression towards visual-threatening stages. The aim of the study is to categorise and analyse grading of DR who are on currently ACE and ARBs unchanged for at least 2 years. MATERIALS AND METHODS 178 patients with type 1 and 2 DM of both genders on ARBs and ACEI unchanged for at least 2 years are divided into two groups as follows- 1. ARB group, which includesa 28 patients on losartan (50 mg. b 32 patients on losartan (50 mg + hydrochlorothiazide (12.5 mg. c 28 patients on telmisartan (40 mg. d 32 patients on telmisartan (40 mg + hydrochlorothiazide (12.5 mg. 2. ACE inhibitor group includesa 30 patients on enalapril (5 mg. b 28 patients on ramipril (2.5 mg + hydrochlorothiazide (12.5 mg. Retinopathy grading assessed by indirect ophthalmoscope and comparison of retinopathy grading between ARBs and ACEI groups have done. Two-tailed Chi-square test, GraphPad Prism Software used for statistical calculations. RESULTS Losartan and telmisartan (ARB group showed significant protection from diabetic retinopathy than enalapril and ramipril (ACEI group (p<0.05. CONCLUSION ARBs help in preventing the progression of DR and vision loss in those belonging to mild and moderate nonproliferative diabetic retinopathy patients.

  4. Antihypertensive efficacy of angiotensin receptor blockers in combination with hydrochlorothiazide: a review of the factorial-design studies.

    Science.gov (United States)

    Ram, C Ventika S

    2004-10-01

    Most hypertensive patients require more than one drug for adequate blood pressure (BP) control. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends starting treatment with a thiazide diuretic or, when BP is >20/10 mm Hg above goal or in patients with diabetes, using two different antihypertensive agents. Searches of Medline, EMBASE, and BIOSIS databases identified four similarly designed, randomized, factorial studies comparing various doses of angiotensin II receptor blockers with hydrochlorothiazide as monotherapy and in combination. The methodology and results of these studies were compared. The primary efficacy end point in these studies was a decrease from baseline in mean diastolic BP after 8 weeks of therapy. All currently available angiotensin I receptor blocker/hydrochlorothiazide combinations evaluated (irbesartan, olmesartan medoxomil, telmisartan, and valsartan plus hydrochlorothiazide) produced significant systolic BP and diastolic BP reductions. Olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg provided the largest mean reduction in absolute and placebo-corrected systolic BP/diastolic BP. For all angiotensin II receptor blocker/hydrochlorothiazide combinations evaluated, > or =63% of patients achieved a diastolic BP response (diastolic BP or =10-mm Hg reduction). In conclusion, the combination of an angiotensin II receptor blocker and hydrochlorothiazide produces more substantial BP responses than monotherapy with either component.

  5. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    Directory of Open Access Journals (Sweden)

    Ibrahim F. Benter

    2013-01-01

    Full Text Available Aims. We evaluated the effects of RU28318 (RU, a selective mineralocorticoid receptor (MR antagonist, Captopril (Capt, an angiotensin converting enzyme inhibitor, and Losartan (Los, an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R- induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I followed by a period of 30 min of reperfusion (R. Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple. Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving -dP/dt (a measure of diastolic function when administered to diabetic hearts after ischemia.

  6. Associations between ACE-Inhibitors, Angiotensin Receptor Blockers, and Lean Body Mass in Community Dwelling Older Women

    Directory of Open Access Journals (Sweden)

    Jennifer W. Bea

    2018-01-01

    Full Text Available Studies suggest that ACE-inhibitors (ACE-I and angiotensin receptor blockers (ARBs may preserve skeletal muscle with aging. We evaluated longitudinal differences in lean body mass (LBM among women diagnosed with hypertension and classified as ACE-I/ARB users and nonusers among Women’s Health Initiative participants that received dual energy X-ray absorptiometry scans to estimate body composition (n=10,635 at baseline and at years 3 and 6 of follow-up. Of those, 2642 were treated for hypertension at baseline. Multivariate linear regression models, adjusted for relevant demographics, behaviors, and medications, assessed ACE-I/ARB use/nonuse and LBM associations at baseline, as well as change in LBM over 3 and 6 years. Although BMI did not differ by ACE-I/ARB use, LBM (% was significantly higher in ACE-I/ARB users versus nonusers at baseline (52.2% versus 51.3%, resp., p=0.001. There was no association between ACE-I/ARB usage and change in LBM over time. Reasons for higher LBM with ACE-I/ARB use cross sectionally, but not longitundinally, are unclear and may reflect a threshold effect of these medications on LBM that is attenuated over time. Nevertheless, ACE-I/ARB use does not appear to negatively impact LBM in the long term.

  7. Cognitive enhancing effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on learning and memory

    Science.gov (United States)

    Nade, V. S.; Kawale, L. A.; Valte, K. D.; Shendye, N. V.

    2015-01-01

    Objective: The present study was designed to investigate cognitive enhancing property of angiotensin-converting enzymes inhibitors (ACEI) and angiotensin receptor blockers (ARBs) in rats. Materials and Methods: The elevated plus maze (EPM), passive avoidance test (PAT), and water maze test (WMT) were used to assess cognitive enhancing activity in young and aged rats. Ramipril (10 mg/kg, p.o.), perindopril (10 mg/kg, i.p), losartan (20 mg/kg, i.p), and valsartan (20 mg/kg, p.o) were administered to assess their effect on learning and memory. Scopolamine (1 mg/kg, i.p) was used to impair cognitive function. Piracetam (200 mg/kg, i.p) was used as reference drug. Results: All the treatments significantly attenuated amnesia induced by aging and scopolamine. In EPM, aged and scopolamine-treated rats showed an increase in transfer latency (TL) whereas, ACEI and ARBs showed a significant decrease in TL. Treatment with ACEI and ARBs significantly increased step down latencies and decreased latency to reach the platform in target quadrant in young, aged and scopolamine-treated animals in PAT and WMT, respectively. The treatments inhibited acetylcholinesterase (AChE) enzyme in the brain. Similarly, all the treatments attenuated scopolamine-induced lipid peroxidation and normalize antioxidant enzymes. Conclusion: The results suggest that the cognitive enhancing effect of ACEI and ARBs may be due to inhibition of AChE or by regulation of antioxidant system or increase in formation of angiotensin IV. PMID:26069362

  8. Treatment of angiotensin receptor blocker-induced angioedema: A case series.

    Science.gov (United States)

    Strassen, Ulrich; Bas, Murat; Hoffmann, Thomas K; Knopf, Andreas; Greve, Jens

    2015-07-01

    Angiotensin II receptor antagonists have been proposed as a replacement therapy after the occurrence of either an angiotensin converting enzyme (ACE) inhibitor-induced angioedema or cough. However, recent studies indicate that angioedema is associated with elevated bradykinin levels in a small fraction of patients treated with angiotensin-II-receptor blockers, suggesting a common pathophysiological mechanism. To date, a standard treatment for angiotensin II receptor blocker-induced angioedema does not exist. We present a case series of patients admitted to our hospital due to angioedema induced by an angiotensin II receptor blocker. The patients were either treated with either icatibant (n = 3) or prednisolone-21-hydrogen succinate/clemastine (n = 5). Both patient groups were compared with an untreated patient cohort (n = 3). All patients were previously diagnosed with essential hypertonia. Icatibant was an effective therapy for angiotensin II receptor blocker-induced angioedema. Full symptom recovery was achieved after 5 to 7 hours, whereas symptom remission occurred within 27 to 52 and 24 to 54 hours in patients treated with Solu-Decortin prednisolone/clemastine and untreated patients, respectively. The recovery time for icatibant was similar to that described in previous studies regarding the therapeutic efficacy of icatibant for the treatment of hereditary angioedema and patients suffering from angiotensin converting enzyme inhibitor-induced angioedema. Icatibant is a safe and effective substance for the treatment of angiotensin II receptor blocker-induced angioedema. Although the pathophysiology of angiotensin II receptor blocker-induced angioedema remains unclear, it appears to be associated with the bradykinin pathway. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Trends in co-prescribing of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in Ireland.

    LENUS (Irish Health Repository)

    Wan Md Adnan, Wan A H

    2011-03-01

    (i) To examine the trends in co-prescribing of angiotensin converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) therapy and (ii) to examine the influence of major clinical trials (CALM, COOPERATE, VALIANT and ONTARGET) on co-prescribing.

  10. Differential blood pressure reductions by angiotensin receptor blocker plus calcium channel blocker or diuretic in elderly hypertension with or without obesity.

    Science.gov (United States)

    Kato, Johji; Yokota, Naoto; Tamaki, Noboru; Kariya, Sumito; Kita, Toshihiro; Ayabe, Takao; Eto, Tanenao; Kitamura, Kazuo

    2012-01-01

    We conducted the Miyazaki Olmesartan Therapy for Hypertension in the EldeRly (MOTHER) study, which suggested that there are preferable effects of an angiotensin receptor blocker (ARB), olmesartan, plus a calcium channel blocker (CCB) over the ARB plus a diuretic, in elderly patients with hypertension. In this subanalysis, we examined whether obesity influences the efficacies of these combination therapies. The study subjects were 58 hypertensive patients ages 65 to 85, who had been randomly assigned to either group treated with olmesartan plus a CCB or a diuretic and completed the treatment for 6 months. Systolic and diastolic blood pressures were reduced following these combination treatments in nonobese and obese patients. In the CCB combination, blood pressure reductions in nonobese patients were larger than in obese patients at 1 and 3 months, and serum creatinine remained unchanged despite the greater reduction of blood pressure. Meanwhile, such differences were not noted in the diuretic groups. Plasma aldosterone was significantly reduced in nonobese patients of two combination groups, but not in those with obesity. ARB plus CCB combination therapy might be preferably chosen for nonobese elderly patients, whereas the influence of obesity seems smaller in the efficacy of ARB plus a diuretic. Copyright © 2012 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  11. Efficacy and safety of telmisartan monotherapy in the black ...

    African Journals Online (AJOL)

    The use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in addition to control of blood pressure delays the development of end organ damage associated with hypertension. This study was undertaken to investigate the efficacy and safety of telmisartan as monotherapy in Nigerian black ...

  12. Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the management of atrial fibrillation.

    Science.gov (United States)

    Anis, Rafik R

    2009-01-01

    Atrial fibrillation (AF) is the most common clinical arrhythmia, and is difficult to treat. Current treatment strategies are far from optimal. Antiarrhythmic drug therapy to maintain sinus rhythm is limited by inadequate efficacy and potentially serious side effects. New areas of research include targeting the AF substrate and examining whether drugs can produce atrial structural and/or electrophysiological remodelling, and whether this results in a reduction in AF burden. There are two approaches to the treatment of AF. The first approach is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm. The other approach is the use of rate-controlling drugs allowing AF to persist. In both approaches, the use of anticoagulant drugs is recommended. There is an increasing interest in novel therapeutic approaches that target AF-substrate development. Recent trials suggest that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor II blockers (ARBs) may be useful, particularly in patients with left ventricular hypertrophy, hypertension, chronic heart failure and left ventricular dysfunction. While experimental studies have shown that the pathogenic structural and electrical remodelling of the atria are prevented by inhibition of angiotensin II, the clinical potential and mechanisms of this approach are still under active investigation. The present article will discuss information pertaining to the mechanism of action and clinical use of ACEIs and ARBs in AF. It will also review the current data on the use of ACEIs and ARBs in a high-risk group of AF patients (heart failure, hypertensive with left ventricular hypertrophy, and myocardial infarction), together with the potential benefit of this class type of pharmacological therapy in direct current cardioversion and after radiofrequency catheter ablation.

  13. Individual long-term albuminuria exposure during angiotensin receptor blocker therapy is the optimal predictor for renal outcome.

    Science.gov (United States)

    Felix Kröpelin, Tobias; de Zeeuw, Dick; Holtkamp, Frank Arjan; Packham, David Kenneth; L Heerspink, Hiddo J

    2016-09-01

    Albuminuria reduction due to angiotensin receptor blockers (ARBs) predicts subsequent renoprotection. Relating the initial albuminuria reduction to subsequent renoprotection assumes that the initial ARB-induced albuminuria reduction remains stable during follow-up. The aim of this study was to assess individual albuminuria fluctuations after the initial ARB response and to determine whether taking individual albuminuria fluctuations into account improves renal outcome prediction. Patients with diabetes and nephropathy treated with losartan or irbesartan in the RENAAL and IDNT trials were included. Patients with >30% reduction in albuminuria 3 months after ARB initiation were stratified by the subsequent change in albuminuria until Month 12 in enhanced responders (>50% albuminuria reduction), sustained responders (between 20 and 50% reduction), and response escapers (albuminuria exposure until Month 3 was compared with the exposure over the first 12 months using receiver operating characteristics (ROC) curves. Following ARB initiation, 388 (36.3%) patients showed an >30% reduction in albuminuria. Among these patients, the albuminuria level further decreased in 174 (44.8%), remained stable in 123 (31.7%), and increased in 91 (23.5%) patients. Similar albuminuria fluctuations were observed in patients with albuminuria reduction. Renal risk prediction improved when using the albuminuria exposure during the first 12 months versus the initial Month 3 change [ROC difference: 0.78 (95% CI 0.75-0.82) versus 0.68 (0.64-0.72); P albuminuria variability is observed. Hence, incorporating multiple albuminuria measurements over time in risk algorithms may be more appropriate to monitor treatment effects and quantify renal risk. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  14. The importance of short-term off-target effects in estimating the long-term renal and cardiovascular protection of angiotensin receptor blockers

    DEFF Research Database (Denmark)

    Smink, P A; Miao, Y; Eijkemans, M J C

    2014-01-01

    Angiotensin receptor blockers (ARBs) have multiple effects that may contribute to their efficacy on renal/cardiovascular outcomes. We developed and validated a risk score that incorporated short-term changes in multiple risk markers to predict the ARB effect on renal/cardiovascular outcomes.......98), in addition to being markedly more accurate than predicted RRRs based on changes in single markers. The score was validated in an independent ARB trial. Predictions of long-term renal/cardiovascular ARB effects are more accurate when considering short-term changes in multiple risk markers, challenging the use...

  15. Renin-angiotensin-aldosterone system inhibition: overview of the therapeutic use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and direct renin inhibitors.

    Science.gov (United States)

    Mercier, Kelly; Smith, Holly; Biederman, Jason

    2014-12-01

    Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy in hypertensive diabetic patients with macroalbuminuria, microalbuminuria, or normoalbuminuria has been repeatedly shown to improve cardiovascular mortality and reduce the decline in glomerular filtration rate. Renin-angiotensin-aldosterone system (RAAS) blockade in normotensive diabetic patients with normoalbuminuria or microalbuminuria cannot be advocated at present. Dual RAAS inhibition with ACE inhibitors plus ARBs or ACE inhibitors plus direct renin inhibitors has failed to improve cardiovascular or renal outcomes but has predisposed patients to serious adverse events. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. A comparative study of the prevalence of hyperkalemia with the use of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers

    Directory of Open Access Journals (Sweden)

    Seyed Ali Sadjadi

    2009-07-01

    Full Text Available Seyed Ali Sadjadi1, James I McMillan1, Navin Jaipaul1, Patricia Blakely1, Su Su Hline21Section of Nephrology (111N, Jerry L Pettis Memorial Veterans Medical Center, Loma Linda, CA, USA; 2Divison of Nephrology, Loma Linda University Medical Center, Loma Linda, CA, USABackground and objectives: Angiotensin-converting enzyme inhibitors (ACEI and angiotensin receptor blockers (ARB are increasingly used in a variety of settings including heart failure, renal failure, arterial hypertension, and diabetic nephropathy. The objective of this study was to investigate the prevalence of hyperkalemia with ACEI and ARB use, in a population of the United States veterans.Design, settings, material, and measurements: Retrospective observational cohort study of 1163 patients on ACEIs and 1168 patients on ARBs in a single Veterans Affairs Medical Center. Electronic medical records were reviewed over a 12-month period with data collected on various demographic, laboratory, comorbidity, and medication related variables. Results: Hyperkalemia (>5 mEq/L was observed in 20.4% of patients on ACEIs and 31.0% on ARBs. Severe hyperkalemia (6 mEq/L or higher, was observed in 0.8% of ACEI and 2.8% of ARB users. In univariate logistic regression analyses, diabetes mellitus; serum glucose, total carbon dioxide content, creatinine, and estimated glomerular filtration rate (GFR were significantly associated with hyperkalemia. ARB use, when compared to ACEI, was associated with a 42% increase in odds of hyperkalemia (odds ratio [OR] = 1.42; p = 0.001 in a model including adjustment for GFR and a 56% increase in odds of hyperkalemia (OR = 1.56; p < 0.001 in a model including adjustment for serum creatinine.Conclusions: Hyperkalemia, associated with the use of ACEIs and ARBs, is usually mild and severe hyperkalemia is rare. Hyperkalemia is more common with ARBs than ACEIs. ARB use, when compared to ACEI use, may significantly and independently be associated with increased odds of

  17. Treatment of primary chronic glomerulonephritis with Rehmannia glutinosa acteosides in combination with the angiotensin receptor blocker irbesartan: a randomized controlled trial.

    Science.gov (United States)

    Qiu, HongYu; Fu, Ping; Fan, WenXing; Zuo, Chuan; Feng, Ping; Shi, Peng; Cao, Lina; Liu, Fang; Zhou, Li; Chen, Feng; Zhong, Hui; Gou, ZhongPing; Liang, YaPing; Shi, Mei

    2014-01-01

    This study aims to assess the efficacy and safety of Rehmannia glutinosa acteosides used in combination with the angiotensin receptor blocker irbesartan to treat primary chronic glomerulonephritis. A total of 479 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (Rehmannia glutinosa acteosides, two 200-mg capsules, bid; and irbesartan, one 150-mg tablet, qd) or the control group (irbesartan, one 150-mg tablet, qd). The primary outcome was 24-h urinary protein. Secondary outcome measures included blood pressure, estimated glomerular filtration rate, erythrocyturia, serum alanine aminotransferase, aspartate transaminase and electrolytes. After 8 weeks of treatment, the treatment group showed a mean reduction in 24-h proteinuria of 36.42% compared to baseline, which was significantly higher than the mean reduction from baseline of 27.97% in the control group (P = 0.0278).Adverse drug reactions occurred at a similarly low rate in the treatment group (0.4%) and control group (1.2%, P = 0.3724). In the treatment of chronic glomerulonephritis, the combination of Rehmannia glutinosa acteosides and irbesartan can reduce proteinuria more effectively than irbesartan alone. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial.

    Science.gov (United States)

    Uzu, Takashi; Araki, Shin-Ichi; Kashiwagi, Atsunori; Haneda, Masakazu; Koya, Daisuke; Yokoyama, Hiroki; Kida, Yasuo; Ikebuchi, Motoyoshi; Nakamura, Takaaki; Nishimura, Masataka; Takahara, Noriko; Obata, Toshiyuki; Omichi, Nobuyuki; Sakamoto, Katsuhiko; Shingu, Ryosuke; Taki, Hideki; Nagai, Yoshio; Tokuda, Hiroaki; Kitada, Munehiro; Misawa, Miwa; Nishiyama, Akira; Kobori, Hiroyuki; Maegawa, Hiroshi

    2016-01-01

    In patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity. We randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to albuminuria. Twelve patients dropped out during the observation period, and a total of 225 patients were analyzed. During the study period, the systolic and diastolic blood pressures were not different between the groups. The changes in the urinary albumin-to-creatinine ratio from baseline to the end of the treatment period in the DRI and ARB groups were similar (-5.5% and -6.7%, respectively). In contrast, a significant reduction in the urinary excretion of angiotensinogen was observed in the ARB group but not in the DRI group. In the subgroup analysis, a significant reduction in the albuminuria was observed in the ARB group but not in the DRI group among high-normal albuminuria patients. DRI and ARB reduced albuminuria in hypertensive patients with type 2 diabetes. In addition, ARB, but not DRI, reduced albuminuria even in patients with normal albuminuria. DRI is not superior to ARB in the reduction of urinary excretion of albumin and angiotensinogen.

  19. The effect of angiotensin receptor blockers on C-reactive protein and other circulating inflammatory indices in man

    Science.gov (United States)

    Alessandra, Del Fiorentino; Cianchetti, Silvana; Celi, Alessandro; Dell’Omo, Giulia; Pedrinelli, Roberto

    2009-01-01

    Anti-inflammatory properties may contribute to the pharmacological effects of angiotensin II receptor blockers (ARBs), a leading therapeutic class in the management of hypertension and related cardiovascular and renal diseases. That possibility, supported by consistent evidence from in-vitro and animal studies showing pro-inflammatory properties of angiotensin II, has been evaluated clinically by measuring the effect of ARBs on C-reactive protein and other circulating indices of inflammation (e-selectin, adhesion molecules, interleukin-6, tissue necrosis factor-alpha, monocyte chemoattractant protein-1) of potential clinical relevance, a body of evidence that this paper aims to review. PMID:19436669

  20. Association between exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prior to septic shock and acute kidney injury.

    Science.gov (United States)

    Suberviola, B; Rodrigo, E; González-Castro, A; Serrano, M; Heras, M; Castellanos-Ortega, Á

    To evaluate the association between angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use prior to a septic shock episode and the development, prognosis and long-term recovery from acute kidney injury (AKI). A single-centre, prospective observational study was carried out between September 2005 and August 2010. Patients admitted to the ICU of a third level hospital. A total of 386 septic shock patients were studied. None. Use of ACEIs/ARBs, AKI development, recovery of previous creatinine levels and time to recovery. A total of 386 patients were included, of which 312 (80.8%) developed AKI during ICU stay and 23% were receiving ACEIs/ARBs. The percentage of patients on ACEIs/ARBs increased significantly in relation to more severe stages of AKI irrespective of the kind of AKI score. After adjusting for confounders, the development of AKI was independently associated to the use of ACEIs/ARBs (OR 2.19; 95%CI 1.21-3.84; p=.04). With respect to the recovery of kidney function, the group of patients on ACEIs/ARBs had significantly higher creatinine levels at ICU discharge and needed hemodialysis more frequently thereafter. However, use of ACEIs/ARBs affected neither recovery of previous creatinine levels nor significantly delayed recovery. The use of ACEIs/ARBs before septic shock episodes was correlated to AKI development and severity, but did not affect the recovery of kidney function after sepsis resolution. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  1. Mortality benefit of long-term angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after successful percutaneous coronary intervention in non-ST elevation acute myocardial infarction.

    Science.gov (United States)

    González-Cambeiro, María Cristina; López-López, Andrea; Abu-Assi, Emad; Raposeiras-Roubín, Sergio; Peña-Gil, Carlos; García-Acuña, José; González-Juanatey, Ramón

    2016-12-01

    Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to reduce mortality after myocardial infarction (MI). Current guidelines recommend their prescription in all patients after MI. Limited data are available on whether ACEIs/ARBs still improve prognosis in the contemporary era of non-ST elevation MI (NSTEMI) management. We aimed to evaluate the mortality benefit of ACEIs/ARBs in NSTEMI patients treated successfully with percutaneous coronary intervention (PCI). We analyzed 2784 patients with NSTEMI treated successfully with in-hospital PCI. Two groups were formed based on ACEI/ARB prescription at discharge. Two propensity score (PS) analyses were performed to control for differences in covariates: one with adjustment among the entire cohort, and the other with PS matching (n=1626). The outcome variable was all-cause mortality at four-year follow-up. There were 1902 (68.3%) patients prescribed ACEIs/ARBs at discharge. When adjusted by PS, ACEI/ARB use was associated with a hazard ratio (HR) for mortality of 0.75 (0.60-0.94; absolute risk reduction [ARR] 4.0%) in the whole cohort (p=0.01). After one-to-one PS matching (n=813 in each group), the mortality rate was significantly lower in patients prescribed ACEIs/ARBs, with HR of 0.77 (0.63-0.94; ARR 3.8%) (p=0.03). In this observational study of patients with NSTEMI, all of them treated successfully by PCI, the use of ACEIs/ARBs was significantly associated with a lower risk of four-year all-cause mortality. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Addition of hydrochlorothiazide to angiotensin receptor blocker therapy can achieve a lower sodium balance with no acceleration of intrarenal renin angiotensin system in patients with chronic kidney disease.

    Science.gov (United States)

    Fuwa, Daisuke; Fukuda, Michio; Ogiyama, Yoshiaki; Sato, Ryo; Mizuno, Masashi; Miura, Toshiyuki; Abe-Dohmae, Sumiko; Michikawa, Makoto; Kobori, Hiroyuki; Ohte, Nobuyuki

    2016-01-01

    Angiotensin receptor blockers (ARBs) produce a lower sodium (Na) balance, and the natriuretic effect is enhanced under Na deprivation, despite falls in blood pressure (BP) and glomerular filtration rate (GFR). The effect of additional hydrochlorothiazide (HCTZ; 12.5 mg/day) to ARB treatment (valsartan; 80 mg/day) on glomerulotubular Na balance was evaluated in 23 patients with chronic kidney disease. Add-on HCTZ decreased GFR, tubular Na load, and tubular Na reabsorption (t(Na)), although 24-hour urinary Na excretion (U(Na)V) remained constant. Daily urinary angiotensinogen excretion (U(AGT)V, 152±10→82±17 μg/g Cre) reduced (p=0.02). Changes in tubular Na load (r(2)=0.26) and t(Na) (r(2)=0.25) correlated with baseline 24-hour U(AGT)V. Changes in filtered Na load correlated with changes in nighttime systolic BP (r(2)=0.17), but not with changes in daytime systolic BP. The change in the t(Na) to filtered Na load ratio was influenced by the change in daytime U(Na)V (β=-0.67, F=16.8), rather than the change in nighttime U(Na)V. Lower Na balance was produced by add-on HCTZ to ARB treatment without an increase of intra-renal renin-angiotensin system activity, leading to restoration of nocturnal hypertension. A further study is needed to demonstrate that the reduction of U(AGT)V by additional diuretics to ARBs prevents the progression of nephropathy or cardiovascular events. © The Author(s) 2016.

  3. An initial reduction in serum uric acid during angiotensin receptor blocker treatment is associated with cardiovascular protection: a post-hoc analysis of the RENAAL and IDNT trials.

    Science.gov (United States)

    Smink, Paul A; Bakker, Stephan J L; Laverman, Gozewijn D; Berl, Tomas; Cooper, Mark E; de Zeeuw, Dick; Lambers Heerspink, Hiddo J

    2012-05-01

    Increased levels of serum uric acid (SUA) are thought to be an independent risk marker for cardiovascular complications. Treatment with the angiotensin receptor blocker (ARB) losartan lowers SUA in contrast to other ARBs. Whether reductions in SUA during ARB therapy are associated with cardiovascular protection is unclear. We aimed to investigate this. In a post-hoc analysis of the Reduction of Endpoints in Non insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan Diabetic Nephropathy (IDNT) trials we determined whether the short-term effect of losartan and of irbesartan on SUA is related with long-term cardiovascular outcome by means of Cox regression. Compared to placebo, losartan significantly changed SUA [-0.16  mg/dl; 95% confidence interval (CI) -0.01 to -0.30; P = 0.031], whereas irbesartan did not (-0.09  mg/dl; (95% CI 0.09 to -0.28; P = 0.30). Each 0.5  mg/dl decrement in SUA during losartan treatment in the first 6 months resulted in a reduction in the risk of cardiovascular outcomes by 5.3% (95% CI 0.9 to 9.9; P = 0.017). Losartan reduced the risk of cardiovascular outcomes by 9.2% (95% CI -7.9 to 23.6). Adjustment for the 6-month change in SUA attenuated the treatment effect to 4.6% (95% CI -16.2 to 22.0), suggesting that part of the cardiovascular protective effect of losartan is attributable to its short-term effect on SUA. Losartan but not irbesartan significantly lowers SUA compared to placebo in patients with type 2 diabetes and nephropathy. The degree of reduction in SUA explains part of the cardiovascular effect of losartan. This supports the hypothesis that SUA is a modifiable risk factor for cardiovascular disease, at least in type 2 diabetics with nephropathy.

  4. Telmisartan to prevent recurrent stroke and cardiovascular events

    DEFF Research Database (Denmark)

    Yusuf, Salim; Diener, Hans-Christoph; Sacco, Ralph L

    2008-01-01

    pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. METHODS: In a multicenter trial involving 20,332 patients who recently had...... an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening...... heart failure) and new-onset diabetes. RESULTS: The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group...

  5. Beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine, diuretics, aldosterone antagonist, ivabradine, devices and digoxin (BANDAID(2) ): an evidence-based mnemonic for the treatment of systolic heart failure.

    Science.gov (United States)

    Chia, N; Fulcher, J; Keech, A

    2016-06-01

    Heart failure causes significant morbidity and mortality, with recognised underutilisation rates of guideline-based therapies. Our aim was to review current evidence for heart failure treatments and derive a mnemonic summarising best practice, which might assist physicians in patient care. Treatments were identified for review from multinational society guidelines and recent randomised trials, with a primary aim of examining their effects in systolic heart failure patients on mortality, hospitalisation rates and symptoms. Secondary aims were to consider other clinical benefits. MEDLINE and EMBASE were searched using a structured keyword strategy and the retrieved articles were evaluated methodically to produce an optimised reference list for each treatment. We devised the mnemonic BANDAID (2) , standing for beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine (or potentially neprilysin inhibitor), diuretics, aldosterone antagonist, ivabradine, devices (automatic implantable cardioverter defibrillator, cardiac resynchronisation therapy or both) and digoxin as a representation of treatments with strong evidence for their use in systolic heart failure. Treatment with omega-3 fatty acids, statins or anti-thrombotic therapies has limited benefits in a general heart failure population. Adoption of this mnemonic for current evidence-based treatments for heart failure may help improve prescribing rates and patient outcomes in this debilitating, high mortality condition. © 2016 Royal Australasian College of Physicians.

  6. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study.

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    Lapi, Francesco; Azoulay, Laurent; Yin, Hui; Nessim, Sharon J; Suissa, Samy

    2013-01-08

    To assess whether a double therapy combination consisting of diuretics, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers with addition of non-steroidal anti-inflammatory drugs (NSAIDs) and the triple therapy combination of two of the aforementioned antihypertensive drugs to which NSAIDs are added are associated with an increased risk of acute kidney injury. Retrospective cohort study using nested case-control analysis. General practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. A cohort of 487,372 users of antihypertensive drugs. Rate ratios with 95% confidence intervals of acute kidney injury associated with current use of double and triple therapy combinations of antihypertensive drugs with NSAIDs. During a mean follow-up of 5.9 (SD 3.4) years, 2215 cases of acute kidney injury were identified (incidence rate 7/10,000 person years). Overall, current use of a double therapy combination containing either diuretics or angiotensin converting enzyme inhibitors or angiotensin receptor blockers with NSAIDs was not associated with an increased rate of acute kidney injury. In contrast, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio 1.31, 95% confidence interval 1.12 to 1.53). In secondary analyses, the highest risk was observed in the first 30 days of use (rate ratio 1.82, 1.35 to 2.46). A triple therapy combination consisting of diuretics with angiotensin converting enzyme inhibitors or angiotensin receptor blockers and NSAIDs was associated with an increased risk of acute kidney injury. The risk was greatest at the start of treatment. Although antihypertensive drugs have cardiovascular benefits, vigilance may be warranted when they are used concurrently with NSAIDs.

  7. Melanoma and Non-Melanoma Skin Cancer Associated with Angiotensin-Converting-Enzyme Inhibitors, Angiotensin-Receptor Blockers and Thiazides: A Matched Cohort Study.

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    Nardone, Beatrice; Majewski, Sara; Kim, Ashley S; Kiguradze, Tina; Martinez-Escala, Estela M; Friedland, Rivka; Amin, Ahmad; Laumann, Anne E; Edwards, Beatrice J; Rademaker, Alfred W; Martini, Mary C; West, Dennis P

    2017-03-01

    Controversy exists about an association between angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), and thiazides (TZs) and the risk of malignant melanoma (MM), and non-melanoma skin cancer-basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The aim of this study was to determine if an association exists for ACEI, ARB, or TZ exposure and skin cancers. This was a matched cohort study using a large electronic medical records repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW). The exposed population consisted of patients with a documented order for an ACEI, ARB, or TZ with no prior history of skin cancer. The control population consisted of matched patients without documented exposure to ACEI, ARB, or TZ and no previous skin cancer. Incident MM, BCC, or SCC diagnosis by ICD-9 codes was recorded. Odds ratios (ORs) were obtained by using logistic regression analyses. Among the 27,134 patients exposed to an ACEI, 87 MM, 533 BCC, and 182 SCC were detected. Among the 13,818 patients exposed to an ARB, 96 MM, 283 BCC, and 106 SCC were detected. Among the 15,166 patients exposed to a TZ, 99 MM, 262 BCC, and 130 SCC were detected. Significant associations using ORs from logistic regression were found for MM and TZs (OR 1.82; 95% confidence interval [CI] 1.01-3.82); BCC and ARBs (OR 2.86; 95% CI 2.13-3.83), ACEIs (OR 2.23; 95% CI 1.78-2.81) and TZs (OR 2.11; 95% CI 1.60-2.79); SCC and ARBs (OR 2.22; 95% CI 1.37-3.61), ACEIs (OR 1.94; 95% CI 1.37-2.76), and TZs (OR 4.11; 95% CI 2.66-6.35). A safety signal for ACEIs, ARBs, and TZs and BCC and SCC, as well as for TZs and MM, was detected. An increased awareness and education, especially for those who are at high risk for skin cancer, are warranted for patients and healthcare providers. Further exploration of such associations for these commonly used drug classes is warranted.

  8. Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan

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    Huang Shiou-Huei

    2012-05-01

    Full Text Available Abstract Background A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs] to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. Methods Using the Taiwan’s Longitudinal Health Insurance Database (2005, we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. Results The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088 and in ARBs after price adjustments in 2001 (173.4%, p  Conclusions Price adjustments did not achieve long-term cost savings for overall renin-angiotensin drugs. Possible switching from ACEIs to ARBs

  9. Telmisartan protects against diabetic vascular complications in a mouse model of obesity and type 2 diabetes, partially through peroxisome proliferator activated receptor-{gamma}-dependent activity

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Kensuke; Nakamura, Taishi; Kataoka, Keiichiro [Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto (Japan); Yasuda, Osamu [Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital, Kumamoto (Japan); Fukuda, Masaya; Tokutomi, Yoshiko; Dong, Yi-Fei [Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto (Japan); Ogawa, Hisao [Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto (Japan); Kim-Mitsuyama, Shokei, E-mail: kimmitsu@gpo.kumamoto-u.ac.jp [Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto (Japan)

    2011-07-08

    Highlights: {yields} Telmisartan, an angiotensin receptor blocker, acts as a partial PPAR{gamma} agonist. {yields} The protective effects of telmisartan against diabetic vascular injury were associated with attenuation of vascular NF{kappa}B activation and TNF {alpha}. {yields} PPAR{gamma} activity of telmisartan was involved in the normalization of vascular PPAR{gamma} downregulation in diabetic mice. {yields} We provided the first evidence indicating that PPAR{gamma} activity of telmisartan contributed to the protective effects of telmisartan against diabetic vascular complication. -- Abstract: Experimental and clinical data support the notion that peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) activation is associated with anti-atherosclerosis as well as anti-diabetic effect. Telmisartan, an angiotensin receptor blocker (ARB), acts as a partial PPAR{gamma} agonist. We hypothesized that telmisartan protects against diabetic vascular complications, through PPAR{gamma} activation. We compared the effects of telmisartan, telmisartan combined with GW9662 (a PPAR{gamma} antagonist), and losartan with no PPAR{gamma} activity on vascular injury in obese type 2 diabetic db/db mice. Compared to losartan, telmisartan significantly ameliorated vascular endothelial dysfunction, downregulation of phospho-eNOS, and coronary arterial remodeling in db/db mice. More vascular protective effects of telmisartan than losartan were associated with greater anti-inflammatory effects of telmisartan, as shown by attenuation of vascular nuclear factor kappa B (NF{kappa}B) activation and tumor necrosis factor {alpha}. Coadministration of GW9662 with telmisartan abolished the above mentioned greater protective effects of telmisartan against vascular injury than losartan in db/db mice. Thus, PPAR{gamma} activity appears to be involved in the vascular protective effects of telmisartan in db/db mice. Moreover, telmisartan, but not losartan, prevented the downregulation of

  10. A meta-analysis of the effect of angiotensin receptor blockers and calcium channel blockers on blood pressure, glycemia and the HOMA-IR index in non-diabetic patients.

    Science.gov (United States)

    Yang, Yue; Wei, Ri-bao; Xing, Yue; Tang, Lu; Zheng, Xiao-yong; Wang, Zi-cheng; Gao, Yu-wei; Li, Min-xia; Chen, Xiang-mei

    2013-12-01

    This study compared the efficacy of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) in the effect of insulin resistance (IR) as assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) in non-diabetic patients. The MEDLINE, EMBASE, and Cochrane Library databases were searched to identify studies published before December 2012 that investigated the use of ARBs and CCBs to determine the effect on the HOMA-IR index in non-diabetics. Parameters on IR and blood pressure were collected. Review Manager 5.2 and Stata 12.0 were used to perform the meta-analysis. Fixed and random effects models were applied to various aspects of the meta-analysis, which assessed the therapeutic effects of the two types of drug using the HOMA-IR index in non-diabetic patients. The meta-analysis included five clinical trials. Patient comparisons before and after treatment with ARBs and CCBs revealed that ARBs reduced the HOMA-IR index (weighted mean difference (WMD) -0.65, 95% confidence interval (CI) -0.93 to -0.38) and fasting plasma insulin (FPI) (WMD -2.01, 95% CI -3.27 to -0.74) significantly more than CCBs. No significant differences in the therapeutic effects of these two types of drug on blood pressure were observed. Given that there are no significant differences in the therapeutic effects of ARBs and CCBs on blood pressure, as ARBs are superior to CCBs in their effect on the HOMA-IR index in non-diabetics, they might be a better choice in hypertension patients without diabetes. © 2013.

  11. Skin cancer associated with commonly prescribed drugs: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and statins -weighing the evidence.

    Science.gov (United States)

    Nardone, Beatrice; Orrell, Kelsey A; Vakharia, Paras P; West, Dennis P

    2018-02-01

    Skin cancers, including both malignant melanoma (MM) and nonmelanoma skin cancer (NMSC), are the most commonly diagnosed cancers in the US. The incidence of both MM and NMSC continues to rise. Areas covered: Current evidence for an association between four of the most commonly prescribed classes of drugs in the U.S. and risk for MM and NMSC is reported. Medline was searched (January 2000 to May 2017) for each drug in the classes and for 'basal cell carcinoma', 'squamous cell carcinoma', 'non-melanoma skin cancer', 'skin cancer' and 'melanoma'. Skin cancer risk information was reported for: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (statins). Expert opinion: Since skin cancer risk is associated with all four classes of these commonly prescribed drugs that represent nearly 20% of the Top 100 drugs in the U.S., these important findings warrant enhanced education, especially for prescribers and those patients at high risk for skin cancer.

  12. Risk of hyperkalemia and combined use of spironolactone and long-term ACE inhibitor/angiotensin receptor blocker therapy in heart failure using real-life data: a population- and insurance-based cohort.

    Science.gov (United States)

    Abbas, Sascha; Ihle, Peter; Harder, Sebastian; Schubert, Ingrid

    2015-04-01

    Clinical trials and few observational studies report increased hyperkalemia risks in heart failure patients receiving aldosterone blockers in addition to standard therapy. The aim of this study is to assess the hyperkalemia risk and combined use of spironolactone and long-term ACE (angiotensin-converting enzyme) inhibitor/angiotensin receptor blocker (ARB) therapy for heart failure in a real-life setting of a heterogeneous population. Using claims data of the statutory health insurance fund AOK, covering 30% of the German population, we performed a nested case-control study in a cohort of heart failure patients receiving continuous ACE/ARB therapy (n = 1,491,894). Hyperkalemia risk associated with concurrent use of spironolactone and ACE/ARB was calculated by conditional logistic regression in 1062 cases and 10,620 risk-set-sampling-matched controls. Risk of hyperkalemia in heart failure patients was significantly associated with spironolactone use (odds ratio (OR) (95% confidence interval (CI)) = 13.59 (11.63-15.88) in all and 11.05 (8.67-14.08) in those with information on New York Heart Association (NYHA) stage of disease). In the NYHA subpopulation, higher risk estimates were observed in short-term as compared with long-term users (OR (95%CI) = 13.00 (9.82-17.21) and 9.12 (6.78-12.26), respectively). Moreover, the association was stronger in older (≥70 years of age) as compared with younger patients (life practice than observed in clinical trials. Careful potassium level monitoring in concomitant users of spironolactone and ACE/ARB is necessary. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats

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    Lin CM

    2015-08-01

    Full Text Available Chien-Min Lin,1,* Jo-Ting Tsai,2,* Chen Kuei Chang,1 Juei-Tang Cheng,3 Jia-Wei Lin11Department of Neurosurgery, 2Department of Radiation Oncology, Shuang Ho Hospital-Taipei Medical University, 3Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan City, Taiwan*These authors contributed equally to this workBackground: Decrease of peroxisome proliferator-activated receptors-δ (PPARδ expression has been observed after spinal cord injury (SCI. Increase of PPARδ may improve the damage in SCI. Telmisartan, the antihypertensive agent, has been mentioned to increase the expression of PPARδ. Thus, we are going to screen the effectiveness of telmisartan in SCI for the development of it in clinical application.Methods: In the present study, we used compressive SCI in rats. Telmisartan was then used to evaluate the influence in rats after SCI. Change in PPARδ expression was identified by Western blots. Also, behavioral tests were performed to check the recovery of damage.Results: Recovery of damage from SCI was observed in telmisartan-treated rats. Additionally, this action of telmisartan was inhibited by GSK0660 at the dose sufficient to block PPARδ. However, metformin at the dose enough to activate adenosine monophosphate-activated protein kinase failed to produce similar action as telmisartan. Thus, mediation of adenosine monophosphate-activated protein kinase in this action of telmisartan can be rule out. Moreover, telmisartan reversed the expressions of PPARδ in rats with SCI.Conclusion: The obtained data suggest that telmisartan can improve the damage of SCI in rats through an increase in PPARδ expression. Thus, telmisartan is useful to be developed as an agent in the therapy of SCI.Keywords: PPARδ, AMPK, spinal cord injury, angiotensin receptor blocker, metformin

  14. Patterns of use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers among patients with acute myocardial infarction in China from 2001 to 2011: China PEACE-Retrospective AMI Study.

    Science.gov (United States)

    Liu, Jiamin; Masoudi, Frederick A; Spertus, John A; Wang, Qing; Murugiah, Karthik; Spatz, Erica S; Li, Jing; Li, Xi; Ross, Joseph S; Krumholz, Harlan M; Jiang, Lixin

    2015-02-23

    Chinese and U.S. guidelines recommend angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) for all patients with acute myocardial infarction (AMI) in the absence of contraindications as either a Class I or Class IIa recommendation. Little is known about the use and trends of ACEI/ARB therapy in China over the past decade. Using nationally representative data from the China Patient-centered Evaluative Assessment of Cardiac Events Retrospective Study of Acute Myocardial Infarction (China PEACE-Retrospective AMI Study), we assessed use of ACEI/ARB therapy in 2001, 2006, and 2011, overall and across geographic regions and strata of estimated mortality risk, and predictors of ACEI/ARB therapy, among patients with Class I indication by Chinese guidelines. The weighted rate of ACEI/ARB therapy increased from 62.0% in 2001 to 71.4% in 2006, decreasing to 67.6% in 2011. Use was low across all 5 geographic regions. By strata of estimated mortality risk, in 2001, rates of therapy increased with increasing risk; however, by 2011, this reversed and those at higher risk were less likely to be treated (70.7% in lowest-risk quintile vs. 63.5% in the highest-risk quintile; P<0.001). One third of Chinese AMI patients with Class I indications do not receive ACEI/ARB therapy during hospitalization, with little improvement in rates over time. Patients at higher mortality risk in 2011 were less likely to be treated, highlighting important opportunities to optimize the use of this cost-effective therapy. ClinicalTrials.gov. Unique identifier: NCT01624883. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  15. A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial: study protocol for a randomized double-blind controlled trial

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    Figueiredo Neto José A

    2011-02-01

    Full Text Available Abstract Background Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. Methods/design This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. Discussion The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials

  16. Dialysis-associated hypertension treated with Telmisartan--DiaTel: a pilot, placebo-controlled, cross-over, randomized trial.

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    Matthias Huber

    Full Text Available Treatment of hypertension in hemodialysis (HD patients is characterised by lack of evidence for both the blood pressure (BP target goal and the recommended drug class to use. Telmisartan, an Angiotensin receptor blocker (ARB that is metabolised in the liver and not excreted via HD extracorporeal circuit might be particularly suitable for HD patients. We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top of standard antihypertensive treatment excluding other Renin-Angiotensin-System (RAS blockers. In 29 patients after randomization we analysed BP after a treatment period of 8 weeks, while 13 started with telmisartan and 16 with placebo; after 8 weeks 11 continued with telmisartan and 12 with placebo after cross-over, respectively. Patients exhibited a significant reduction of systolic pre-HD BP from 141.9±21.8 before to 131.3±17.3 mmHg after the first treatment period with telmisartan or placebo. However, no average significant influence of telmisartan was observed compared to placebo. The latter may be due to a large inter-individual variability of BP responses reaching from a 40 mmHg decrease under placebo to 40 mmHg increase under telmisartan. Antihypertensive co-medication was changed for clinical reasons in 7 out of 21 patients with no significant difference between telmisartan and placebo groups. Our starting hypothesis, that telmisartan on top of standard therapy lowers systolic office BP in HD patients could not be confirmed. In conclusion, this small trial indicates that testing antihypertensive drug efficacy in HD patients is challenging due to complicated standardization of concomitant medication and other confounding factors, e.g. volume status, salt load and neurohormonal activation, that influence BP control in HD patients.Clinicaltrialsregister.eu 2005-005021-60.

  17. A PROSPECTIVE STUDY OF EFFECT OF TELMISARTAN (ANGIOTENSIN II RECEPTOR BLOCKER ON METABOLIC PARAMETERS IN HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME

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    Somesekhar

    2016-04-01

    Full Text Available BACKGROUND The metabolic syndrome is currently a major worldwide epidemic. It strongly associates with obesity, insulin resistance, type 2 diabetes, and cardiovascular diseases, which are major pathologies contributing to mortality and morbidity worldwide. The effect of PPAR-y on metabolic syndrome is significant it is critical regulator of adipogenesis the gain in PPAR-y is resulted in obesity but loss of PPAR–y by mutation is associated with loss of weight and insulin resistance. Telmisartan is an orally active, long-acting, non-peptide angiotensin type 1 (ATI receptor blocker. In addition to this, it has been identified as partial agonist/selective modulator of the nuclear hormone receptor PPAR-y. MATERIAL AND METHOD This is a prospective, randomised and open labelled 16 weeks study conducted in the Dept. of General Medicine, Konaseema Institute of Medical Science, Amalapuram. Present study is designed to study the effect of telmisartan on various metabolic parameters in hypertensive patients who fulfilled the criteria of metabolic syndrome. RESULT There was statistically significant change in all parameters most important was lipid profile; LDL concentration was decreased from 139.2 mg/dL to 120.2 mg/dL. Baseline triglyceride concentration was 161.0 mg/dL which was changed 152.8 mg/dL Total cholesterol was decreased from 203.2 to 193.8 mg/dL. CONCLUSION In our study, we have also found that use of telmisartan is associated with decrease in lipid concentration in addition to its effect on blood pressure regulation. But a long term study with high dose required of this drug is required because safety profile of this drug is better than thiazolidinedione. Financial part of this study is our limitation.

  18. Angiotensin receptor blockers are associated with lower mortality than ACE inhibitors in predialytic stage 5 chronic kidney disease: A nationwide study of therapy with renin-angiotensin system blockade.

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    Chih-Ching Lin

    Full Text Available Dual renin angiotensin system (RAS blockade using angiotensin-receptor blockers (ARBs in combination with angiotensin converting enzyme inhibitors (ACEIs is reported to improve proteinuria in both diabetic and non-diabetic patients. However, its renoprotective effect and safety remain uncertain in patients with advanced chronic kidney disease (CKD. From January 1, 2000 through June 30, 2009, we enrolled 14,117 pre-dialytic stage 5 CKD patients with serum creatinine >6mg/dL and hematocrit <28% under the treatment with erythropoiesis stimulating agents and RAS blockade. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs against the commencement of long-term dialysis and all-cause mortality for ACEI/ARB users. Over a median follow-up of 7 months, 9,867 patients (69.9% required long-term dialysis and 2,805 (19.9% died before progression to end-stage renal disease requiring dialysis. In comparison with the ARB-only users, dual blockade with ACEIs and ARBs was associated with a significantly higher risk of (1 death in all CKD patients (HR = 1.49, [95%CI, 1.30-1.71]; P = 0.02 and in diabetic subgroup (HR = 1.58, [95%CI, 1.34-1.86]; P = 0.02; (2 composite endpoint of long-term dialysis or death in diabetic subgroup (HR = 1.10, [95%CI, 1.01-1.20]; P = 0.04; (3 hyperkalemia-associated hospitalization in non-diabetic subgroup (HR, 2.74, [95%CI, 1.05-7.15]; P = 0.04. However, ACEIs users were associated with higher mortality than ARBs users in all CKD patients (HR = 1.17, [95%CI, 1.07-1.27]; P = 0.03 and in diabetic subgroup (HR = 1.32, [95%CI, 1.18-1.48]; P = 0.03. Monotherapy of RAS blockade, especially ARB, is more effective and safer than dual RAS blockade in pre-dialytic stage 5 CKD patients.

  19. Distinct properties of telmisartan on agonistic activities for peroxisome proliferator-activated receptor γ among clinically used angiotensin II receptor blockers: drug-target interaction analyses.

    Science.gov (United States)

    Kakuta, Hirotoshi; Kurosaki, Eiji; Niimi, Tatsuya; Gato, Katsuhiko; Kawasaki, Yuko; Suwa, Akira; Honbou, Kazuya; Yamaguchi, Tomohiko; Okumura, Hiroyuki; Sanagi, Masanao; Tomura, Yuichi; Orita, Masaya; Yonemoto, Takako; Masuzaki, Hiroaki

    2014-04-01

    A proportion of angiotensin II type 1 receptor blockers (ARBs) improves glucose dyshomeostasis and insulin resistance in a clinical setting. Of these ARBs, telmisartan has the unique property of being a partial agonist for peroxisome proliferator-activated receptor γ (PPARγ). However, the detailed mechanism of how telmisartan acts on PPARγ and exerts its insulin-sensitizing effect is poorly understood. In this context, we investigated the agonistic activity of a variety of clinically available ARBs on PPARγ using isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) system. Based on physicochemical data, we then reevaluated the metabolically beneficial effects of telmisartan in cultured murine adipocytes. ITC and SPR assays demonstrated that telmisartan exhibited the highest affinity of the ARBs tested. Distribution coefficient and parallel artificial membrane permeability assays were used to assess lipophilicity and cell permeability, for which telmisartan exhibited the highest levels of both. We next examined the effect of each ARB on insulin-mediated glucose metabolism in 3T3-L1 preadipocytes. To investigate the impact on adipogenesis, 3T3-L1 preadipocytes were differentiated with each ARB in addition to standard inducers of differentiation for adipogenesis. Telmisartan dose-dependently facilitated adipogenesis and markedly augmented the mRNA expression of adipocyte fatty acid-binding protein (aP2), accompanied by an increase in the uptake of 2-deoxyglucose and protein expression of glucose transporter 4 (GLUT4). In contrast, other ARBs showed only marginal effects in these experiments. In accordance with its highest affinity of binding for PPARγ as well as the highest cell permeability, telmisartan superbly activates PPARγ among the ARBs tested, thereby providing a fresh avenue for treating hypertensive patients with metabolic derangement.

  20. Urine Eicosanoids in the Metabolic Abnormalities, Telmisartan, and HIV Infection (MATH Trial.

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    Catherine N Le

    Full Text Available Arachidonic acid metabolites (eicosanoids reflect oxidative stress and vascular health and have been associated with anthropometric measures and sex differences in cross-sectional analyses of HIV-infected (HIV+ persons. Telmisartan is an angiotensin receptor blocker and PPAR-γ agonist with potential anti-inflammatory and metabolic benefits. We assessed telmisartan's effects on urine eicosanoids among HIV+ adults with central adiposity on suppressive antiretroviral therapy enrolled in a prospective clinical trial.Thirty-five HIV+ adults (15 women; 20 men completed 24 weeks of open-label oral telmisartan 40mg daily. Lumbar computed tomography quantified visceral (VAT and subcutaneous (SAT abdominal adipose tissue. Urine F2-isoprostane (F2-IsoP, prostaglandin E2 (PGE-M, prostacyclin (PGI-M, and thromboxane B2 (TxB-M were quantified at baseline and 24 weeks using gas/liquid chromatography-mass spectroscopy. Mann-Whitney-U tests compared sub-group differences; Spearman's rho assessed correlations between clinical factors and eicosanoid levels.Median PGE-M increased on telmisartan (p5% VAT (+3.7 ng/mg cr, p5% SAT (+1.7 ng/mg cr, p = 0.04. Median baseline F2-IsoP and TxB-M were slightly higher in women (both between-group p = 0.08 and did not change on telmisartan.Urine PGE-M increased with 24 weeks of telmisartan in virally suppressed, HIV+ adults with central adiposity. Associations with favorable fat redistribution suggest increased PGE-M may reflect a beneficial response.

  1. Effects of withdrawing vs continuing renin-angiotensin blockers on incidence of acute kidney injury in patients with renal insufficiency undergoing cardiac catheterization: Results from the Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker and Contrast Induced Nephropathy in Patients Receiving Cardiac Catheterization (CAPTAIN) trial.

    Science.gov (United States)

    Bainey, Kevin R; Rahim, Sherali; Etherington, Krystal; Rokoss, Michael L; Natarajan, Madhu K; Velianou, James L; Brons, Sonya; Mehta, Shamir R

    2015-07-01

    It is unclear if holding angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) prior to coronary angiography reduces contrast-induced acute kidney injury (AKI). We undertook a randomized trial to investigate the effect of holding ACEI/ARB therapy prior to coronary angiography on the incidence of AKI. We randomly assigned 208 patients with moderate renal insufficiency (creatinine ≥ 1.7mg/dL within 3 months and/or documented creatinine ≥ 1.5mg/dL within 1 week before cardiac catheterization) to hold ACEI/ARB ≥24 hours preprocedure or continue ACEI/ARB. The primary outcome was the incidence of AKI defined as an absolute rise in serum creatinine of ≥0.5mg/dL from baseline and/or a relative rise in serum creatinine of ≥25% compared with baseline measured at 48 to 96 hours postcardiac catheterization. All patients were taking an ACEI (72.1%) or ARB (27.9%) prior to randomization. At 48 to 96 hours, the primary outcome occurred in 18.4% of patients who continued ACEI/ARB compared with 10.9% of the patients who held ACEI/ARB (hazard ratio 0.59, 95% CI 0.30-1.19, P = .16). In a prespecified secondary outcome, there was a lower rise in mean serum creatinine after the procedure in patients who held ACEI/ARB (0.3 ± 0.5 vs 0.1 ± 0.3mg/dL, P = .03). The clinical composite of death, myocardial infarction, ischemic stroke, congestive heart failure, rehospitalization for cardiovascular cause, or need for dialysis preprocedure occurred in 3.9% who continued ACEI/ARB compared with 0% who held the ACEI/ARB (hazard ratio 0.11, 95% CI 0.01-2.96, P = .06). In this pilot study of patients with moderate renal insufficiency undergoing cardiac catheterization, with-holding ACEI/ARB resulted in a non-significant reduction in contrast-induced AKI and a significant reduction in post-procedural rise of creatinine. This low cost intervention could be considered when referring a patient for cardiac catheterization. Copyright © 2015 Elsevier Inc. All

  2. Comparative study of high dose mono-therapy of amlodipine or telmisartan, and their low dose combination in mild to moderate hypertension.

    Science.gov (United States)

    Goyal, Jaswant; Khan, Zafer Yab; Upadhyaya, Prerna; Goyal, Barkha; Jain, Shipra

    2014-06-01

    Hypertension is one of the major public health challenges worldwide. Angiotensin receptor blockers (ARBs) and Calcium channel blockers (CCBs) are among the first line antihypertensive drugs. However, optimal treatment strategies in mild to moderate hypertensives who failed to achieve blood pressure (BP) control with low-dose mono-therapy are not well established. This study was done to compare efficacy and safety of high dose mono-therapy of Amlodipine, Telmisartan and their low dose combination in mild to moderate hypertensives who failed to achieve BP control with low dose mono-therapy of either drug. A total of 96 patients, fulfilling inclusion and exclusion criteria were enrolled in the study after obtaining informed consent. Patients were randomized into three treatment groups i.e. Telmisartan 80 mg, Amlodipine 10 mg and low dose combination of Telmisartan 40 mg +Amlodipine 5 mg once daily for two months. The systolic BP, Diastolic BP, and ADRs were recorded at 0, 2, 4, 8 weeks. In the present study, significant reduction of mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP) was seen in all the three treatment groups. Low dose combination of Amlodipine 5 mg and Telmisartan 40 mg showed statistically significant reduction in SBP as compared to Telmisartan 80 mg mono-therapy and in DBP as compared to Amlodipine 10 mg mono-therapy. Maximum adverse drug reactions (ADRs) were reported in Amlodipine mono-therapy group, like ankle oedema, constipation, headache and fatigue. In term of BP control, low-dose combination therapy appears a better therapeutic approach than high-dose mono-therapy.

  3. Correction: Kikuchi, K., et al., Potential of the Angiotensin Receptor Blockers (ARBs Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke. Int. J. Mol. Sci. 2013, 14, 18899–18924.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Kikuchi

    2014-03-01

    Full Text Available The original version of the paper [1] reports that “This ACTIVE I study was supported by Pfizer” (Page 18905. However, the sponsors of the ACTIVE I study were actually Bristol-Myers Squibb and Sanofi-Aventis rather than Pfizer.

  4. Angiotensin Receptors, Autoimmunity, and Preeclampsia1

    OpenAIRE

    Xia, Yang; Zhou, Cissy Chenyi; Ramin, Susan M.; Kellems, Rodney E.

    2007-01-01

    Preeclampsia is a pregnancy-induced hypertensive disorder that causes substantial maternal and fetal morbidity and mortality. Despite being a leading cause of maternal death and a major contributor to maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia are poorly understood. Recent studies indicate that women with preeclampsia have autoantibodies that activate the angiotensin receptor, AT1, and that autoantibody-mediated receptor activation contri...

  5. Prospects for angiotensin receptor blockers in diabetic retinopathy

    DEFF Research Database (Denmark)

    Sjølie, Anne Katrin

    2007-01-01

    Retinopathy is the most common microvascular complication of diabetes mellitus, and is an important cause of blindness worldwide. Clinical trials have demonstrated that tight metabolic control inhibits the progression of retinopathy. Good blood pressure control has been shown to be protective...... in type 2 diabetes, and it may also reduce proliferative retinopathy in type 1 diabetes. However, such control is often difficult to achieve in clinical practice, and may be associated with problems such as hypoglycaemia. New therapies are therefore needed to reduce the risk of retinopathy....... There is growing evidence that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of diabetic retinopathy, and this has led to interest in RAS inhibitors as agents to prevent retinopathy. Several trials have suggested that ACE inhibitor therapy can inhibit progression of retinopathy...

  6. Trends in prescribing and persistence with antihypertensive therapy: results of the study PAPEETE (Population-based Analysis of Persistence and Economics of treatment with telmisartan study

    Directory of Open Access Journals (Sweden)

    Francesco Vittorio Costa

    2009-12-01

    Full Text Available This paper summarizes the results of the PAPEETE study (Population-based Analysis of PErsistence with treatment and Economics of TElmisartan that assessed trends in prescriptions, determinants and timing of treatment discontinuation and/or changes in antihypertensive drug therapy in a cohort of hypertensive patients living in Pavia. In the study were included all new users 18 years old or over receiving a first prescription for diuretics, beta-blockers, calcium channel-blockers, ACE inhibitors (ACEi or angiotensin receptor blockers (ARBs between 1 January 2003 and 31 December 2006. The follow-up period for each patient was 12 months starting from enrolment date. Based in the presence of continuous therapy, patients were defined as persistent and non-persistent users. A total of 61,493 patients was included in the study of whom 11.2% were persistent. Persistence with the treatment seems to be associated with patient-related factors and with the class of anti-hypertensive drug initially prescribed with the lowest persistence to antihypertensive treatment with diuretics (3.0% and the highest with ARBs (18.8%.

  7. TELMISARTAN IN THE TREATMENT OF ARTERIAL HYPERTENSION. CASE STUDY

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2015-12-01

    Full Text Available Data on angiotensin II receptor blockers, one of the main drug classes used in cardiology , are presented. The advantages of this drugs class are highlighted with the focus on telmisartan. Additionally clinical example of successful telmisartan application in patients with hypertension, high risk of cardiovascular complications, and obesity is presented.

  8. TELMISARTAN IN THE TREATMENT OF ARTERIAL HYPERTENSION. CASE STUDY

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2012-01-01

    Full Text Available Data on angiotensin II receptor blockers, one of the main drug classes used in cardiology , are presented. The advantages of this drugs class are highlighted with the focus on telmisartan. Additionally clinical example of successful telmisartan application in patients with hypertension, high risk of cardiovascular complications, and obesity is presented.

  9. Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration.

    NARCIS (Netherlands)

    Pitcher, A.; Emberson, J.; Lacro, R.V.; Sleeper, L.A.; Stylianou, M.; Mahony, L.; Pearson, G.D.; Groenink, M.; Mulder, B.J.; Zwinderman, A.H.; Backer, J. De; Paepe, A.M. De; Arbustini, E.; Erdem, G.; Jin, X.Y.; Flather, M.D.; Mullen, M.J.; Child, A.H.; Forteza, A.; Evangelista, A.; Chiu, H.H.; Wu, M.H.; Sandor, G.; Bhatt, A.B.; Creager, M.A.; Devereux, R.B.; Loeys, B.L.; Forfar, J.C.; Neubauer, S.; Watkins, H.; Boileau, C.; Jondeau, G.; Dietz, H.C.; Baigent, C.

    2015-01-01

    RATIONALE: A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a

  10. Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial: rationale, methods and design of a multicentre, randomised- and placebo-controlled clinical trial (NCT00120003)

    DEFF Research Database (Denmark)

    Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun Margrethe

    2010-01-01

    Elevated blood pressure following acute stroke is common, and yet early antihypertensive treatment is controversial. ACCESS suggested a beneficial effect of the angiotensin receptor blocker candesartan in the acute phase of stroke, but these findings need to be confirmed in new, large trials. AIMS......, Sweden, Denmark, Belgium, Germany, Poland, Lithuania, Estonia and Finland. STUDY OUTCOMES: There are two co-primary effect variables: • Functional status at 6-months, measured by the modified Rankin Scale, and • vascular death, myocardial infarction or stroke during the first 6-months. Secondary outcome...

  11. Effect of telmisartan on functional outcome, recurrence, and blood pressure in patients with acute mild ischemic stroke: a PRoFESS subgroup analysis

    DEFF Research Database (Denmark)

    Bath, Philip M W; Martin, Reneé H; Palesch, Yuko

    2009-01-01

    prevention trial assessed BP-lowering and antiplatelet strategies in 20 332 patients; 1360 were enrolled within 72 hours of ischemic stroke, with telmisartan (angiotensin receptor antagonist, 80 mg/d, n=647) vs placebo (n=713). For this nonprespecified subgroup analysis, the primary outcome was functional......, 1.40; 95% CI, 0.68-2.89; P=0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mm Hg, difference 6 to 7 mm Hg and 2 to 4 mm Hg; P...

  12. Telmisartan attenuates chronic ciclosporin A nephrotoxicity in a pig model

    DEFF Research Database (Denmark)

    Cibulskyte, Donata; pedersen, michael; Hørlyck, Arne

    2007-01-01

    of angiotensin II (Ang II) receptor blocker telmisartan on chronic CsA nephrotoxicity in pigs. METHODS: Fourteen Göttingen minipigs aged 12-14 months were included: pigs received either CsA 10 mg/kg/day (n = 7) or CsA 10 mg/kg/day + telmisartan 40 mg/day (n = 7) orally for 12 months. At week 0, 12, 31, 38, 47...... (RBF). Kidney tissue biopsies were used for conventional histological examination. RESULTS: Plasma Ang II levels were significantly higher during telmisartan treatment. Interstitial fibrosis and glomerulosclerosis occurred in both groups, but were attenuated in the telmisartan-treated pigs (P = 0.......064). A significant increase in renal volume was seen in both groups, but tended to be lower in the CsA + telmisartan pigs at 54 weeks (P = 0.097). Telmisartan did not reduce MAP, RBF or rGFR. CONCLUSIONS: Long-term CsA treatment causes histopathological changes in the porcine kidney similar to those observed...

  13. Angiotensin receptor agonistic autoantibodies and hypertension: preeclampsia and beyond.

    Science.gov (United States)

    Xia, Yang; Kellems, Rodney E

    2013-06-21

    Hypertensive disorders are life-threatening diseases with high morbidity and mortality, affecting billions of individuals worldwide. A multitude of underlying conditions may contribute to hypertension, thus the need for a plethora of treatment options to identify the approach that best meets the needs of individual patients. A growing body of evidence indicates that (1) autoantibodies that bind to and activate the major angiotensin II type I (AT₁) receptor exist in the circulation of patients with hypertensive disorders, (2) these autoantibodies contribute to disease pathophysiology, (3) antibody titers correlate to the severity of the disease, and (4) efforts to block or remove these pathogenic autoantibodies have therapeutic potential. These autoantibodies, termed AT₁ agonistic autoantibodies have been extensively characterized in preeclampsia, a life-threatening hypertensive condition of pregnancy. As reviewed here, these autoantibodies cause symptoms of preeclampsia when injected into pregnant mice. Somewhat surprisingly, these auto antibodies also appear in 3 animal models of preeclampsia. However, the occurrence of AT₁ agonistic autoantibodies is not restricted to pregnancy. These autoantibodies are prevalent among kidney transplant recipients who develop severe transplant rejection and malignant hypertension during the first week after transplantation. AT₁ agonistic autoantibodies are also highly abundant among a group of patients with essential hypertension that are refractory to standard therapy. More recently these autoantibodies have been seen in patients with the autoimmune disease, systemic sclerosis. These 3 examples extend the clinical impact of AT₁ agonistic autoantibodies beyond pregnancy. Research reviewed here raises the intriguing possibility that preeclampsia and other hypertensive conditions are autoimmune diseases characterized by the presence of pathogenic autoantibodies that activate the major angiotensin receptor, AT₁. These

  14. The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST)

    DEFF Research Database (Denmark)

    Sandset, Else Charlotte; Bath, Philip M W; Boysen, Gudrun

    2011-01-01

    within 30 h of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3 to 7. Randomisation was stratified by centre, with blocks of six packs of candesartan or placebo. Patients and investigators were masked...... to treatment allocation. There were two co-primary effect variables: the composite endpoint of vascular death, myocardial infarction, or stroke during the first 6 months; and functional outcome at 6 months, as measured by the modified Rankin Scale. Analyses were by intention to treat. The study is registered...... significant at p≤0·025 level]). The observed effects were similar for all prespecified secondary endpoints (including death from any cause, vascular death, ischaemic stroke, haemorrhagic stroke, myocardial infarction, stroke progression, symptomatic hypotension, and renal failure) and outcomes (Scandinavian...

  15. Renoprotective effect of calcium channel blockers

    Directory of Open Access Journals (Sweden)

    Dimković Nada

    2009-01-01

    Full Text Available The advancing chronic renal failure is at most the consequence of secondary haemodynamic and metabolic factors as intraglomerular hypertension and glomerular hypertrophy. Although tight blood pressure control is the major preventive mechanism for progressive renal failure, ACE inhibitors and angiotensin receptor blockers have some other renoprotective mechanisms beyond the blood pressure control. That is why these two groups of antihypertensive drugs traditionally have advantages in treating renal patients especially those with proteinuria over 400-1000 mg/day. Even if earlier experimental studies have shown renoprotective effect of calcium channel blockers, later clinical studies did not prove that calcium channel blockers have any advantages in renal protection over ACE inhibitors given as monotherapy or in combination with ACE inhibitors. It was explained by action of calcium channel blockers on afferent but not on efferent glomerular arterioles; a well known mechanism that leads to intraglomerular hypertension. New generations of dihydropiridine calcium channel blockers can dilate even efferent arterioles not causing unfavorable haemodynamic disturbances. This finding was confirmed in clinical studies which showed that renoprotection established by calcium channel blockers was not inferior to that of ACE inhibitors and that calcium channel blockers and ACE inhibitors have additive effect on renoprotection. Newer generation of dihydropiridine calcium channel blockers seem to offer more therapeutic possibilities in renoprotection by their dual action on afferent and efferent glomerular arterioles and, possibly by other effects beyond the blood pressure control.

  16. Angiotensin receptor-neprilysin inhibitors: clinical potential in heart failure and beyond

    Directory of Open Access Journals (Sweden)

    Singh JSS

    2015-06-01

    Full Text Available Jagdeep SS Singh, Chim C Lang Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK Abstract: Heart failure remains a major concern across the globe as life expectancies and delivery of health care continue to improve. There has been a dearth of new developments in heart failure therapies in the last decade until last year, with the release of the results from the PARADIGM-HF Trial heralding the arrival of a promising new class of drug, ie, the angiotensin receptor-neprilysin inhibitor. In this review, we discuss the evolution of our incremental understanding of the neurohormonal mechanisms involved in the pathophysiology of heart failure, which has led to our success in modulating its various pathways. We start by examining the renin-angiotensin-aldosterone system, followed by the challenges of modulating the natriuretic peptide system. We then delve deeper into the pharmacology and mechanisms by which angiotensin receptor-neprilysin inhibitors achieve their significant cardiovascular benefits. Finally, we also consider the potential application of this new class of drug in other areas, such as heart failure with preserved ejection fraction, hypertension, patients with renal impairment, and following myocardial infarction. Keywords: heart failure, angiotensin receptor-neprilysin inhibitor, heart failure with preserved ejection fraction, nesiritide, candoxatril, omapatrilat, hypertension, renal impairment, myocardial infarction

  17. Angiotensin receptor blockade improves cardiac mitochondrial activity in response to an acute glucose load in obese insulin resistant rats

    Directory of Open Access Journals (Sweden)

    Max Thorwald

    2018-04-01

    Full Text Available Hyperglycemia increases the risk of oxidant overproduction in the heart through activation of a multitude of pathways. Oxidation of mitochondrial enzymes may impair their function resulting in accumulation of intermediates and reverse electron transfer, contributing to mitochondrial dysfunction. Furthermore, the renin-angiotensin system (RAS becomes inappropriately activated during metabolic syndrome, increasing oxidant production. To combat excess oxidant production, the transcription factor, nuclear factor erythriod-2- related factor 2 (Nrf2, induces expression of many antioxidant genes. We hypothesized that angiotensin II receptor type 1 (AT1 blockade improves mitochondrial function in response to an acute glucose load via upregulation of Nrf2. To address this hypothesis, an oral glucose challenge was performed in three groups prior to dissection (n = 5–8 animals/group/time point of adult male rats: 1 Long Evans Tokushima Otsuka (LETO; lean strain-control, 2 insulin resistant, obese Otsuka Long Evans Tokushima Fatty (OLETF, and 3 OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d × 6 weeks. Hearts were collected at T0, T60, and T120 minutes post-glucose infusion. ARB increased Nrf2 binding 32% compared to OLETF at T60. Total superoxide dismutase (SOD and catalase (CAT activities were increased 45% and 66% respectively in ARB treated animals compared to OLETF. Mitochondrial enzyme activities of aconitase, complex I, and complex II increased by 135%, 33% and 66%, respectively in ARB compared to OLETF. These data demonstrate the protective effects of AT1 blockade on mitochondrial function during the manifestation of insulin resistance suggesting that the inappropriate activation of AT1 during insulin resistance may impair Nrf2 translocation and subsequent antioxidant activities and mitochondrial function. Keywords: Angiotensin II, Mitochondria, Cardiac, Antioxidant enzymes, TCA cycle

  18. Individualized prediction of the effect of angiotensin receptor blockade on renal and cardiovascular outcomes in patients with diabetic nephropathy.

    Science.gov (United States)

    van der Sande, N G C; Dorresteijn, J A N; Visseren, F L J; Dwyer, J P; Blankestijn, P J; van der Graaf, Y; Heerspink, H L J

    2016-11-01

    To predict individualized treatment effects of angiotensin receptor blockers (ARBs) on cardiovascular and renal complications in order to help clinicians and patients assess the benefit of treatment (or adherence) and estimate remaining disease risk. In patients with diabetic nephropathy, the 3-year treatment effect of ARBs was predicted in terms of absolute risk reduction (ARR) for end-stage renal disease (ESRD) and cardiovascular disease (CVD; i.e. myocardial infarction, stroke, hospitalization for heart failure) and all-cause mortality. Competing-risk-adjusted proportional hazard models were developed based on the Irbesartan Diabetic Nephropathy Trial (IDNT) and externally validated in the Reduction of Endpoints NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. Predictors included in the model were age, sex, smoking sex, systolic blood pressure, urinary albumin/creatinine ratio, estimated glomerular filtration rate, albumin and phosphorus. The median predicted 3-year risk without treatment was 6.0% for ESRD and 28.0% for CVD and mortality. The median [interquartile range (IQR)] predicted 3-year ARR was 1.2 (0.4-3.1)% for ESRD and 2.2 (1.8-2.6)% for CVD and mortality, resulting in a combined ARR of 3.4 (2.4-5.5)%. The remaining disease risk was 4.7 (IQR 1.7-12.8)% for ESRD and 25.8% (IQR 20.3-31.9)% for CVD and mortality. The combined effects of ARBs on ESRD and CVD and mortality in patients with diabetic nephropathy vary considerably between patients. A substantial proportion of patients remain at high risk for both outcomes despite ARB treatment. © 2016 John Wiley & Sons Ltd.

  19. New standards in hypertension and cardiovascular risk management: focus on telmisartan

    Directory of Open Access Journals (Sweden)

    Domenico Galzerano

    2010-03-01

    Full Text Available Domenico Galzerano1, Cristina Capogrosso4, Sara Di Michele2, Antonio Galzerano1, Paola Paparello1, Diana Lama3, Carlo Gaudio21Department of Cardiology, San Gennaro Hospital, Naples, Italy; 2Department of Heart and Great Vessels, A. Reale, La Sapienza University, Rome, Italy; 3V Division of Internal Medicine, II University, Naples, Italy; 4Cardiology Division, San Giovanni Bosco Hospital, Naples, ItalyAbstract: Blockade of the renin–angiotensin system is an important approach in managing high blood pressure, and has increasingly been shown to affect cardiovascular disease processes mediated by angiotensin II throughout the cardiovascular and renal continua. Telmisartan is an angiotensin II receptor blocker (ARB displaying unique pharmacologic properties, including a longer half life than any other ARB, that result in large and sustained reductions of blood pressure. In patients with mild-to-moderate hypertension, telmisartan has proved superior to other antihypertensive agents (valsartan, losartan, ramipril, perindopril, and atenolol in controlling blood pressure particularly towards the end of the dosing interval. There is also clinical evidence that telmisartan reduces left ventricular hypertrophy, reduces arterial stiffness and the recurrence of atrial fibrillation, and confers renoprotection. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET® study has demonstrated that telmisartan has similar cardiovascular protective effects to ramipril in a large, high-risk patient population but was better tolerated. The powerful and sustained blood pressure control apparent in clinical trials, together with cardiovascular protection and tolerability demonstrated in ONTARGET® means that telmisartan may be a preferred option for patients with hypertension.Keywords: angiotensin II receptor blocker, cardiovascular disease, hypertension, renin–angiotensin system, telmisartan

  20. Glucocorticoid-Induced Fetal Programming Alters the Functional Complement of Angiotensin Receptors Subtypes within the Kidney

    OpenAIRE

    Gwathmey, TanYa M.; Shaltout, Hossam A.; Rose, James C.; Diz, Debra I.; Chappell, Mark C.

    2011-01-01

    We examined the impact of fetal programming on the functional responses of renal angiotensin receptors. Fetal sheep were exposed in utero to betamethasone (BMX; 0.17 mg/kg) or control (CON) at 80–81 days gestation with full term delivery. Renal nuclear and plasma membrane fractions were isolated from 1.0–1.5 year old sheep for receptor binding and fluorescence detection of reactive oxygen species (ROS) or nitric oxide (NO). Mean arterial blood pressure and blood pressure variability were sign...

  1. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies.

    Directory of Open Access Journals (Sweden)

    Nofar Torika

    Full Text Available The circulating renin-angiotensin system (RAS, including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker on tumor necrosis factor-α (TNF-α, interleukin 1-β (IL1-β and nitric oxide (NO release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor. Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the

  2. Clinical effectiveness of telmisartan alone or in combination therapy for controlling blood pressure and vascular risk in the elderly

    Directory of Open Access Journals (Sweden)

    Bodh I Jugdutt

    2010-12-01

    Full Text Available Bodh I JugduttDivision of Cardiology, Department of Medicine, University of Alberta and Hospital, Edmonton, CanadaAbstract: Elderly patients (age≥65 years with hypertension are at high risk for vascular complications, especially when diabetes is present. Antihypertensive drugs that inhibit the renin-angiotensin system have been shown to be effective for controlling blood pressure in adult and elderly patients. Importantly, renin-angiotensin system inhibitors were shown to have benefits beyond their classic cardioprotective and vasculoprotective effects, including reducing the risk of new-onset diabetes and associated cardiovascular effects. The discovery that the renin-angiotensin system inhibitor and angiotensin II type 1 (AT1 receptor blocker (ARB, telmisartan, can selectively activate the peroxisome proliferator-activated receptor-γ (PPARγ, an established antidiabetic drug target provides the unique opportunity to prevent and treat cardiovascular complications in high-risk elderly patients with hypertension and new-onset diabetes. Two large clinical trials, ONTARGET (Ongoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial and TRANSCEND (Telmisartan Randomized AssessmeNt Study in ACE-I iNtolerant subjects with cardiovascular disease have assessed the cardioprotective and antidiabetic effects of telmisartan. The collective data suggest that telmisartan is a promising drug for controlling hypertension and reducing vascular risk in high-risk elderly patients with new-onset diabetes.Keywords: elderly, hypertension, telmisartan, angiotensin II type 1 receptor blocker, peroxisome proliferator-activated receptor-γ, diabetes, vascular risk

  3. Pharmacokinetics of a telmisartan, amlodipine and ...

    African Journals Online (AJOL)

    Conclusion: A formulated FDC tablet containing a telmisartan/amlodipine/HCTZ combination (80/10/25mg) was bioequivalent to a co-administrated commercially available telmisartan/amlodipine combination and HCTZ tablets at equivalent concentrations. Keywords: Fixed-dose combination, Hypertension, Telmisartan, ...

  4. Effects of telmisartan and olmesartan on insulin sensitivity and renal function in spontaneously hypertensive rats fed a high fat diet

    Directory of Open Access Journals (Sweden)

    Hayato Yanagihara

    2016-07-01

    Full Text Available Although telmisartan, an angiotensin II receptor blocker (ARB, has an agonistic action for proliferator-activated receptor (PPAR-γ in vitro, it remains to be determined whether telmisartan exerts such an action in vivo using a non-toxic dose (<5 mg/kg in rats. To address the issue, telmisartan (2 mg/kg and olmesartan (2 mg/kg, another ARB without PPAR-γ agonistic action, were given to spontaneously hypertensive rats (SHR fed a high fat diet (HFD. HFD decreased plasma adiponectin, and caused insulin resistance, hypertriglyceridemia and renal damage, which were improved by ARBs. Protective effects of telmisartan and olmesartan did not significantly differ. In addition, in vitro study showed that 1 μM of telmisartan did not elevate the mRNA expression of adipose protein 2, which is a PPAR-γ-stimulated adipogenic marker gene, in preadipocytes with 3% albumin. To obtain 1 μM of plasma concentration, oral dose of telmisartan was calculated to be 6 mg/kg, which indicates that PPAR-γ agonistic action is negligible with a non-toxic dose of telmisartan (<5 mg/kg in rats. This study showed that 2 mg/kg of telmisartan and olmesartan ameliorated insulin resistance, hypertriglyceridemia and renal damage in SHR fed a HFD. As beneficial effects of telmisartan and olmesartan did not significantly differ, these were mediated through the PPAR-γ-independent actions.

  5. Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction

    NARCIS (Netherlands)

    Voors, Adriaan A.; Gori, Mauro; Liu, Licette C. Y.; Claggett, Brian; Zile, Michael R.; Pieske, Burkert; McMurray, John J. V.; Packer, Milton; Shi, Victor; Lefkowitz, Martin P.; Solomon, Scott D.

    BackgroundIncreases in serum creatinine with renin-angiotensin-aldosterone system (RAAS) inhibitors can lead to unnecessary discontinuation of these agents. The dual-acting angiotensin receptor neprilysin inhibitor LCZ696 improves clinical outcome patients with heart failure with reduced ejection

  6. The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers

    DEFF Research Database (Denmark)

    Schievink, Bauke; de Zeeuw, Dick; Parving, Hans-Henrik

    2015-01-01

    , haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative...

  7. The Role of Apelin on the Alleviative Effect of Angiotensin Receptor Blocker in Unilateral Ureteral Obstruction-Induced Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Masashi Nishida

    2012-03-01

    Full Text Available Background: Apelin is a selective endogenous ligand of the APJ receptor, which genetically has closest identity to the angiotensin II type 1 receptor (AT-1. The effects of the apelin/APJ system on renal fibrosis still remain unclear. Methods: We examined the effects of the apelin/APJ system on renal fibrosis during AT-1 blockade in a mouse unilateral ureteral obstruction (UUO model. Results: We obtained the following results: (1 At UUO day 7, mRNA expressions of apelin/APJ and phosphorylations of Akt/endothelial nitric oxide synthase (eNOS in the UUO kidney were increased compared to those in the nonobstructed kidney. (2 AT-1 blockade by the treatment with losartan resulted in a further increase of apelin mRNA as well as phosphorylations of Akt/eNOS proteins, and this was accompanied by alleviated renal interstitial fibrosis, decreased myofibroblast accumulation, and a decreased number of interstitial macrophages. (3 Blockade of the APJ receptor by the treatment with F13A during losartan administration completely abrogated the effects of losartan in the activation of the Akt/eNOS pathway and the amelioration of renal fibrosis. (4 Inhibition of NOS by the treatment with L-NAME also resulted in a further increase in renal fibrosis compared to the control group. Conclusion: These results suggest that increased nitric oxide production through the apelin/APJ/Akt/eNOS pathway may, at least in part, contribute to the alleviative effect of losartan in UUO-induced renal fibrosis.

  8. Rational Design, Efficient Synthesis, Biological Evaluation of New Ν,Ν'-bis-substituted Butylimidazole Analogs as Potent Angiotensin Receptor Blockers

    Czech Academy of Sciences Publication Activity Database

    Agelis, G.; Resvani, A.; Koukoulitsa, C.; Afantitis, A.; Melagraki, G.; Siafaka, A.; Gkini, E.; Tůmová, Tereza; Spyridaki, K.; Kalavrizioti, D.; Androutsou, M-E.; Slaninová, Jiřina; Liapakis, G.; Vlahakos, D.; Mavromoustakos, T.; Matsoukas, J.

    2012-01-01

    Roč. 18, S1 (2012), S123-S123 ISSN 1075-2617. [European Peptide Symposium /32./. 02.09.2012-07.09.2012, Athens] Institutional research plan: CEZ:AV0Z40550506 Keywords : angiotensin II AT1 receptor * in vitro * antagonism * inhibitor * in vitro antagonism * synthesis Subject RIV: CE - Biochemistry

  9. Glucocorticoid-induced fetal programming alters the functional complement of angiotensin receptor subtypes within the kidney.

    Science.gov (United States)

    Gwathmey, TanYa M; Shaltout, Hossam A; Rose, James C; Diz, Debra I; Chappell, Mark C

    2011-03-01

    We examined the impact of fetal programming on the functional responses of renal angiotensin receptors. Fetal sheep were exposed in utero to betamethasone (BMX; 0.17 mg/kg) or control (CON) at 80 to 81 days gestation with full-term delivery. Renal nuclear and plasma membrane fractions were isolated from sheep age 1.0 to 1.5 years for receptor binding and fluorescence detection of reactive oxygen species (ROS) or nitric oxide (NO). Mean arterial blood pressure and blood pressure variability were significantly higher in the BMX-exposed adult offspring versus CON sheep. The proportion of nuclear AT(1) receptors sensitive to losartan was 2-fold higher (67 ± 6% vs 27 ± 9%; Psheep (16 ± 3% vs 6 ± 4%; Pfetal programming.

  10. Molecule-specific Effects of Angiotensin II–Receptor Blockers Independent of the Renin–Angiotensin System

    Czech Academy of Sciences Publication Activity Database

    Kurtz, T. W.; Pravenec, Michal

    2008-01-01

    Roč. 21, č. 8 (2008), s. 852-859 ISSN 0895-7061 R&D Projects: GA MŠk(CZ) 1M0520; GA MZd(CZ) NR8545 Grant - others:EURATOOLS(XE) LSHG-CT-2005-019015; HHMI(US) 55005624 Institutional research plan: CEZ:AV0Z50110509 Keywords : angiotensin-receptor blockers * cardiovascular protection * renin-angiotensin system Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.122, year: 2008

  11. Telmisartan/Hydrochlorothiazide combination therapy for the treatment of hypertension: a pooled analysis in older and younger patients.

    Science.gov (United States)

    Kjeldsen, Sverre E; Schumacher, Helmut; Neldam, Steen; Guthrie, Robert M

    2013-06-01

    Older patients frequently receive angiotensin II receptor blocker/diuretic combinations to control blood pressure (BP), although there have been relatively few trials specifically examining this patient population. A pooled analysis was performed of data from 7 randomized trials of telmisartan/hydrochlorothiazide combinations or telmisartan monotherapy in older (65 years and older) and younger (younger than 65 years) patients to better understand the response of older patients to a telmisartan/hydrochlorothiazide combination. Telmisartan doses were 40 mg and 80 mg (T40 and T80). Hydrochlorothiazide doses were 12.5 mg and 25 mg (H12.5 and H25). A total of 3654 patients were included and the mean treatment duration was approximately 8 weeks. BP reductions with telmisartan/hydrochlorothiazide combinations were broadly similar in older and younger patients. In older patients, mean BP reductions from baseline were -30.1/-19.0 mm Hg with the T80/H25 combination and -21.7/-13.0 mm Hg with T80 monotherapy. Tolerability was similar regardless of age, and the incidence of adverse events in both older and younger patients was similar to placebo. The telmisartan/hydrochlorothiazide combination, particularly high-dose T80/H25, is effective and well tolerated in patients 65 years and older as well as in younger patients. © 2013 Wiley Periodicals, Inc.

  12. Telmisartan Exerts Anti-Tumor Effects by Activating Peroxisome Proliferator-Activated Receptor-γ in Human Lung Adenocarcinoma A549 Cells

    Directory of Open Access Journals (Sweden)

    Juan Li

    2014-03-01

    Full Text Available Telmisartan, a member of the angiotensin II type 1 receptor blockers, is usually used for cardiovascular diseases. Recent studies have showed that telmisartan has the property of PPARγ activation. Meanwhile, PPARγ is essential for tumor proliferation, invasion and metastasis. In this work we explore whether telmisartan could exert anti-tumor effects through PPARγ activation in A549 cells. MTT and trypan blue exclusion assays were included to determine the survival rates and cell viabilities. RT-PCR and western blotting were used to analyze the expression of ICAM-1, MMP-9 and PPARγ. DNA binding activity of PPARγ was evaluated by EMSA. Our data showed that the survival rates and cell viabilities of A549 cells were all reduced by telmisartan in a time- and concentration-dependent manner. Meanwhile, our results also demonstrated that telmisartan dose-dependently inhibited the expression of ICAM-1 and MMP-9. Moreover, the cytotoxic and anti-proliferative effects, ICAM-1 and MMP-9 inhibitive properties of telmisartan were totally blunted by the PPARγ antagonist GW9662. Our findings also showed that the expression of PPARγ was up-regulated by telmisartan in a dose dependent manner. And, the EMSA results also figured out that DNA binding activity of PPARγ was dose-dependently increased by telmisartan. Additionally, our data also revealed that telmisartan-induced PPARγ activation was abrogated by GW9662. Taken together, our results indicated that telmisartan inhibited the expression of ICAM-1 and MMP-9 in A549 cells, very likely through the up-regulation of PPARγ synthesis.

  13. Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice

    Directory of Open Access Journals (Sweden)

    Shiota Asuka

    2012-11-01

    Full Text Available Abstract Background Telmisartan is a well-established angiotensin II type 1 receptor blocker that improves insulin sensitivity in animal models of obesity and insulin resistance, as well as in humans. Telmisartan has been reported to function as a partial agonist of the peroxisome proliferator-activated receptor (PPAR γ, which is also targeted by the nicotinamide adenine dinucleotide (NAD-dependent deacetylase (SIRT1. Here, we investigated the pathways through which telmisartan acts on skeletal muscle, in vitro as well as in vivo. Methods Nine-week-old male db/db mice were fed a 60% high-fat diet, with orally administrated either vehicle (carboxymethyl-cellulose, CMC, 5 mg/kg telmisartan, or 5 mg/kg telmisartan and 1 mg/kg GW9662, a selective irreversible antagonist of PPARγ, for 5 weeks. Effects of telmisartan on Sirt1 mRNA, AMPK phosphorylation, and NAD+/NADH ratio were determined in C2C12 cultured myocytes. Results and discussion Telmisartan treatment improved insulin sensitivity in obese db/db mice fed a high-fat diet and led to reduction in the size of hypertrophic pancreatic islets in these mice. Moreover, in vitro treatment with telmisartan led to increased expression of Sirt1 mRNA in C2C12 skeletal muscle cells; the increase in Sirt1 mRNA in telmisartan-treated C2C12 myoblasts occurred concomitantly with an increase in AMPK phosphorylation, an increase in NAD+/NADH ratio, and increases in the mRNA levels of PGC1α, FATP1, ACO, and GLUT4. Conclusions Our results indicate that telmisartan acts through a PPARγ-independent pathway, but at least partially exerts its effects by acting directly on skeletal muscle AMPK/SIRT1 pathways.

  14. Metabolic effect of combined telmisartan and nifedipine CR therapy in patients with essential hypertension

    Directory of Open Access Journals (Sweden)

    Shimizu Y

    2012-09-01

    Full Text Available Yuji Shimizu,1,4 Fumiyasu Yamasaki,4 Takashi Furuno,1,4 Toru Kubo,1 Takayuki Sato,3,4 Yoshinori Doi,1 Tetsuro Sugiura21Medicine and Geriatrics, 2Clinical Laboratory, 3Cardiovascular Control, Kochi Medical, School, Nankoku, Japan; 4Section of Cardiology, Inoue Hospital, Takaoka, JapanBackground: In addition to exerting a blood pressure (BP-lowering effect, telmisartan produces favorable metabolic effects via peroxisome proliferator-activated receptor γ activation. While a combination of telmisartan and a calcium channel blocker is often used to achieve a target BP level, the metabolic effects of this drug combination remain unclear. Therefore, this study evaluated the metabolic effects of telmisartan plus nifedipine controlled release (CR therapy, in hypertensive patients without metabolic disease.Methods: Sixteen patients with essential hypertension, who had not undergone antihypertensive therapy in the previous 6 months, were studied. Patients were initiated on telmisartan (40 mg/day. If their office BP was not reduced to 140/90 mmHg after 6 weeks, nifedipine CR (20–40 mg per day was added for 18 weeks. The other patients whose BP had achieved the target of 140/90 mmHg, continued only telmisartan.Results: Telmisartan reduced BP (174 ± 13/92 ± 10 to 143 ± 22/78 ± 11 mmHg; P < 0.01 at 6 weeks in 16 patients, but eight patients did not achieve target BP levels and required addition of nifedipine. Telmisartan also resulted in a reduction in the homeostatic model assessment of insulin resistance (HOMA-IR (1.30 ± 0.65 to 1.10 ± 0.42; P < 0.05 at 6 weeks, but did not affect adiponectin or leptin levels. Addition of nifedipine (n = 8 resulted in a reduction in BP (158 ± 18/80 ± 13 to 131 ± 8/73 ± 13 mmHg; P < 0.01 at 18 weeks, but did not affect the HOMA-IR (1.10 ± 0.40 to 1.02 ± 0.56; ns. In patients who did not require addition of nifedipine (n = 8, BP levels remained nearly identical at 18 weeks (127 ± 13/73 ± 9 to 128 ± 13/68 ± 8

  15. Beta Blockers

    Science.gov (United States)

    ... may not work as effectively for people of African heritage and older people, especially when taken without ... conditions/high-blood-pressure/in-depth/beta-blockers/ART-20044522 . Mayo Clinic Footer Legal Conditions and Terms ...

  16. Angiotensin-2-mediated Ca2+ signaling in the retinal pigment epithelium: role of angiotensin-receptor-associated-protein and TRPV2 channel.

    Directory of Open Access Journals (Sweden)

    Rene Barro-Soria

    Full Text Available Angiotensin II (AngII receptor (ATR is involved in pathologic local events such as neovascularisation and inflammation including in the brain and retina. The retinal pigment epithelium (RPE expresses ATR in its AT1R form, angiotensin-receptor-associated protein (Atrap, and transient-receptor-potential channel-V2 (TRPV2. AT1R and Atrap co-localize to the basolateral membrane of the RPE, as shown by immunostaining. Stimulation of porcine RPE (pRPE cells by AngII results in biphasic increases in intracellular free Ca(2+inhibited by losartan. Xestospongin C (xest C and U-73122, blockers of IP3R and PLC respectively, reduced AngII-evoked Ca(2+response. RPE cells from Atrap(-/- mice showed smaller AngII-evoked Ca(2+peak (by 22% and loss of sustained Ca(2+elevation compared to wild-type. The TRPV channel activator cannabidiol (CBD at 15 µM stimulates intracellular Ca(2+-rise suggesting that porcine RPE cells express TRPV2 channels. Further evidence supporting the functional expression of TRPV2 channels comes from experiments in which 100 µM SKF96365 (a TRPV channel inhibitor reduced the cannabidiol-induced Ca(2+-rise. Application of SKF96365 or reduction of TRPV2 expression by siRNA reduced the sustained phase of AngII-mediated Ca(2+transients by 53%. Thus systemic AngII, an effector of the local renin-angiotensin system stimulates biphasic Ca(2+transients in the RPE by releasing Ca(2+from cytosolic IP3-dependent stores and activating ATR/Atrap and TRPV2 channels to generate a sustained Ca(2+elevation.

  17. H2 blockers

    Science.gov (United States)

    Peptic ulcer disease - H2 blockers; PUD - H2 blockers; Gastroesophageal reflux - H2 blockers; GERD - H2 blockers ... provider about your symptoms. If you have a peptic ulcer, your provider may prescribe H2 blockers along with ...

  18. Effect of captopril and telmisartan on methotrexate-induced hepatotoxicity in rats: impact of oxidative stress, inflammation and apoptosis.

    Science.gov (United States)

    Kelleni, Mina T; Ibrahim, Salwa A; Abdelrahman, Aly M

    2016-06-01

    Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid drug whose efficacy is limited by its hepatotoxicity. The aim of this study was to investigate the possible protective role of captopril (100 mg/kg/day, p.o. for seven days), an angiotensin converting enzyme inhibitor, and telmisartan (10 mg/kg/day p.o. for seven days), an angiotensin II receptor blocker with peroxisome proliferative receptor gamma (PPARγ) agonism, in a model of MTX (single dose 20 mg/kg i.p. at the fifth day) induced hepatotoxicity in rats. Results of the present study revealed MTX-induced hepatotoxicity as demonstrated by increased level of liver enzymes and confirmed by histopathology. Pretreatment with captopril or telmisartan produced a significant hepatic protection manifested as a significant (p captopril/Telmisartan, if tolerated and not contraindicated, as preferable antihypertensive agents in patients receiving MTX in their chemotherapy protocols.

  19. Inhibition of angiotensin II-induced facilitation of sympathetic neurotransmission in the pithed rat: a comparison between losartan, irbesartan, telmisartan, and captopril

    NARCIS (Netherlands)

    Balt, J. C.; Mathy, M. J.; Pfaffendorf, M.; van Zwieten, P. A.

    2001-01-01

    Numerous studies have shown that angiotensin II enhances sympathetic nervous transmission. The objective of the present study was to quantify the inhibitory effect of the angiotensin II type 1 (AT1) receptor blockers losartan, irbesartan and telmisartan and the angiotensin converting enzyme (ACE)

  20. Effects of Calcium-Channel Blocker Benidipine-Based Combination Therapy on Cardiac Events - Subanalysis of the COPE Trial.

    Science.gov (United States)

    Umemoto, Seiji; Ogihara, Toshio; Matsuzaki, Masunori; Rakugi, Hiromi; Shimada, Kazuyuki; Kawana, Masatoshi; Kario, Kazuomi; Ohashi, Yasuo; Saruta, Takao

    2018-01-25

    The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial was conducted to compare the effects of regimens combining the dihydropyridine calcium-channel blocker benidipine with each of 3 secondary agent types (an angiotensin-receptor blocker (ARB), a β-blocker and a thiazide) in Japanese hypertensive outpatients who did not achieve target blood pressure (events among the 3 benidipine-based regimens.We observed a total of 50 cardiac events, 4.2 per 1000 person-years. The incidences of total cardiac events and each cardiac event were similarly low among the 3 treatment groups. Unadjusted and multi-adjusted hazard ratios for total cardiac events showed no significant difference among the 3 treatment groups. This subanalysis of the COPE trial demonstrated that blood pressure-lowering regimens combining benidipine with an ARB, β-blocker or thiazide diuretic were similarly effective for the prevention of cardiac events in Japanese hypertensive outpatients.

  1. Pre-injury beta blocker use does not affect the hyperdynamic response in older trauma patients

    Directory of Open Access Journals (Sweden)

    David C Evans

    2014-01-01

    Full Text Available Purpose: Trauma dogma dictates that the physiologic response to injury is blunted by beta-blockers and other cardiac medications. We sought to determine how the pre-injury cardiac medication profile influences admission physiology and post-injury outcomes. Materials and Methods: Trauma patients older than 45 evaluated at our center were retrospectively studied. Pre-injury medication profiles were evaluated for angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACE-I/ARB, beta-blockers, calcium channel blockers, amiodarone, or a combination of the above mentioned agents. Multivariable logistic regression or linear regression analyses were used to identify relationships between pre-injury medications, vital signs on presentation, post-injury complications, length of hospital stay, and mortality. Results: Records of 645 patients were reviewed (mean age 62.9 years, Injury Severity Score >10, 23%. Our analysis demonstrated no effect on systolic and diastolic blood pressures from beta-blocker, ACE-I/ARB, calcium channel blocker, and amiodarone use. The triple therapy (combined beta-blocker, calcium channel blocker, and ACE-I/ARB patient group had significantly lower heart rate than the no cardiac medication group. No other groups were statistically different for heart rate, systolic, and diastolic blood pressure. Conclusions: Pre-injury use of cardiac medication lowered heart rate in the triple-agent group (beta-blocker, calcium channel blocker, and ACEi/ARB when compared the no cardiac medication group. While most combinations of cardiac medications do not blunt the hyperdynamic response in trauma cases, patients on combined beta-blocker, calcium channel blocker, and ACE-I/ARB therapy had higher mortality and more in-hospital complications despite only mild attenuation of the hyperdynamic response.

  2. Efficacy and safety of two fixed-dose combinations of S-amlodipine and telmisartan (CKD-828 versus S-amlodipine monotherapy in patients with hypertension inadequately controlled using S-amlodipine monotherapy: an 8-week, multicenter, randomized, double-blind, Phase III clinical study

    Directory of Open Access Journals (Sweden)

    Ihm SH

    2016-11-01

    Full Text Available Sang-Hyun Ihm,1 Hui-Kyung Jeon,1 Tae-Joon Cha,2 Taek-Jong Hong,3 Sang-Hyun Kim,4 Nae-Hee Lee,5 Jung Han Yoon,6 Namsik Yoon,7 Kyung-Kuk Hwang,8 Sang-Ho Jo,9 Ho-Joong Youn1 1Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, Seoul, 2Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, 3Division of Cardiology, Department of Internal Medicine, Pusan National University Hospital, Busan, 4Division of Cardiology, Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine, Seoul, 5Department of Cardiology, Soonchunhyang University Hospital, Bucheon, 6Division of Cardiology, Wonju College of Medicine, Yonsei University, Wonju, 7Department of Cardiology, Chonnam National University Hospital, Gwangju, 8Department of Internal Medicine, Chungbuk National University, College of Medicine, Cheongju, 9Division of Cardiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea Purpose: To evaluate the blood pressure (BP lowering efficacy and safety of CKD-828, a fixed-dose combination of S-amlodipine (the more active isomer of amlodipine besylate, which is calcium channel blocker and telmisartan (long acting angiotensin receptor blocker, in patients with hypertension inadequately controlled with S-amlodipine monotherapy.Patients and methods: Eligible patients (N=187 who failed to respond after 4-week S-amlodipine 2.5 mg monotherapy (sitting diastolic blood pressure [sitDBP] ≥90 mmHg to receive CKD-828 2.5/40 mg (n=63, CKD-828 2.5/80 mg (n=63, or S-amlodipine 2.5 mg (n=61 for 8 weeks. The primary efficacy endpoint, mean sitDBP change from baseline to Week 8, was compared between the combination (CKD-828 2.5/40 mg and CKD-828 2.5/80 mg and S-amlodipine monotherapy groups. The safety was assessed based on adverse events, vital signs, and physical examination findings.Results: After the 8

  3. Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration

    Science.gov (United States)

    Pitcher, Alex; Emberson, Jonathan; Lacro, Ronald V.; Sleeper, Lynn A.; Stylianou, Mario; Mahony, Lynn; Pearson, Gail D.; Groenink, Maarten; Mulder, Barbara J.; Zwinderman, Aeilko H.; De Backer, Julie; De Paepe, Anne M.; Arbustini, Eloisa; Erdem, Guliz; Jin, Xu Yu; Flather, Marcus D.; Mullen, Michael J.; Child, Anne H.; Forteza, Alberto; Evangelista, Arturo; Chiu, Hsin-Hui; Wu, Mei-Hwan; Sandor, George; Bhatt, Ami B.; Creager, Mark A.; Devereux, Richard B.; Loeys, Bart; Forfar, J. Colin; Neubauer, Stefan; Watkins, Hugh; Boileau, Catherine; Jondeau, Guillaume; Dietz, Harry C.; Baigent, Colin

    2015-01-01

    Rationale A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. Design A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials). PMID:25965707

  4. Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration.

    Science.gov (United States)

    Pitcher, Alex; Emberson, Jonathan; Lacro, Ronald V; Sleeper, Lynn A; Stylianou, Mario; Mahony, Lynn; Pearson, Gail D; Groenink, Maarten; Mulder, Barbara J; Zwinderman, Aeilko H; De Backer, Julie; De Paepe, Anne M; Arbustini, Eloisa; Erdem, Guliz; Jin, Xu Yu; Flather, Marcus D; Mullen, Michael J; Child, Anne H; Forteza, Alberto; Evangelista, Arturo; Chiu, Hsin-Hui; Wu, Mei-Hwan; Sandor, George; Bhatt, Ami B; Creager, Mark A; Devereux, Richard B; Loeys, Bart; Forfar, J Colin; Neubauer, Stefan; Watkins, Hugh; Boileau, Catherine; Jondeau, Guillaume; Dietz, Harry C; Baigent, Colin

    2015-05-01

    A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials). Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Efficacy of renin-angiotensin system (RAS) blockers on cardiovascular and renal outcomes in patients with type 2 diabetes.

    Science.gov (United States)

    Cao, Zemin; Cooper, Mark E

    2012-08-01

    Cardiovascular disease is the predominant cause of morbidity in people with type 2 diabetes. Hypertension frequently coexists with diabetes and substantially increases the risk of developing end-organ damage. Controlling hypertension in patients with diabetes is therefore critical to reducing microvascular and macrovascular complications. Agents that block the renin-angiotensin system are increasingly used in patients with diabetes based on their cardiovascular and renoprotective effects, in addition to their direct effects on reducing blood pressure. Telmisartan, an angiotensin II receptor blocker (ARB), has a number of distinguishing pharmacological properties such as having the longest half-life and highest lipophilicity in its class. The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET(®)) trial showed that telmisartan reduces cardiovascular morbidity (including myocardial infarction and stroke) in subjects with a broad spectrum of cardiovascular risk factors, including type 2 diabetes. Telmisartan is the only ARB indicated for the reduction of cardiovascular morbidity in patients with diabetes and end-organ damage, as well as in patients without diabetes but with a history of coronary artery disease, peripheral artery disease, or previous stroke. Trials of telmisartan in patients with diabetes and varying degrees of nephropathy also suggest that this drug can slow the progression of renal disease, an effect that appears to be at least partly independent of reduction in blood pressure. Telmisartan is therefore an important therapeutic option for optimizing cardiovascular and renal protection in the type 2 diabetic population.

  6. An Angiotensin II Type 1 Receptor Blocker Prevents Renal Injury via Inhibition of the Notch Pathway in Ins2 Akita Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Masaya Koshizaka

    2012-01-01

    Full Text Available Recently, it has been reported that the Notch pathway is involved in the pathogenesis of diabetic nephropathy. In this study, we investigated the activation of the Notch pathway in Ins2 Akita diabetic mouse (Akita mouse and the effects of telmisartan, an angiotensin II type1 receptor blocker, on the Notch pathway. The intracellular domain of Notch1 (ICN1 is proteolytically cleaved from the cell plasma membrane in the course of Notch activation. The expression of ICN1 and its ligand, Jagged1, were increased in the glomeruli of Akita mice, especially in the podocytes. Administration of telmisartan significantly ameliorated the expression of ICN1 and Jagged1. Telmisartan inhibited the angiotensin II-induced increased expression of transforming growth factor β and vascular endothelial growth factor A which could directly activate the Notch signaling pathway in cultured podocytes. Our results indicate that the telmisartan prevents diabetic nephropathy through the inhibition of the Notch pathway.

  7. Critical appraisal and pooled analysis of telmisartan alone or in combination with hydrochlorothiazide for achieving blood pressure goals

    Directory of Open Access Journals (Sweden)

    Satoshi Morimoto

    2010-06-01

    Full Text Available Satoshi Morimoto, Nobuyuki Takahashi, Tatsuyori Morita, Kazunori Someya, Nagaoki Toyoda, Toshiji IwasakaSecond Department of Internal Medicine, Kansai Medical University 2-3-1, Shinmachi, Hirakata, Osaka 573-1191, JapanAbstract: Rigid control of blood pressure (BP is essential to prevent cardiovascular disease. However, only about 40% of hypertensive patients undergoing pharmacological intervention with a single agent achieve their BP goals in contemporary clinical practice. Combined therapy using currently available agents is effective in maximizing treatment outcome, although it raises medical costs and decreases the drug compliance rate. To overcome such negative consequences, a combination tablet containing an angiotensin II receptor blocker (ARB with a small dose of hydrochlorothiazide (HCTZ is now available on the international market, including Japan. This article briefly describes the unique properties of telmisartan, a highly selective ARB for the angiotensin II type 1 receptor, including its long-acting characteristics and recent prospective multicenter randomized clinical trials, followed by a description of a newly-introduced combination tablet in Japan, which contains telmisartan and HCTZ. This article also reviews its safety and efficacy based on currently available evidence. Finally, evidence comparing telmisartan/HCTZ with other combination therapies is presented.Keywords: angiotensin II receptor blocker, ARB, blood pressure, hypertension, diuretics, PPAR-γ

  8. How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

    2010-01-01

    An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time...... of heart failure diagnosis have similar prognosis.Treatment options for patients developing heart failure while already treated with ACE inhibitors/ARBs and beta-blockers are very limited if current heart failure guidelines are followed. In this review possible strategies are outlined and important areas...

  9. Telmisartan

    Science.gov (United States)

    ... that can be opened by peeling back the paper layer from the foil and pushing the tablet ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  10. Chronobiologically explored effects of Telmisartan.

    Science.gov (United States)

    Prikryl, Pavel; Cornélissen, Germaine; Neubauer, Jiri; Prikryl, Pavel; Karpisek, Zdenek; Watanabe, Yoshihiko; Otsuka, Kuniaki; Halberg, Franz

    2005-01-01

    Effects of Micardis (Telmisartan), alone or with low-dose aspirin, on blood pressure and other cardiovascular endpoints are examined in 20 patients with MESOR-hypertension in a crossover, double-blind, randomized study consisting of three stages, each lasting 7 days: I-placebo, II-Micardis, and III-Micardis with low-dose aspirin. Treatment was administered each day at a different circadian stage, upon awakening, and 3, 6, 9, 12, 15 and 18 hr after awakening. During each stage, the following variables were measured at 3-hr intervals during waking: systolic and diastolic blood pressure, heart rate, ejection fraction, intrarenal resistive index, acceleration time, and serum creatinine. Each data series was analyzed by single cosinor. Results were summarized by population-mean least squares spectra. At matched treatment times, the MESOR and circadian amplitude of each variable were compared among the three treatments by paired t-tests. A prominent circadian rhythm characterizes all variables. Micardis was associated not only with a lowering of blood pressure, but also with a reduction of the circadian blood pressure amplitude. The ejection fraction was increased, and the resistive index and acceleration time were decreased, the effect being more pronounced when low-dose aspirin was added to Micardis. Any circadian-stage dependent effect of Micardis, with or without low-dose aspirin, will require monitoring over spans longer than a single day for a given treatment administration time.

  11. Feasibility and Association of Neurohumoral Blocker Up-titration After Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Martens, Pieter; Verbrugge, Frederik H; Nijst, Petra; Bertrand, Philippe B; Dupont, Matthias; Tang, Wilson H; Mullens, Wilfried

    2017-08-01

    Cardiac resynchronization therapy (CRT) improves mortality and morbidity on top of optimal medical therapy in heart failure with reduced ejection fraction (HFrEF). This study aimed to elucidate the association between neurohumoral blocker up-titration after CRT implantation and clinical outcomes. Doses of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta-blockers were retrospectively evaluated in 650 consecutive CRT patients implanted from October 2008 to August 2015 and followed in a tertiary multidisciplinary CRT clinic. All 650 CRT patients were on a maximal tolerable dose of ACE-I/ARB and beta-blocker at the time of CRT implantation. However, further up-titration was successful in 45.4% for ACE-I/ARB and in 56.8% for beta-blocker after CRT-implantation. During a mean follow-up of 37 ± 22 months, a total of 139 events occurred for the combined end point of heart failure admission and all-cause mortality. Successful, versus unsuccessful, up-titration was associated with adjusted hazard ratios of 0.537 (95% confidence interval 0.316-0.913; P = .022) for ACE-I/ARB and 0.633 (0.406-0.988; P = .044) for beta-blocker on the combined end point heart failure admission and all-cause mortality. Patients in the up-titration group exhibited a similar risk for death or heart failure admission as patients treated with the maximal dose (ACE-I/ARB: P = .133; beta-blockers: P = .709). After CRT, a majority of patients are capable of tolerating higher dosages of neurohumoral blockers. Up-titration of neurohumoral blockers after CRT implantation is associated with improved clinical outcomes, similarly to patients treated with the guideline-recommended target dose at the time of CRT implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Local angiotensin II promotes adipogenic differentiation of human adipose tissue mesenchymal stem cells through type 2 angiotensin receptor

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    Veronika Y. Sysoeva

    2017-12-01

    Full Text Available Obesity is often associated with high systemic and local activity of renin-angiotensin system (RAS. Mesenchymal stem cells of adipose tissue are the main source of adipocytes. The aim of this study was to clarify how local RAS could control adipose differentiation of human adipose tissue derived mesenchymal stem cells (ADSCs. We examined the distribution of angiotensin receptor expressing cells in human adipose tissue and found that type 1 and type 2 receptors are co-expressed in its stromal compartment, which is known to contain mesenchymal stem cells. To study the expression of receptors specifically in ADSCs we have isolated them from adipose tissue. Up to 99% of cultured ADSCs expressed angiotensin II (AngII receptor type 1 (AT1. Using the analysis of Ca2+ mobilization in single cells we found that only 5.2 ± 2.7% of ADSCs specifically respond to serial Ang II applications via AT1 receptor and expressed this receptor constantly. This AT1const ADSCs subpopulation exhibited increased adipose competency, which was triggered by endogenous AngII. Inhibitory and expression analyses showed that AT1const ADSCs highly co-express AngII type 2 receptor (AT2, which was responsible for increased adipose competency of this ADSC subpopulation.

  13. Disposition and metabolism of [(14)C] Sacubitril/Valsartan (formerly LCZ696) an angiotensin receptor neprilysin inhibitor, in healthy subjects.

    Science.gov (United States)

    Flarakos, Jimmy; Du, Yancy; Bedman, Timothy; Al-Share, Qusai; Jordaan, Pierre; Chandra, Priya; Albrecht, Diego; Wang, Lai; Gu, Helen; Einolf, Heidi J; Huskey, Su-Er; Mangold, James B

    2016-11-01

    1. Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor (ARNI) providing simultaneous inhibition of neprilysin (neutral endopeptidase 24.11; NEP) and blockade of the angiotensin II type-1 (AT1) receptor. 2. Following oral administration, [(14)C]LCZ696 delivers systemic exposure to valsartan and AHU377 (sacubitril), which is rapidly metabolized to LBQ657 (M1), the biologically active neprilysin inhibitor. Peak sacubitril plasma concentrations were reached within 0.5-1 h. The mean terminal half-lives of sacubitril, LBQ657 and valsartan were ∼1.3, ∼12 and ∼21 h, respectively. 3. Renal excretion was the dominant route of elimination of radioactivity in human. Urine accounted for 51.7-67.8% and feces for 36.9 to 48.3 % of the total radioactivity. The majority of the drug was excreted as the active metabolite LBQ657 in urine and feces, total accounting for ∼85.5% of the total dose. 4. Based upon in vitro studies, the potential for LCZ696 to inhibit or induce cytochrome P450 (CYP) enzymes and cause CYP-mediated drug interactions clinically was found to be low.

  14. Pharmacokinetic drug-drug interaction assessment between LCZ696, an angiotensin receptor neprilysin inhibitor, and hydrochlorothiazide, amlodipine, or carvedilol.

    Science.gov (United States)

    Hsiao, Hsiu-Ling; Langenickel, Thomas Heiko; Greeley, Michael; Roberts, John; Zhou, Wei; Pal, Parasar; Rebello, Sam; Rajman, Iris; Sunkara, Gangadhar

    2015-11-01

    LCZ696 is a first-in-class angiotensin receptor neprilysin inhibitor in development for treatments of hypertension and heart failure indications. In 3 separate studies, pharmacokinetic drug-drug interactions (DDIs) potential was assessed when LCZ696 was coadministered with hydrochlorothiazide (HCTZ), amlodipine, or carvedilol. The studies used a open-label, single-sequence, 3-period, crossover design in healthy subjects. Blood samples were collected to determine the pharmacokinetic parameters of LCZ696 analytes (AHU377, LBQ657, and valsartan), HCTZ, amlodipine, or carvedilol (R[+]- and S[-]-carvedilol) for statistical analysis. When coadministered LCZ696 with HCTZ, the 90% CIs of the geometric mean ratios of AUCtau,ss of HCTZ and that of LBQ657 were within a 0.80-1.25 interval, whereas HCTZ Cmax,ss decreased by 26%, LBQ657 Cmax,ss increased by 19%, and the AUCtau,ss and Cmax,ss of valsartan increased by 14% and 16%, respectively. Pharmacokinetics of amlodipine, R(+)- and S(-)-carvedilol, or LBQ657 were not altered after coadministration of LCZ696 with amlodipine or carvedilol. Coadministration of LCZ696 400 mg once daily (qd) with HCTZ 25 mg qd, amlodipine 10 mg qd, or carvedilol 25 mg twice a day (bid) had no clinically relevant pharmacokinetic drug-drug interactions. LCZ696, HCTZ, amlodipine, and carvedilol were safe and well tolerated when given alone or concomitantly in the investigated studies. © 2015, The American College of Clinical Pharmacology.

  15. Calcium Channel Blockers

    Science.gov (United States)

    ... conditions, such as Raynaud's disease For people of African heritage and older people, calcium channel blockers might ... high-blood-pressure/in-depth/calcium-channel-blockers/ART-20047605 . Mayo Clinic Footer Legal Conditions and Terms ...

  16. [Effect of tanshinone II A on angiotensin receptor in hypertrophic myocardium of rats with pressure over-loading].

    Science.gov (United States)

    Li, Yong-Sheng; Wang, Zhao-Hua; Wang, Jin

    2008-07-01

    To explore the molecular biological mechanism of tanshinone II A (TSN) in preventing hypertensive left ventricular hypertrophy (HLVH) through studying the effects of TSN on angiotensin receptor (ATR) expression and free calcium ion ([Ca2+]i) in rats with hypertrophic myocardium caused by abdominal aorta constriction. SD rats were established into HLVH model by abdominal aorta constriction operation, they were randomly divided into the model group, the three treated groups treated respectively with intra peritoneal injection of low dose TSN (10 mg/kg) and high dose TSN (20 mg/kg) and gastrogavage of Valsartan (10 mg/kg) once a day 4 weeks after modeling. Besides, 8 sham-operated SD rats were set up as the control group. Eight weeks later, rats' caudal arterial pressure was measured, and their hearts were taken for measuring the left ventricular mass index (LVMI) and myocardial fiber diameter (MFD) by HE stain of the pathological section. Moreover, the mRNA and protein expressions of AT1 and AT2 receptors in the left ventricular tissue were detected by RT-PCR and Western blot, and [Ca2+]i concentration was determined with laser-scanning confocal microscope. (1) The elevated blood pressure in the TSN treated groups, either high or low dose, remained unchanged, significantly higher than that in the control group and the Valsartan treated group (P 0.05). (5) The elevated (Ca2+]i concentration in hypertrophic myocardium after modeling was significantly lowered after treatment in the three treated groups (P TSN treated group was more significant than that in the Valsartan treated group (P TSN on myocardial hypertrophy is blood pressure independent, its mechanism is possibly related with the inhibition on AT1R gene expression and the blocking of free calcium ion influx in cardiac muscle cells. AT2 receptor may participate the effect of Valsartan in lowering blood pressure and reversing myocardial hypertrophy.

  17. Overexpression of ß-Arrestin1 in the Rostral Ventrolateral Medulla Downregulates Angiotensin Receptor and Lowers Blood Pressure in Hypertension.

    Science.gov (United States)

    Sun, Jia-Cen; Liu, Bing; Zhang, Ru-Wen; Jiao, Pei-Lei; Tan, Xing; Wang, Yang-Kai; Wang, Wei-Zhong

    2018-01-01

    Background: Hypertension is characterized by sympathetic overactivity, which is associated with an enhancement in angiotensin receptor type I (AT1R) in the rostral ventrolateral medulla (RVLM). β-arrestin1, a canonical scaffold protein, has been suggested to show a negative effect on G protein-coupled receptors via its internalization and desensitization and/or the biased signaling pathway. The major objectives of the present study were to observe the effect of β-arrestin1 overexpression in the RVLM on cardiovascular regulation in spontaneously hypertensive rats (SHR), and further determine the effect of β-arrestin1 on AT1R expression in the RVLM. Methods: The animal model of β-arrestin1 overexpression was induced by bilateral injection of adeno-associated virus containing Arrb1 gene (AAV-Arrb1) into the RVLM of WKY and SHR. Results: β-arrestin1 was expressed on the pre-sympathetic neurons in the RVLM, and its expression in the RVLM was significantly ( P Overexpression of β-arrestin1 in SHR significantly decreased baseline levels of blood pressure and renal sympathetic nerve activity, and attenuated cardiovascular effects induced by RVLM injection of angiotensin II (100 pmol). Furthermore, β-arrestin1 overexpression in the RVLM significantly reduced the expression of AT1R by 65% and NF-κB p65 phosphorylation by 66% in SHR. It was confirmed that β-arrestin1 overexpression in the RVLM led to an enhancement of interaction between β-arrestin1 and IκB-α. Conclusion: Overexpression of β-arrestin1 in the RVLM reduces BP and sympathetic outflow in hypertension, which may be associated with NFκB-mediated AT1R downregulation.

  18. Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat.

    Directory of Open Access Journals (Sweden)

    Irina Bogdarina

    2010-02-01

    Full Text Available Adverse events in pregnancy may 'programme' offspring for the later development of cardiovascular disease and hypertension. Previously, using a rodent model of programmed hypertension we have demonstrated the role of the renin-angiotensin system in this process. More recently we showed that a maternal low protein diet resulted in undermethylation of the At1b angiotensin receptor promoter and the early overexpression of this gene in the adrenal of offspring. Here, we investigate the hypothesis that maternal glucocorticoid modulates this effect on fetal DNA methylation and gene expression. We investigated whether treatment of rat dams with the 11beta-hydroxylase inhibitor metyrapone, could prevent the epigenetic and gene expression changes we observed. Offspring of mothers subjected to a low protein diet in pregnancy showed reduced adrenal Agtr1b methylation and increased adrenal gene expression as we observed previously. Treatment of mothers with metyrapone for the first 14 days of pregnancy reversed these changes and prevented the appearance of hypertension in the offspring at 4 weeks of age. As a control for non-specific effects of programmed hypertension we studied offspring of mothers treated with dexamethasone from day 15 of pregnancy and showed that, whilst they had raised blood pressure, they failed to show any evidence of Agtr1b methylation or increase in gene expression. We conclude that maternal glucocorticoid in early pregnancy may induce changes in methylation and expression of the Agtr1b gene as these are clearly reversed by an 11 beta-hydroxylase inhibitor. However in later pregnancy a converse effect with dexamethasone could not be demonstrated and this may reflect either an alternative mechanism of this glucocorticoid or a stage-specific influence.

  19. Cardiovascular Protective Effect of Metformin and Telmisartan: Reduction of PARP1 Activity via the AMPK-PARP1 Cascade.

    Directory of Open Access Journals (Sweden)

    Fenqing Shang

    Full Text Available Hyperglycemia and hypertension impair endothelial function in part through oxidative stress-activated poly (ADP-ribose polymerase 1 (PARP1. Biguanides and angiotensin II receptor blockers (ARBs such as metformin and telmisartan have a vascular protective effect. We used cultured vascular endothelial cells (ECs, diabetic and hypertensive rodent models, and AMPKα2-knockout mice to investigate whether metformin and telmisartan have a beneficial effect on the endothelium via AMP-activated protein kinase (AMPK phosphorylation of PARP1 and thus inhibition of PARP1 activity. The results showed that metformin and telmisartan, but not glipizide and metoprolol, activated AMPK, which phosphorylated PARP1 Ser-177 in cultured ECs and the vascular wall of rodent models. Experiments using phosphorylated/de-phosphorylated PARP1 mutants show that AMPK phosphorylation of PARP1 leads to decreased PARP1 activity and attenuated protein poly(ADP-ribosylation (PARylation, but increased endothelial nitric oxide synthase (eNOS activity and silent mating type information regulation 2 homolog 1 (SIRT1 expression. Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.

  20. Effects of Telmisartan with Hydrochlorothiazide versus Valsartan with Hydrochlorothiazide in Patients with Moderate-to-Severe Hypertension

    Directory of Open Access Journals (Sweden)

    Ravi Marfatia

    2012-01-01

    Full Text Available Combination therapy is recommended for patients with blood pressure (BP significantly above goal by recent consensus guidelines around the globe. The use of angiotensin II receptor blockers (ARBs alone or in combination with a thiazide diuretic is a preferred treatment strategy due to both efficacy and safety considerations. However, there are few data known about the benefits of ARB-diuretic combination therapy in patients with moderate-to-severe hypertension. We performed a subanalysis from two large clinical trials that compared the antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg, both combined with hydrochlorothiazide (HCTZ 25 mg in a subpopulation of 725 patients with moderate-to-severe hypertension (systolic BP SBP ≥ 160 mm Hg. Treatment with telmisartan-HCTZ induced significantly greater reductions in BP (−31.1/−18.3 mm Hg than valsartan-HCTZ (−28.4/−16.3 mm Hg; SBP =0.0265, diastolic BP =0.0041. More patients receiving the telmisartan combination achieved a BP goal < 140/90 mm Hg than those receiving valsartan-HCTZ. There were similar safety and tolerability data for the two active treatment groups. These findings support the use of longer-acting ARBs combined with higher doses of thiazide diuretic to improve BP control in patients with moderate-to-severe hypertension.

  1. Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor.

    Science.gov (United States)

    Khallaf, Waleed A I; Messiha, Basim A S; Abo-Youssef, Amira M H; El-Sayed, Nesrine S

    2017-07-01

    Angiotensin II has pro-inflammatory and pro-oxidant potentials. We investigated the possible protective effects of the Angiotensin II receptor blocker telmisartan, compared with the superoxide scavenger tempol, on lipopolysaccharide (LPS)-induced cognitive decline and amyloidogenesis. Briefly, mice were allocated into a normal control group, an LPS control group, a tempol treatment group, and 2 telmisartan treatment groups. A behavioral study was conducted followed by a biochemical study via assessment of brain levels of beta amyloid (Aβ) and brain-derived neurotropic factor (BDNF) as amyloidogenesis and neuroplasticity markers, tumor necrosis factor alpha (TNF-α), nitric oxide end products (NOx), neuronal and inducible nitric oxide synthase (nNOS and iNOS) as inflammatory markers, and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using routine and special Congo red stains. Tempol and telmisartan improved cognition, decreased brain Aβ deposition and BDNF depletion, decreased TNF-α, NOx, nNOS, iNOS, MDA, and NT brain levels, and increased brain SOD and GSH contents, parallel to confirmatory histopathological evidences. In conclusion, tempol and telmisartan are promising drugs in managing cognitive impairment and amyloidogenesis, at least via upregulation of BDNF with inhibition of neuroinflammation and oxido-nitrosative stress.

  2. The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

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    Cornock Ruth

    2010-08-01

    Full Text Available Abstract Background Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR and vasopressin-related aquaporins (AQP, hypothesising that an alteration in the balance of these proteins would be associated with pregnancy per se and with compromised plasma volume expansion in rats fed a low-protein diet. Methods Female Wistar rats were mated and fed a control (18% casein or low-protein (9% casein diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle. Results As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT2R protein expression was observed in low-protein fed animals

  3. Pharmacokinetic interaction of telmisartan with s-amlodipine: an open-label, two-period crossover study in healthy Korean male volunteers.

    Science.gov (United States)

    Noh, Yook-Hwan; Lim, Hyeong-Seok; Kim, Mi Jo; Kim, Yo Han; Choi, Hee Youn; Sung, Hye Ryoung; Jin, Seok-Joon; Lim, Jonglae; Bae, Kyun-Seop

    2012-07-01

    Telmisartan belongs to a class of orally active angiotensin II receptor blockers (ARBs), and S-amlodipine is an enantiomer of amlodipine. Amlodipine is a racemic mixture and the calcium channel blocking (CCB) effect is confined to S-amlodipine, whereas R-amlodipine has a 1000-fold lower activity and no racemization occurs in vivo in human plasma. Combination therapy of ARBs with CCBs provides advantages for blood pressure control and vascular protection over monotherapy. To investigate the effects of coadministration of telmisartan and S-amlodipine on the steady-state pharmacokinetic properties of each drug as a drug-drug interaction study required before developing the fixed-dose combination agent. This study comprised 2 separate parts, A and B; each was a multiple-dose, open-label, 2-sequence, 2-period, crossover study in healthy male Korean volunteers. In part A, volunteers were administered 80 mg of telmisartan, either alone or with 5 mg of S-amlodipine. In part B, volunteers were administered 5 mg of S-amlodipine, either alone or with 80 mg of telmisartan. Blood samples were taken on days 9 and 37, following the final dose of each treatment, and at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours after administration in part A, and were taken at 0 (predose), 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, and 24 hours after administration in part B. Plasma concentrations were determined using LC-MS/MS. The pharmacokinetic properties of each drug after coadministration of telmisartan and S-amlodipine were compared with those of each drug administered alone. Tolerability was assessed using measurements of vital signs, clinical chemistry tests, and interviews. Fifty-six volunteers were enrolled (32 in part A and 24 in part B), and all completed except 4 volunteers (3 withdrawn in part A and 1 withdrawn in part B). The geometric mean ratios (GMRs) (90% CI) for the C(max,ss) and AUC(τ,ss) of telmisartan (with or without S-amlodipine) were 1.039 (0

  4. Beta-blockers

    DEFF Research Database (Denmark)

    Arboe, Bente; Ulrik, Charlotte Suppli

    2013-01-01

    Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma....

  5. Heart Failure Therapeutics on the Basis of a Biased Ligand of the Angiotensin-2 Type 1 Receptor Rationale and Design of the BLAST-AHF Study (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure)

    NARCIS (Netherlands)

    Felker, G. Michael; Butler, Javed; Collins, Sean P.; Cotter, Gad; Davison, Beth A.; Ezekowitz, Justin A.; Filippatos, Gerasimos; Levy, Phillip D.; Metra, Marco; Ponikowski, Piotr; Soergel, David G.; Teerlink, John R.; Violin, Jonathan D.; Voors, Adriaan A.; Pang, Peter S.

    The BLAST-AHF (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure) study is designed to test the efficacy and safety of TRV027, a novel biased ligand of the angiotensin-2 type 1 receptor, in patients with acute heart failure (AHF). AHF remains a major public health problem, and

  6. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Hideki, E-mail: hkimura@u-fukui.ac.jp [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Mikami, Daisuke; Kamiyama, Kazuko [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Sugimoto, Hidehiro [Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Kasuno, Kenji; Takahashi, Naoki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yoshida, Haruyoshi [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Division of Nephrology, Obama Municipal Hospital, Obama, Fukui (Japan); Iwano, Masayuki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)

    2014-11-14

    Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  7. Renin angiotensin system blockers-associated angioedema in the Thai population: analysis from Thai National Pharmacovigilance Database.

    Science.gov (United States)

    Win, Thet Su Zin; Chaiyakunapruk, Nathorn; Suwankesawong, Wimon; Dilokthornsakul, Piyameth; Nathisuwan, Surakit

    2015-09-01

    Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, co-morbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. A total of 895 cases were identified. Mean age was 59.9+12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4+13.9 vs 60.3+12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent.

  8. A review of the benefits of early treatment initiation with single-pill combinations of telmisartan with amlodipine or hydrochlorothiazide

    Directory of Open Access Journals (Sweden)

    Segura J

    2013-09-01

    Full Text Available Julian Segura, Luis Miguel Ruilope Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain Abstract: This review discusses the rationale for earlier use of single-pill combinations (SPCs of antihypertensive drugs, with a focus on telmisartan/amlodipine (T/A and telmisartan/hydrochlorothiazide (T/H SPCs. Compared with the respective monotherapies, the once-daily T/A and T/H SPCs have been shown to result in significantly higher blood pressure (BP reductions, BP goal rates, and response rates in patients at all stages of hypertension. As expected, BP reductions are highest with the highest dose (T80/A10 and T80/H25 SPCs. Subgroup analyses of the telmisartan trials have reported the efficacy of both SPCs to be consistent, regardless of the patients' age, race, and coexisting diabetes, obesity, or renal impairment. In patients with mild-to-moderate hypertension, the T/A combination provides superior 24-hour BP-lowering efficacy compared with either treatment administered as monotherapy. Similarly, the T/H SPC treatment provides superior 24-hour BP-lowering efficacy, especially in the last 6 hours relative to other renin–angiotensin system inhibitor-based SPCs. The T/A SPC is associated with a lower incidence of edema than amlodipine monotherapy, and the T/H SPC with a lower incidence of hypokalemia than hydrochlorothiazide monotherapy. Existing evidence supports the use of the T/A SPC for the treatment of hypertensive patients with prediabetes, diabetes, or metabolic syndrome, due to the metabolic neutrality of both component drugs, and the use of the T/H SPC for those patients with edema or in need of volume reduction. Keywords: calcium-channel blocker, essential hypertension, diuretic, primary care physician, renin-angiotensin system inhibitor

  9. Prevention and intervention studies with telmisartan, ramipril and their combination in different rat stroke models.

    Directory of Open Access Journals (Sweden)

    Christa Thoene-Reineke

    Full Text Available OBJECTIVES: The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats. METHODS: Prevention study: Stroke-prone spontaneously hypertensive rats (SHR-SP were subjected to high salt and randomly assigned to 4 groups: (1 untreated (NaCl, n = 24, (2 telmisartan (T; n = 27, (3 ramipril (R; n = 27 and (4 telmisartan + ramipril (T+R; n = 26. Drug doses were selected to keep blood pressure (BP at 150 mmHg in all groups. Neurological signs and stroke incidence at 50% mortality of untreated SHR-SP were investigated. Intervention study: Normotensive Wistar rats were treated s.c. 5 days prior to middle cerebral artery occlusion (MCAO for 90 min with reperfusion. Groups (n = 10 each: (1 sham, (2 vehicle (V; 0.9% NaCl, (3 T (0.5 mg/kg once daily, (4 R (0.01 mg/kg twice daily, (5 R (0.1 mg/kg twice daily or (6 T (0.5 mg/kg once daily plus R (0.01 mg/kg twice daily. Twenty-four and 48 h after MCAO, neurological outcome (NO was determined. Forty-eight h after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and neurotrophin receptor (TrkB were analysed. RESULTS: Stroke incidence was reduced, survival was prolonged and neurological outcome was improved in all treated SHR-SP with no differences between treated groups. In the acute intervention study, T and T+R, but not R alone, improved NO, reduced infarct volume, inflammation (TNFα, and induced TrkB receptor and neuronal survival in comparison to V. CONCLUSIONS: T, R or T+R had similar beneficial effects on stroke incidence and NO in hypertensive rats, confirming BP reduction as determinant factor in stroke prevention. In contrast, T and T+R provided superior neuroprotection in comparison to R alone in normotensive rats with induced cerebral ischemia.

  10. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2005-04-01

    Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

  11. Role of central angiotensin receptors in scopolamine-induced impairment in memory, cerebral blood flow, and cholinergic function.

    Science.gov (United States)

    Tota, Santoshkumar; Hanif, Kashif; Kamat, Pradeep Kumar; Najmi, Abul Kalam; Nath, Chandishwar

    2012-07-01

    Inhibition of renin-angiotensin system (RAS) improves cognitive functions in hypertensive patients. However, role of AT1 and AT2 receptors in memory impairment due to cholinergic hypofunction is unexplored. This study investigated the role of AT1 and AT2 receptors in cerebral blood flow (CBF), cholinergic neurotransmission, and cerebral energy metabolism in scopolamine-induced amnesic mice. Scopolamine was given to male Swiss albino mice to induce memory impairment tested in passive avoidance and Morris water maze tests after a week long administration of blocker of AT1 receptor, candesartan, and AT2 receptor, PD123, 319. CBF was measured by laser Doppler flowmetry. Biochemical and molecular studies were done in cortex and hippocampus of mice brain. Scopolamine caused memory impairment, reduced CBF, acetylcholine (ACh) level, elevated acetylcholinesterase (AChE) activity, and malondialdehyde (MDA). Administration of vehicle had no significant effect on any parameter in comparison to control. Candesartan prevented scopolamine-induced amnesia, restored CBF and ACh level, and decreased AChE activity and MDA level. In contrast, PD123, 319 was not effective. However, the effect of AT1 receptor blocker on memory, CBF, ACh level, and oxidative stress was blunted by concomitant blockade of AT2 receptor. Angiotensin-converting enzyme (ACE) activity, ATP level, and mRNA expression of AT1, AT2, and ACE remained unaltered. The study suggests that activation of AT1 receptors appears to be involved in the scopolamine-induced amnesia and that AT2 receptors contribute to the beneficial effects of candesartan. Theses finding corroborated the number of clinical studies that RAS inhibition in hypertensive patients could be neuroprotective.

  12. Calcium channel blocker overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this ... vary. However, the main ingredient is called a calcium-channel antagonist. It helps decrease the heart's pumping strength, which ...

  13. Impact of taurine supplementation on blood pressure in gestational protein-restricted offspring: Effect on the medial solitary tract nucleus cell numbers, angiotensin receptors, and renal sodium handling.

    Science.gov (United States)

    Scabora, José Eduardo; de Lima, Marcelo Cardoso; Lopes, Agnes; de Lima, Ize Penhas; Mesquita, Flávia Fernandes; Torres, Daniele Bráz; Boer, Patrícia Aline; Gontijo, José Antonio Rocha

    2015-03-01

    The current study considers changes of the postnatal brainstem cell number and angiotensin receptors by maternal protein restriction (LP) and LP taurine supplementation (LPT), and its impact on arterial hypertension development in adult life. The brain tissue studies were performed by immunoblotting, immunohistochemistry, and isotropic fractionator analysis. The current study shows that elevated blood pressure associated with decreased fractional urinary sodium excretion (FENa) in adult LP offspring was reverted by diet taurine supplementation. Also, that 12-day-old LP pups present a reduction of 21% of brainstem neuron counts, and, immunohistochemistry demonstrates a decreased expression of type 1 angiotensin II receptors (AT1R) in the entire medial solitary tract nuclei (nTS) of 16-week-old LP rats compared to age-matched NP and LPT offspring. Conversely, the immunostained type 2 AngII (AT2R) receptors in 16-week-old LP nTS were unchanged. The present investigation shows a decreased FENa that occurs despite unchanged creatinine clearance. It is plausible to hypothesize an association of decreased postnatal nTS cell number, AT1R/AT2R ratio and FENa with the higher blood pressure levels found in taurine-deficient progeny (LP) compared with age-matched NP and LPT offspring. © The Author(s) 2013.

  14. Meta-analysis of combined therapy with angiotensin receptor antagonists versus ACE inhibitors alone in patients with heart failure.

    Directory of Open Access Journals (Sweden)

    Andrea Kuenzli

    Full Text Available BACKGROUND: There is insufficient evidence whether the benefit of adding angiotensin II receptor blockers (ARBs to angiotensin-converting enzyme (ACE inhibitors outweighs the increased risk of adverse effects in patients with heart failure. METHODOLOGY/PRINCIPAL FINDINGS: Two independent reviewers searched and abstracted randomized controlled trials of ARBs and ACE inhibitors compared to ACE inhibitor therapy alone in patients with heart failure reporting mortality and hospitalizations having a follow-up of at least 6 months identified by a systematic literature search. Eight trials including a total of 18,061 patients fulfilled our inclusion criteria. There was no difference between patients treated with combination therapy and ACE inhibitor therapy alone for overall mortality, hospitalization for any reason, fatal or nonfatal MI. Combination therapy was, however, associated with fewer hospital admissions for heart failure (RR 0.81, 95%CI 0.72-0.91, although there was significant heterogeneity across trials (p-value for heterogeneity = 0.04; I(2 = 57% [95%CI 0-83%]. Patients treated with combination therapy had a higher risk of worsening renal function and symptomatic hypotension, and their trial medications were more often permanently discontinued. Lack of individual patient data precluded the analysis of time-to-event data and identification of subgroups which potentially benefit more from combination therapy such as younger patients with preserved renal function and thus at lower risk to experience worsening renal function or hyperkalemia. CONCLUSIONS/SIGNIFICANCE: Combination therapy with ARBs and ACE inhibitors reduces admissions for heart failure in patients with congestive heart failure when compared to ACE inhibitor therapy alone, but does not reduce overall mortality or all-cause hospitalization and is associated with more adverse events. Thus, based on current evidence, combination therapy with ARBs and ACE inhibitors may be reserved

  15. Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Garrido-Gil Pablo

    2012-02-01

    Full Text Available Abstract Background Several recent studies have shown that angiotensin type 1 receptor (AT1 antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ. PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions. Methods We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662. Results We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co

  16. Telmisartan as Monotherapy or add-on Therapy in African ...

    African Journals Online (AJOL)

    This study was conducted to evaluate the antihypertensive effect, tolerability and safety profile of telmisartan, an angiotensin II-receptor antagonist, when given alone or as add- on therapy to adult African subjects with mild to moderate essential hypertension for a period of 12- 48 weeks. Methods: This study was part of a ...

  17. Guideline-recommended therapy, including beta-blocker utilization, in patients with chronic heart failure: results from a Canadian community hospital heart function clinic

    Directory of Open Access Journals (Sweden)

    Heffernan M

    2016-06-01

    Full Text Available Michael Heffernan Division of Cardiology, Oakville Trafalgar Memorial Hospital, Oakville, ON, Canada Abstract: A comprehensive analysis of beta-blocker utilization and other guideline-recommended therapies for the treatment of chronic heart failure in a Canadian community hospital heart function clinic has not been undertaken and was, therefore, the focus of this study. The proportion of patients who would be potential candidates for ivabridine and sacubitril–valsartan therapy as a result of fulfilling the criteria for enrollment in either the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT study (left-ventricular ejection fraction [LVEF] >35%, sinus rhythm, New York Heart Association II–IV or the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI with angiotensin-converting enzyme inhibitor (ACEI to determine impact on global Mortality and Morbidity in Heart Failure (PARADIGM-HF study (LVEF <40%, New York Heart Association II–IV, glomerular filtration rate >30 mL/min, was also assessed. A retrospective cross-sectional analysis was carried out in all 371 patients treated in this community heart function clinic for at least a 12-month period. The patients were elderly (mean age 74±13.3 years and predominately male (61.5% with symptomatic (82.5% moderate left-ventricular dysfunction (LVEF 45.4%±15.6%. A substantial proportion of the patients also had a diagnosis of atrial fibrillation (52.8%. The total use of beta blockers exceeded 87%, while 100% of patients without a documented contraindication or intolerance to a beta blocker received therapy. Adherence to other guideline-recommended pharmacotherapies specifically for heart failure with reduced left ventricular ejection was high: 86.1% of the eligible patients were treated with an ACEI/angiotensin receptor blocker and 61.9% received a mineralcorticoid receptor antagonist. We determined that 13.7% of the complement of this heart

  18. Efficacy of Telmisartan Plus Amlodipine in Nonresponders to CCB Monotherapy

    Directory of Open Access Journals (Sweden)

    Steen Neldam

    2013-01-01

    Full Text Available Hypertensive patients unable to reach blood pressure (BP targets with antihypertensive monotherapy may be switched to a combination of two medications with complementary modes of action for improved treatment response. This post hoc analysis pools data from 2812 patients, 1891 of whom were not at goal (diastolic BP [DBP] <90 mm Hg with amlodipine 5 mg (A5 monotherapy who subsequently switched to telmisartan 40 or 80 mg (T80/A5 single-pill combination (SPC or amlodipine 10 mg (A10 monotherapy, and considers an additional 921 patients, 616 of whom were not at goal with A10 monotherapy who switched to telmisartan/amlodipine SPC. Patients switched to telmisartan/amlodipine SPC achieved significantly greater BP reductions compared with continued monotherapy (P<0.0001 with reductions of −15.2/−10.9 mm Hg seen with T80/A5 after 8 weeks in patients switched from A5. BP goal (<140/90 mm Hg, systolic BP goal (<140 mm Hg, and DBP goal (<90 mm Hg were reached by significantly more patients with telmisartan/amlodipine than with monotherapy (P<0.0001 for all comparisons; 56.1%, 69.7%, and 66.9%, resp., in patients who switched from A5 to T80/A5. Early use of such combination therapy should be considered to quickly reach BP targets, particularly in patients with added risk.

  19. Determination of telmisartan in human blood plasma: Part I: Immunoassay development

    NARCIS (Netherlands)

    Hempen, C.M.; Gläsle-Schwarz, Liane; Kunz, Ulrich; Karst, U.

    2006-01-01

    Telmisartan is an angiotensin II receptor antagonist and a known drug against high blood pressure. In this report, the development of a new and rapid analytical technique, an enzyme-linked immunosorbent assay (ELISA) for the determination of telmisartan in human blood plasma is described. The

  20. Can Beta Blockers Cause Weight Gain?

    Science.gov (United States)

    Beta blockers: Do they cause weight gain? Can beta blockers cause weight gain? Answers from Sheldon G. ... can occur as a side effect of some beta blockers, especially the older ones, such as atenolol ( ...

  1. Effect of dietary fiber on the level of free angiotensin II receptor blocker in vitro.

    Science.gov (United States)

    Iwazaki, Ayano; Takahashi, Kazuhiro; Tamezane, Yui; Tanaka, Kenta; Nakagawa, Minami; Imai, Kimie; Nakanishi, Kunio

    2014-01-01

    The interaction between angiotensin II type 1 (AT1) receptor blockers (ARBs), such as losartan potassium (LO), candesartan (CA), and telmisartan (TE), and dietary fiber was studied as to the level of free ARB in vitro. When ARB was incubated with soluble (sodium alginate, pectin, and glucomannan) or insoluble (cellulose and chitosan) dietary fiber, the levels of free LO, TE, and CA decreased. This resulted only from mixing the dietary fiber with the ARBs and differed among the types of dietary fiber, and the pH and electrolytes in the mixture. The levels of free LO and TE tended to decrease with a higher concentration of sodium chloride in pH 1.2 fluid. These results suggest that it is important to pay attention to the possible interactions between ARBs and dietary fiber.

  2. initial angiotensin receptor blockade-induced decrease in albuminuria is associated with long-term renal outcome in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    Hellemons, Merel E; Persson, Frederik; Bakker, Stephan J L

    2011-01-01

    We aimed to investigate the individual impact of initial responses in urinary albumin excretion (UAE) and systolic blood pressure (SBP) to angiotensin II receptor blocker (ARB) treatment on long-term renal outcome in patients with type 2 diabetes and microalbuminuria....

  3. Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY

    Directory of Open Access Journals (Sweden)

    Takumi Hirata

    2013-01-01

    Full Text Available Aim. This study compared the effects of telmisartan and losartan on nonalcoholic fatty liver disease (NAFLD and biochemical markers of insulin resistance in hypertensive NAFLD patients with type 2 diabetes mellitus. Methods. This was a randomized, open-label, parallel-group comparison of therapy with telmisartan or losartan. Nineteen hypertensive NAFLD patients with type 2 diabetes were randomly assigned to receive telmisartan at a dose of 20 mg once a day (n=12 or losartan at a dose of 50 mg once a day (n=7 for 12 months. Body fat area as determined by CT scanning and hepatic fat content based on the liver-to-spleen (L/S ratio, as well as several parameters of glycemic and lipid metabolism, were compared before and after 12 months. Results. The telmisartan group showed a significant decline in serum free fatty acid (FFA level (from 0.87±0.26 to 0.59±0.22 mEq/L (mean ± SD, P=0.005 and a significant increase in L/S ratio (P=0.049 evaluated by CT scan, while these parameters were not changed in the losartan group. Conclusion. Although there was no significant difference in improvement in liver enzymes with telmisartan and losartan treatment in hypertensive NAFLD patients with type 2 diabetes after 12 months, it is suggested that telmisartan may exert beneficial effects by improving fatty liver.

  4. Corticosteroids decrease glomerular angiotensin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Douglas, J.G.

    1987-03-01

    Angiotensin II (ANG II) receptors of glomerular mesangial cells are regulated in vivo by changes in Na balance, effects that are presumed to be secondary to changes in circulating ANG II. However, since changes in ANG II were accompanied by parallel changes in plasma aldosterone in all models tested, it is possible that aldosterone may have also participated in the modulation of glomerular ANG II receptors. To test this hypothesis, short-term aldosterone infusions within the physiological range were employed to favor actions that would be mediated through a high-affinity mineralocorticoid receptor. The glucocorticoid, dexamethasone, was also tested to determine the mineralocorticoid specificity of the response. Two infusion rates were associated with a decrease in glomerular /sup 125/I ANG II receptor density of 33 and 45%, respectively. Serum potassium and urinary Na/K ratio were lower in the aldosterone group. Spironolactone abolished the effect of aldosterone consistent with an action mediated through a specific mineralocorticoid receptor. These studies support the hypothesis that corticosteroids modulate glomerular ANG II receptors and validate the complexity of glomerular receptor modulation. The downregulation observed would be expected to diminish the ability of ANG II to influence glomerular hemodynamics in models such as mineralocorticoid and glucocorticoid-induced hypertension.

  5. Effects of telmisartan and pioglitazone on high fructose induced metabolic syndrome in rats.

    Science.gov (United States)

    Shahataa, Mary Girgis; Mostafa-Hedeab, Gomaa; Ali, Esam Fouaad; Mahdi, Emad Ahmed; Mahmoud, Fatma Abd Elhaleem

    2016-08-01

    Metabolic syndrome (MS) is a cluster of hypertension, insulin resistance, dyslipidaemia, and hyperuricemia. This study was designed to assess the effect of telmisartan and pioglitazone on high fructose induced MS. Thirty-five male albino rats were classified into 5 groups: A, normal diet; B, high-fructose diet (HFD) subdivided into B1 (HFD only), B2 (telmisartan, 5 mg/kg), B3 (pioglitazone, 10 mg/kg), and B4 (telmisartan + pioglitazone). Administration of the drugs was started after the rats had been on HFD for 4 weeks and continued for 4 weeks. Body mass (BM), blood pressure (BP), uric acid (UA), total cholesterol, triglycerides (TG), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), blood urea nitrogen (BUN), creatinine, and nitric oxide (NO) were measured and the levels of fasting glucose and fasting insulin were estimated. Compared with group B1, telmisartan treatment significantly decreased BP, BM, serum glucose, insulin, UA, urea, cholesterol, TGA, and LDL and significantly increased HDL, whereas pioglitazone treatment significantly decreased BP, serum glucose, insulin, UA, urea, creatinine, cholesterol, TGA, and LDL and significantly increased HDL. Co-administration of pioglitazone + telmisartan significantly decreased insulin, urea, and creatinine compared with telmisartan alone. Combined telmisartan + pioglitazone allowed better control of BP, hyperglycaemia, insulin resistance, and the amelioration of BM increase that may be associated with pioglitazone treatment.

  6. Telmisartan prevents high-fat diet-induced hypertension and decreases perirenal fat in rats.

    Science.gov (United States)

    Wang, Yaping; Song, Yan; Suo, Meng; Jin, Xin; Tian, Gang

    2012-05-01

    We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the telmisartan group (n = 9) and the high-fat diet group (n = 10). The control group consisted of age-matched rats on a regular diet (n = 10). At the end of the treatment, the body weight, blood pressure, insulin sensitivity and serum adiponectin levels of all rats were examined, and their visceral fat was extracted and weighed. Our results showed that telmisartan improved insulin resistance and dyslipidemia and increased serum adiponectin levels. Telmisartan also lowered both systolic blood pressure and diastolic blood pressure, and decreased the accumulation of perirenal fat associated with high-fat diet. Furthermore, telmisartan increased adiponectin mRNA expression in the perirenal fat. Correlation analysis showed that both systolic blood pressure and diastolic blood pressure were positively correlated with perirenal fat. These effects of telmisartan may be mediated through decreases in perirenal fat and contributed to the improvement of perirenal fat function. Our findings suggested a strong link between perirenal fat and high-fat diet-induced hypertension, and identified telmisartan as a potential drug for the treatment of obesity-related hypertension.

  7. Effects of telmisartan on office and 24-hour ambulatory blood pressure: an observational study in hypertensive patients managed in primary care

    Directory of Open Access Journals (Sweden)

    Frederic Kontny

    2010-01-01

    Full Text Available Frederic Kontny1, Terje Risanger2, Arne Bye3, Øyvind Arnesen4, Odd Erik Johansen4 for the TELMIMORE Study Investigators51Dept of Cardiology, Volvat Medical Centre, Oslo, Norway; 2Prinsdal Health Centre, Oslo, Norway; 3Frosta Health Centre, Frosta, Norway; 4Medical Department, Boehringer-Ingelheim Norway KS, Asker, Norway; 5The TELMIMORE Study Investigators are listed at the end of the paperPurpose: Although elevated blood pressure (BP predicts future cardiovascular events, recommended BP targets often is not reached in the general community. In a clinical real-life setting we evaluated BP impact and tolerability of the angiotensin-II receptor blocker telmisartan in patients with essential hypertension.Patients and methods: Patients in this observational study not at target BP started or switched to telmisartan monotherapy (40 or 80 mg or a fixed-dose combination of telmisartan and hydrochlorothiazide (HCT 80 mg/12.5 mg. Office and 24-hour ambulatory BP (AMBP were measured before and after 8 weeks of treatment and physicians reported perceived drug efficacy and tolerability as “Very good”, “Good”, “Moderate” or “Bad”.Results: 100 patients (34% female, 60 years, BMI 29.4 kg/m2, mean office BP 159/92 mmHg of whom 38% were treatment naïve and 30%, 17%, 9% and 6% respectively were on 1, 2, 3 or 4 BP-lowering drugs, completed 8 weeks of treatment. The proportion of patients with office BP < 140/90 mmHg increased from 3% to 54% for systolic (P < 0.001, 38% to 75% for diastolic (P < 0.001, and 2% to 45% for systolic and diastolic BP (P < 0.001. A significant effect on BP levels was seen in patients being either treatment naïve or on 1 to 3 BP-lowering drugs at study entry, whereas no BP improvement occurred in those who switched from 4 drugs. Overall, mean 24-hour AMBP was reduced from 141/85 to 131/79 mmHg (P < 0.001. Drug efficacy and tolerability were perceived as “Very good” or “Good” by 44%/34% and 66%/27%, respectively

  8. Is the fixed-dose combination of telmisartan and hydrochlorothiazide a good approach to treat hypertension?

    Directory of Open Access Journals (Sweden)

    Marc P Maillard

    2007-07-01

    Full Text Available Marc P Maillard, Michel BurnierService of Nephrology, Department of Internal Medicine, Lausanne University Hospital, SwitzerlandAbstract: Blockade of the renin-angiotensin system with selective AT1 receptor antagonists is recognized as an effective mean to lower blood pressure in hypertensive patients. Among the class of AT1 receptor antagonists, telmisartan offers the advantage of a very long half-life. This enables blood pressure control over 24 hours using once-daily administration. The combination of telmisartan with hydrochlorothiazide is a logical step because numerous previous studies have demonstrated that sodium depletion enhances the antihypertensive efficacy of drugs interfering with the activity of the renin-angiotensin system (RAS. In accordance with past experience using similar compounds blocking the RAS, several controlled studies have now demonstrated that the fixed-dose combination of telmisartan/hydrochlorothiazide is superior in lowering blood pressure than either telmisartan or hydrochlorothiazide alone. Of clinical interest also is the observation that the excellent clinical tolerance of the angiotensin II receptor antagonist is not affected by the association of the low-dose thiazide. Thus telmisartan/hydrochlorothiazide is an effective and well-tolerated antihypertensive combination. Finally, the development of fixed-dose combinations should improve drug adherence because of the one-pill-a-day regimen.Keywords: telmisartan, hydrochlorothiazide, fixed-dose combinations, antihypertensive agent, safety, compliance

  9. Pharmacokinetic-pharmacodynamic model of the antihypertensive interaction between telmisartan and hydrochlorothiazide in spontaneously hypertensive rats.

    Science.gov (United States)

    Hao, Kun; Chen, Yuancheng; Zhao, Xiaoping; Liu, Xiaoquan

    2014-08-01

    The goal of this study was to establish an integrated indirect response pharmacokinetic-pharmacodynamic model between telmisartan and hydrochlorothiazide to describe the antihypertensive interaction of these two drugs in spontaneously hypertensive rats. The blood pressure and plasma concentrations were measured by the tail-cuff test and high performance liquid chromatography-mass spectrometry, respectively, in spontaneously hypertensive rats. The current pharmacokinetic-pharmacodynamic model was based on the non-competitive pharmacodynamic interaction of two drugs acting on different physiological processes. This model was able to acquire the temporal changes in drug concentration and blood pressure after administration of telmisartan or hydrochlorothiazide. The noncompetitive pharmacodynamic interaction assumed that the decreased blood pressure was attributed to the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after administration of these two drugs. There was no significant pharmacokinetic change of telmisartan and hydrochlorothiazide in the different groups tested. The model predicted a synergistic pharmacodynamic interaction when telmisartan was administered in combination with hydrochlorothiazide, which was notably stronger than if the effects were additive. The results showed that the presented pharmacokinetic-pharmacodynamic model was suitable for describing the antihypertensive interaction between telmisartan and hydrochlorothiazide. © 2014 Royal Pharmaceutical Society.

  10. How Do Beta Blocker Drugs Affect Exercise?

    Science.gov (United States)

    ... Aneurysm More How do beta blocker drugs affect exercise? Updated:Aug 22,2017 Beta blockers are a ... about them: Do they affect your ability to exercise? The answer can vary a great deal, depending ...

  11. Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers.

    Science.gov (United States)

    Heerspink, H J L; Johnsson, E; Gause-Nilsson, I; Cain, V A; Sjöström, C D

    2016-06-01

    To characterize the effect of dapagliflozin on albuminuria and estimated glomerular filtration rate (eGFR) and to determine whether effects on albuminuria were mediated through changes in glycated haemoblogin (HbA1c), systolic blood pressure (SBP), body weight or eGFR. We conducted a post hoc analysis of data pooled from two phase III clinical trials in hypertensive patients with type 2 diabetes (T2DM) on stable angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, randomly assigned to dapagliflozin 10 mg/day or matched placebo. This analysis included only patients with microalbuminuria or macroalbuminuria at baseline. Patients were randomized to receive dapagliflozin 10 mg (n = 167) or placebo (n = 189). Dapagliflozin resulted in greater 12-week reductions in albuminuria compared with placebo: -33.2% [95% confidence interval (CI) -45.4, -18.2]. The reduction in albuminuria was also present after adjusting for age, sex and changes in HbA1c, SBP, body weight and eGFR: -23.5% (95% CI -37.6, -6.3). There was a decrease in eGFR with dapagliflozin versus placebo that was readily reversed 1 week after last dose. No serious renal-related adverse events were observed in any group. Dapagliflozin was effective in lowering albuminuria in patients with T2DM and hypertension using renin-angiotensin system blockade therapy. Reductions in albuminuria were still present after adjusting for changes in HbA1c, SBP, body weight and eGFR. Dapagliflozin-induced improvements in glycaemic control and reductions in SBP, coupled with other potentially beneficial renal effects, may lead to a reduced long-term renal and cardiovascular risk. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  12. Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus.

    Science.gov (United States)

    Pena, Michelle J; Heinzel, Andreas; Rossing, Peter; Parving, Hans-Henrik; Dallmann, Guido; Rossing, Kasper; Andersen, Steen; Mayer, Bernd; Heerspink, Hiddo J L

    2016-07-05

    Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria. Liquid chromatography-tandem mass spectrometry metabolomics was performed on serum samples. Data from patients with type 2 diabetes and microalbuminuria (n = 49) treated with irbesartan 300 mg/day were used for discovery. LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally validated in patients with type 1 diabetes and macroalbuminuria (n = 50) treated with losartan 100 mg/day. Molecular process analysis was performed to link metabolites to molecular mechanisms contributing to ARB response. In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1-Q3: -69 to -8]. The classifier, consisting of 21 metabolites, was significantly associated with UAE response to irbesartan (p R(2) increase from 0.10 to 0.70; p R(2) increase from 0.20 to 0.59; p < 0.001). Specifically ADMA impacting eNOS activity appears to be a relevant factor in ARB response. A serum metabolite classifier was discovered and externally validated to significantly improve prediction of albuminuria response to ARBs in diabetes mellitus.

  13. Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects.

    Science.gov (United States)

    Kang, Woo Youl; Seong, Sook Jin; Ohk, Boram; Gwon, Mi-Ri; Kim, Bo Kyung; La, Sookie; Kim, Hyun-Ju; Cho, Seungil; Yoon, Young-Ran; Yang, Dong Heon; Lee, Hae Won

    2018-01-01

    A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (C max ) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC 0-t ) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean C max and AUC 0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan C max and AUC 0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine C max and AUC 0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the C max for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. CKD-828 FDC tablets were shown to

  14. Pharmacokinetics of acetaminophen and ibuprofen when coadministered with telmisartan in healthy volunteers.

    Science.gov (United States)

    Stangier, J; Su, C A; Fraunhofer, A; Tetzloff, W

    2000-12-01

    Two open-label, two-way, crossover studies were performed to assess any pharmacokinetic interaction of telmisartan with either acetaminophen or ibuprofen. Healthy male adult volunteers (n = 12) received a single oral dose of acetaminophen 1 g alone and with oral telmisartan 120 mg in one study. Oral ibuprofen 400 mg three times daily with and without oral once-daily telmisartan 120 mg was given for 7 days in the other study conducted in 6 males and 6 females. In both studies, there was a washout period of > or = 13 days between single and combination medication administration. The primary end points Cmax and AUC were compared between combination (acetaminophen or ibuprofen + telmisartan) and single-agent medication (acetaminophen or ibuprofen). Pharmacokinetic drug interaction was assessed by analysis of variance (ANOVA) and calculation of 90% confidence intervals (CI) for treatment ratios using log-transformed parameters. Bioequivalence (i.e., lack of interaction) was concluded if the 90% CI of the ratios for both Cmax and AUC were within the acceptance limit of 0.80 to 1.25. Geometric mean Cmax values for acetaminophen and R-(-)- and S-(+)-ibuprofen enantiomers were similar with and without telmisartan coadministration (12.6 micrograms/mL vs. 14.1 micrograms/mL; 17.3 micrograms/mL vs. 16.7 micrograms/mL; 19.4 micrograms/mL vs. 19.5 micrograms/mL, respectively), and values for R-(-)- as well as S-(+)-ibuprofen were bioequivalent. Geometric mean AUC values for acetaminophen and R-(-)- and S-(+)-ibuprofen were also bioequivalent with and without telmisartan. The distribution and elimination parameters of both acetaminophen and ibuprofen were comparable in the presence or absence of telmisartan. The concomitant and single-agent medications were all well tolerated. In conclusion, the long half-life and excellent safety profile of telmisartan were unaffected by concurrent acetaminophen or ibuprofen medication; thus, once-daily dosing of telmisartan can be maintained

  15. Simultaneous determination of ramipril, ramiprilat and telmisartan in human plasma using liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Gupta, V K; Jain, Rajeev; Lukram, Ojitkumar; Agarwal, Shilpi; Dwivedi, Ashish

    2011-01-15

    A rapid and sensitive liquid chromatography tandem mass spectrometry method has been developed and validated for the simultaneous determination of ramipril, ramiprilat and telmisartan in human plasma. The solid-phase extraction technique was used for the extraction of ramipril, ramiprilat and telmisartan from human plasma. Trandolaprilat and hydrochlorothiazide were used as the internal standards (ISs). Chromatography was performed on a Hypurity C18, 5 μm, 50 mm × 4.6mm column, with the mobile phase consisting of ammonium acetate and acetonitrile (in a 20:80 ratio), followed by detection using mass spectrometry. The method involves a simple reversed isocratic chromatography condition and mass spectrometry detection, which enables detection at sub-nanogram levels. The method was validated and the lower limit of quantification for ramipril, ramiprilat and telmisartan was found to be 0.1 ng mL(-1), 0.1 ng mL(-1) and 2 ng mL(-1), respectively. The mean recovery for ramipril, ramiprilat and telmisartan ranged from 90.1 to 104.1%. This method increased the sensitivity and selectivity; resulting in high-throughput analysis of ramipril, ramiprilat and telmisartan using two different ISs in a single experiment for bioequivalence studies, with a chromatographic run time of 1.5 min only. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828 formulation and coadministered telmisartan and S-amlodipine in healthy subjects

    Directory of Open Access Journals (Sweden)

    Kang WY

    2018-03-01

    Full Text Available Woo Youl Kang,1,2,* Sook Jin Seong,1,* Boram Ohk,1,2 Mi-Ri Gwon,1,3 Bo Kyung Kim,1,2 Sookie La,4 Hyun-Ju Kim,3 Seungil Cho,1 Young-Ran Yoon,1,2 Dong Heon Yang,5 Hae Won Lee1 1Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea; 2Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea; 3Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea; 4Analytical Research Division, Biocore Co Ltd, Seoul, Republic of Korea; 5Division of Cardiology, Department of Internal Medicine, Kyungpook National University School of Medicine & Hospital, Daegu, Republic of Korea *These authors contributed equally to this work Purpose: A new fixed-dose combination (FDC formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828 has been developed to increase convenience (as only one tablet is required per day and improve treatment compliance.Methods: The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography–tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period.Results: Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax and the area under the plasma concentration–time curve from time 0 to the last measurement (AUC0–t values of telmisartan were 522.29 ng/mL and 2,475.16 ng⋅h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng⋅h/mL for the individual agents

  17. Calcium channel blockers and prostate cancer.

    Science.gov (United States)

    Loughlin, Kevin R

    2014-07-01

    The relationship between calcium channel blockers and prostate cancer has been an area of increased interest to investigators. Calcium channel blockers have been shown to influence cell proliferation, differentiation, and apoptosis. Clinically, the association between calcium channel blockers and the development of prostate cancer has been controversial. However, on a basic science level, there is evidence that calcium channel blockers induce cytotoxicity in androgen receptor positive cell lines and may offer an innovative strategy for the treatment of castration-resistant prostate cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Telmisartan prevents high-fat diet-induced hypertension and decreases perirenal fat in rats

    OpenAIRE

    Wang, Yaping; Song, Yan; Suo, Meng; Jin, Xin; Tian, Gang

    2012-01-01

    We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the telmisartan group (n = 9) and the high-fat diet group (n = 10). The control group consisted of age-matched rats on a regular diet (n = 10). At the end of the treatment, the body weight, blood pressure, insulin sensitivity and serum adiponectin levels of all rats were examined, and th...

  19. Telmisartan activates endothelial nitric oxide synthase via Ser1177 phosphorylation in vascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Masahiro Myojo

    Full Text Available Because endothelial nitric oxide synthase (eNOS has anti-inflammatory and anti-arteriosclerotic functions, it has been recognized as one of the key molecules essential for the homeostatic control of blood vessels other than relaxation of vascular tone. Here, we examined whether telmisartan modulates eNOS function through its pleiotropic effect. Administration of telmisartan to mice significantly increased the phosphorylation level of eNOS (Ser1177 in the aortic endothelium, but administration of valsartan had no effect. Similarly, telmisartan treatment of human umbilical vein endothelial cells significantly increased the phosphorylation levels of AMP-activated protein kinase (Thr172 and eNOS and the concentration of intracellular guanosine 3',5'-cyclic monophosphate (cGMP. Furthermore, pretreatment with a p38 mitogen-activated protein kinase (p38 MAPK inhibitor suppressed the increased phosphorylation level of eNOS and intracellular cGMP concentration. These data show that telmisartan increases eNOS activity through Ser1177 phosphorylation in vascular endothelial cells mainly via p38 MAPK signaling.

  20. Disparate effects of eplerenone, amlodipine and telmisartan on podocyte injury in aldosterone-infused rats

    NARCIS (Netherlands)

    Liang, Wei; Chen, Cheng; Shi, Jing; Ren, Zhilong; Hu, Fengqi; van Goor, Harry; Singhal, Pravin C.; Ding, Guohua

    Background. Several studies in patients with primary aldosteronism (PA) have suggested that aldosterone (ALD) is directly contributing to albuminuria. However, there are limited data pertaining to the direct role of ALD in (EPL), telmisartan (TEL) and amlodipine (AML) on ALD-induced renal structural

  1. Safety of telmisartan in patients with arterial hypertension - An open-label observational study

    NARCIS (Netherlands)

    Michel, Martin C.; Bohner, Herbert; Köster, Jürgen; Schäfers, Rafael; Heemann, Uwe

    2004-01-01

    Objective: To determine whether age, gender, concomitant disease and/or previous or present antihypertensive medication affect the safety or antihypertensive efficacy of telmisartan in the treatment of arterial hypertension. Study Design and Methods: In this large-scale, open-label postmarketing

  2. Comparative study of telmisartan with pioglitazone on insulin resistance in type 2 diabetic mice

    International Nuclear Information System (INIS)

    Khan, A.; Qayyum, A.; Khan, B.T.

    2017-01-01

    Objective: To evaluate and compare the effects of telmisartan and pioglitazone on peripheral insulin resistance in diabetic mice. Study Design: Randomized control trail. Place and Duration of Study: National Institute of Health, Islamabad and pharmacology dept, Army Medical College, from 17th March to 17th June 2014. Material and Methods: Twenty four BALB/c mice, both male and female, of 35 to 40 grams were used for this study. Animals were randomly divided into four groups. Two were taken as control groups, one was normal control and the other was diabetic control. Two were taken as interventional groups and received either pioglitazone or telmisartan for four weeks after induction of diabetes. Results: After treatment, pioglitazone reduced all the biochemical parameters significantly when compared with diabetic control. Negative correlation between glucose and insulin was changed into positive correlation (r-value, 0.92) with significant p-value (0.015) in pioglitazone treated group, while telmisartan only managed to convert a negative correlation between insulin and glucose into statistically non-significant positive. Conclusion: Telmisartan although reduces glucose levels and improves beta cell mass but the effect is statistically non-significant as compared to pioglitazone. In hypertensive type 2 diabetics a combination of these two drugs may help in reducing the dose of pioglitazone and consequently the cardiovascular adverse effects of pioglitazone. (author)

  3. Progression of Renal Insufficiency in Patients with Essential Hypertension Treated with Renin Angiotensin Aldosterone System Blockers: An Electrocardiographic Correlation

    Directory of Open Access Journals (Sweden)

    Luis Rodriguez-Padial

    2017-12-01

    Full Text Available Background: There is a frequent association between renal insufficiency and cardiovascular disease in patients with essential hypertension (HTN. The aim of this study was to analyze the relationship between ECG parameters and the progress of renal damage in patients with treated HTN. Methods: 109 patients with HTN had their microalbuminuria monitored over a 3-year time frame. During the last 3 months of follow-up, an ECG was recorded. Patients were divided into 3 groups according to the deterioration of their renal function: normoalbuminuria during the study period (normo–normo; n = 51; normoalbuminuria developing microalbuminuria (normo–micro; n = 29; and microalbuminuria at baseline (micro–micro; n = 29. Results: There were no differences in presence of left ventricular hypertrophy between the 3 groups. RV6/RV5 >1 was observed more frequently as renal function declined (p = 0.025. The 12-lead QRS-complex voltage-duration product was significantly increased in patients without microalbuminuria at baseline who went on to develop microalbuminuria (p = 0.006. Patients who developed microalbuminuria during follow-up, with positive Cornell voltage criteria, showed a lesser degree of progression of microalbuminuria when compared with the rest of the subgroups (p = 0.044. Furthermore, patients with microalbuminuria at baseline treated with angiotensin receptor blockers and diuretics, and positive Cornell voltage criteria, showed a higher degree of microalbuminuria compared to those with negative Cornell voltage criteria (p = 0.016. Conclusions: In patients with HTN, we identified some ECG parameters, which predict renal disease progression in patients with HTN, which may permit the identification of patients who are at risk of renal disease progression, despite optimal antihypertensive pharmacotherapy.

  4. Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients.

    Science.gov (United States)

    Slagman, Maartje C J; Waanders, Femke; Vogt, Liffert; Damman, Kevin; Hemmelder, Marc; Navis, Gerjan; Laverman, Gozewijn D

    2012-03-01

    Renin-angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both under- and overtitration of sodium targeting can easily occur. We evaluated whether N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of volume expansion, predicts the benefits of sodium targeting in CKD patients. In a cross-over randomized controlled trial, 33 non-diabetic CKD patients (proteinuria 3.8 ± 0.4 g/24 h, blood pressure 143/86 ± 3/2 mmHg, creatinine clearance 89 ± 5 mL/min) were treated during 6-week periods with placebo, angiotensin receptor blockade (ARB; losartan 100 mg/day) and ARB plus diuretics (losartan 100 mg/day plus hydrochlorothiazide 25 mg/day), combined with LS (93 ± 52 mmol Na(+)/24 h) and regular sodium diet (RS; 193 ± 62 mmol Na(+)/24 h, P diuretics and was normalized by ARB + diuretic + LS [39 (26-59) pg/mL, P = 0.65 versus controls]. NT-proBNP levels above the upper limit of normal (>125 pg/mL) predicted a larger reduction of blood pressure and proteinuria by LS and diuretics but not by ARB, during all steps of the titration regimen. Elevated NT-proBNP levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of sodium targeting, but not RAAS blockade, in proteinuric CKD patients. Importantly, this applies to the untreated condition, as well as to the subsequent treatment steps, consisting of RAAS blockade and even RAAS blockade combined with diuretics. NT-proBNP can be a useful tool to identify CKD patients in whom sodium targeting can improve blood pressure and proteinuria.

  5. Cost Effectiveness of the Angiotensin Receptor Neprilysin Inhibitor Sacubitril/Valsartan for Patients with Chronic Heart Failure and Reduced Ejection Fraction in the Netherlands: A Country Adaptation Analysis Under the Former and Current Dutch Pharmacoeconomic Guidelines.

    Science.gov (United States)

    Ramos, Isaac Corro; Versteegh, Matthijs M; de Boer, Rudolf A; Koenders, Jolanda M A; Linssen, Gerard C M; Meeder, Joan G; Rutten-van Mölken, Maureen P M H

    2017-12-01

    To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained. We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis. The incremental cost-effectiveness ratio obtained was €17,600 per quality-adjusted life-year (QALY) gained. This was robust to changes in most structural assumptions and across different subgroups of patients. Probability sensitivity analysis results showed that the probability that LCZ696 is cost-effective at a €50,000 per QALY threshold is 99.8%, with a population expected value of perfect information of €297,128. On including indirect medical costs of life-years gained, the incremental cost-effectiveness ratio was €26,491 per QALY gained, and LCZ696 was 99.46% cost effective at €50,000 per QALY, with a population expected value of perfect information of €2,849,647. LCZ696 is cost effective compared with enalapril under the former and current Dutch guidelines. However, the (monetary) consequences of making a wrong decision were considerably different in both scenarios. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  6. Telmisartan reduced cerebral edema by inhibiting NLRP3 inflammasome in mice with cold brain injury.

    Science.gov (United States)

    Wei, Xin; Hu, Chen-Chen; Zhang, Ya-Li; Yao, Shang-Long; Mao, Wei-Ke

    2016-08-01

    The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury (TBI) and the potential mechanisms related to the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) pyrin domain-containing 3 (NLRP3) inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier (BBB) integrity, the neurological function and histological injury were assessed, at the same time, the mRNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein (ASC) and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.

  7. Misperceptions About β-Blockers and Diuretics

    Science.gov (United States)

    Ubel, Peter A; Jepson, Christopher; Asch, David A

    2003-01-01

    BACKGROUND Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe β-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than β-blockers and diuretics. METHODS We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, β-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P diuretics were less effective and β-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of β-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines

  8. Pharmacokinetics of repeated oral doses of amlodipine and amlodipine plus telmisartan in healthy volunteers.

    Science.gov (United States)

    Stangier, J; Su, C A

    2000-12-01

    This open-label, crossover study was performed to establish if there is evidence for interaction between telmisartan, an angiotensin II antagonist, and amlodipine, a class II (dihydropyridine) calcium channel antagonist, on the basis of pharmacokinetics and safety. In a two-way crossover trial, 12 healthy Caucasian males were randomized to receive once daily for 9 days oral amlodipine 10 mg with or without oral telmisartan 120 mg. After a washout period of > or = 13 days, the subjects were switched to the other medication regimen. The geometric means of the primary pharmacokinetic parameters at steady state (day 9) for amlodipine when given alone were the following: maximum plasma concentration (Cmax) 17.7 ng/mL, area under the plasma concentration-time curve (AUC) 331 ng.h/mL, and renal clearance 39.5 mL/min, with 8% of the total amlodipine dose being excreted. When concomitant telmisartan was given, the respective values were 18.7 ng/mL, 352 ng.h/mL, and 43.0 mL/min, with 9.4% of the total amlodipine dose being excreted renally. The limits of the 90% confidence intervals (CIs) for the ratios of these steady-state parameters were 0.97 to 1.14 for Cmax and 0.98 to 1.16 for AUC; both were within the predefined reference range (0.8 to 1.25) for bioequivalence. The high intersubject variability in urinary amlodipine excretion resulted in bioequivalence not being demonstrated for renal clearance. Adverse effects were few, mild to moderate in intensity, and transient whether amlodipine was given alone or with telmisartan. Vital signs, except for blood pressure, and clinical laboratory values were unaffected by either medication. The findings of this study show that concomitant telmisartan and amlodipine may be administered as there is no clinically significant variation in primary pharmacokinetic parameters of amlodipine in the presence of telmisartan, and the safety of the combination is comparable to that of amlodipine alone.

  9. Telmisartan in daily clinical practice: Factors affecting efficacy in treatment of primary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Bergovac M

    2009-01-01

    Full Text Available Background: Telmisartan provides effective treatment of hypertension in a broad spectrum of patients. Aims: To evaluate factors affecting the efficacy of telmisartan in daily clinical practice. Setting and Design: Prospective practice-based 12-week uncontrolled cohort study. Materials and Methods: Consecutive incident/prevalent outpatients with mild to moderate essential hypertension were started on telmisartan 40 mg/day with optional up-titration to 80 mg/day in order to achieve seated systolic (SSBP and diastolic (SDBP blood pressure < 140/90 mm Hg. Intent-to-treat (ITT, N=282 and per protocol (PP, N=275 efficacy assessment was based on SSBP/SDBP reduction and delivered doses. Results: SSBP/SDBP decreased (165.2±13.1 / 98.3±6.7 mm Hg to 137.9±13.2 / 82.6±7.3 mm Hg, whilst telmisartan was up-titrated in 40.5% of patients during the study. Multivariate (practically identical ITT and PP analysis indicated poorer response in obese vs. non-obese patients: lesser SDBP reduction (by around 2.2-2.3 mm Hg, P < 0.05 with higher odds of dose up-titration (odds ratio, OR around 1.90, P < 0.05; and better response in: a patients started on telmisartan monotherapy than when added to a preexisting treatment: greater SSBP/SDBP reduction (by around 4.0 and 3.0 mm Hg, respectively, P < 0.05 with comparable odds of up-titration; b diabetics vs. non-diabetics: greater SDBP reduction (by around 3.6-3.7 mm Hg, P < 0.05 with comparable odds of up-titration; c men vs. women: slightly greater SDBP reduction (by around 1.2 mm Hg, 0.05 P < 0.1 with lower odds of up-titration (OR around 0.51, P < 0.05. Conclusion: Previous unsuccessful treatment, obesity, diabetes and gender should be considered in order to optimize the use of telmisartan for mild to moderate essential hypertension in daily clinical practice.

  10. β1-Adrenoceptor blocker aggravated ventricular arrhythmia.

    Science.gov (United States)

    Wang, Yan; Patel, Dimpi; Wang, Dao Wu; Yan, Jiang Tao; Hsia, Henry H; Liu, Hao; Zhao, Chun Xia; Zuo, Hou Juan; Wang, Dao Wen

    2013-11-01

    To assess the impact of β1 -adrenoceptor blockers (β1 -blocker) and isoprenaline on the incidence of idiopathic repetitive ventricular arrhythmia that apparently decreases with preprocedural anxiety. From January 2010 to July 2012, six patients were identified who had idiopathic ventricular arrhythmias that apparently decreased (by greater than 90%) with preprocedural anxiety. The number of ectopic ventricular beats per hour (VPH) was calculated from Holter or telemetry monitoring to assess the ectopic burden. The mean VPH of 24 hours from Holter before admission (VPH-m) was used as baseline (100%) for normalization. β1 -Blockers, isoprenaline, and/or aminophylline were administrated successively on the ward and catheter lab to evaluate their effects on the ventricular arrhythmias. Among 97 consecutive patients with idiopathic ventricular arrhythmias, six had reduction in normalized VPHs in the hour before the scheduled procedure time from (104.6 ± 4.6%) to (2.8 ± 1.6%) possibly due to preprocedural anxiety (P < 0.05), then increased to (97.9 ± 9.7%) during β1 -blocker administration (P < 0.05), then quickly reduced to (1.6 ± 1.0%) during subsequent isoprenaline infusion. Repeated β1 -blocker quickly counteracted the inhibitory effect of isoprenaline, and VPHs increased to (120.9 ± 2.4%) from (1.6 ± 1.0%; P < 0.05). Isoprenaline and β1 -blocker showed similar effects on the arrhythmias in catheter lab. In some patients with structurally normal heart and ventricular arrhythmias there is a marked reduction of arrhythmias associated with preprocedural anxiety. These patients exhibit a reproducible sequence of β1 -blocker aggravation and catecholamine inhibition of ventricular arrhythmias, including both repetitive ventricular premature beats and monomorphic ventricular tachycardia. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

  11. Tissue-Specific Peroxisome Proliferator Activated Receptor Gamma Expression and Metabolic Effects of Telmisartan

    Czech Academy of Sciences Publication Activity Database

    Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Landa, Vladimír; Kazdová, L.; Pravenec, Michal; Kurtz, T. W.

    2013-01-01

    Roč. 26, č. 6 (2013), s. 829-835 ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP303/10/0505; GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Institutional support: RVO:67985823 Keywords : telmisartan * metabolic effects * tissue-specific Pparg knockout mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.402, year: 2013

  12. Study of effect of variables on particle size of telmisartan nanosuspensions using box-Behnken design.

    Science.gov (United States)

    Rao, M R P; Bajaj, A

    2014-12-01

    Telmisartan, an orally active nonpeptide angiotensin II receptor antagonist is a BCS Class II drug having aqueous solubility of 9.9 µg/ml and hence oral bioavailability of 40%. The present study involved preparation of nanosuspensions by evaporative antisolvent precipitation technique to improve the saturation solubility and dissolution rate of telmisartan. Various stabilizers such as TPGS, PVPK 30, PEG 6000 were investigated of which TPGS was found to provide maximum decrease in particle size and accord greater stability to the nanosuspensions. Box-Behnken design was used to investigate the effect of independent variables like stabilizer concentration, time and speed of stirring on particle size of nanosuspensions. Pharmacodynamic studies using Goldblatt technique were undertaken to evaluate the effect of nano-sizing on the hypotensive effect of the drug. Concentration of TPGS and speed of rotation were found to play an important role in particle size of the nanosuspensions whereas time of stirring displayed an exponential relationship with particle size. Freeze dried nanocrystals obtained from nanosuspension of least particle size were found to have increased saturation solubility of telmisartan in different dissolution media. The reconstituted nanosuspension was found to reduce both systolic and diastolic blood pressure without affecting pulse pressure and heart rate. Statistical tools can be used to identify key process and formulation parameters which play a significant role in controlling the particle size in nanosuspensions. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Quality-by-design approach for the development of telmisartan potassium tablets.

    Science.gov (United States)

    Oh, Ga-Hui; Park, Jin-Hyun; Shin, Hye-Won; Kim, Joo-Eun; Park, Young-Joon

    2018-05-01

    A quality-by-design approach was adopted to develop telmisartan potassium (TP) tablets, which were bioequivalent with the commercially available Micardis ® (telmisartan free base) tablets. The dissolution pattern and impurity profile of TP tablets differed from those of Micardis ® tablets because telmisartan free base is poorly soluble in water. After identifying the quality target product profile and critical quality attributes (CQAs), drug dissolution, and impurities were predicted to be risky CQAs. To determine the exact range and cause of risks, we used the risk assessment (RA) tools, preliminary hazard analysis and failure mode and effect analysis to determine the parameters affecting drug dissolution, impurities, and formulation. The range of the design space was optimized using the face-centered central composite design among the design of experiment (DOE) methods. The binder, disintegrant, and kneading time in the wet granulation were identified as X values affecting Y values (disintegration, hardness, friability, dissolution, and impurities). After determining the design space with the desired Y values, the TP tablets were formulated and their dissolution pattern was compared with that of the reference tablet. The selected TP tablet formulated using design space showed a similar dissolution to that of Micardis ® tablets at pH 7.5. The QbD approach TP tablet was bioequivalent to Micardis ® tablets in beagle dogs.

  14. The pharmacological research of Tek-1 relevance to anti-neuroinflammation, a candidate compound based on Telmisartan

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    Yang Jianbo

    2015-01-01

    Full Text Available In this paper, BV-2 mouse small glial cell inflammation model induced by LPS is established. The experiment used 0.1-10 μM of telmisartan and Tek-1 to incubate with small glial cell and used telmisartan and Tek-1 to incubate with PPAR gamma special heterosexual antagonistic anti-agent GW9662. The article used ELISA method to dectect TNF-a effect on small glial cell for telmisartan and Tek-1. The article used real-time quantitative PCR method to dectect mRNA level expression effect of CD11b, CD16 and iNOS on small glial cell for telmisartan and Tek-1 and used Western Blot method to dectect MAPKs signal pathway and NF-κb signal turned guide pathway effect on small glial cell for telmisartan and Tek-1. Results show that Tek-1 had high affinity with AT1 receptor and inhibited intracellular calcium ion activation which can be for the AT1 receptor antagonists. Meanwhile, Tek-1 can partially activate PPAR gamma compared with full agonists of rosiglitazone.

  15. Polymorphism of ORM1 is associated with the pharmacokinetics of telmisartan.

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    Wang-Qing Chen

    Full Text Available The pharmacokinetics (PKs and pharmacodynamics (PDs of telmisartan varies among the individuals, and the main causes remain unknown. The aim of this study was to evaluate the impact of ORM1, as well as ABCC2, ABCB1, ABCG2 and SLCO1B3 polymorphisms, on the disposition of the drug and BP change after taking 40 mg telmisartan in 48 healthy Chinese males.A total of 48 healthy males were included in this trial. Every volunteer ingested a single dose of 40 mg telmisartan, and the plasma drug concentration and blood pressure (BP were measured up to 48 h.In this study, the area under the plasma concentration-time curve (AUC in the heterozygotes of ORM1 113AG was higher than that in the wild-type homozygotes, AUC(0-48 (113AA vs. 113AG, 1,549.18±859.84 ng·h/ml vs. 2,313.54±1,257.71 ng·h/ml, P = 0.033, AUC(0-∞ (113AA vs. 113AG, 1,753.13±1,060.60 ng·h/ml vs. 2,686.90±1,401.87 ng·h/ml, P = 0.016, and the change(% of the diastolic blood pressure (DBP from the baseline BP value also showed a significant difference between the ORM1 113AG and 113AA genotypes at 5 h after taking telmisartan (P = 0.026. This study also showed that the allele of ABCC2 C3972T would affected the disposition of telmsiartan and the DBP change significantly after taking the drug. However, the common SNPs of ABCG2 C421, ABCB1 C3435T, and SLCO1B3 T334G showed no impacts on the PKs of telmisartan or BP change(% in our trial.The ORM1 A113G polymorphism was associated with the PKs variability after taking telmsiartan, as well as ABCC2 C3972T. The heterozygotes of ORM1 113AG showed a larger AUC and a notable BP change(% from the baseline compared with the wild-type.Chinese Clinical Trial Registry ChiCTR-TNC-10000898.

  16. Renin-angiotensin-aldosterone system blockers for heart failure with reduced ejection fraction or left ventricular dysfunction: Network meta-analysis.

    Science.gov (United States)

    Xie, Wuxiang; Zheng, Fanfan; Song, Xiaoyu; Zhong, Baoliang; Yan, Li

    2016-02-15

    Renin-angiotensin-aldosterone system (RAAS) blockers are effective therapies for heart failure and reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVD). We aimed to assess the efficacy and safety of RAAS blockers in these patients. We searched MEDLINE, EMBASE, and Cochrane Library in May 2015. Twenty-one double-blind randomized controlled trials (RCTs) with 69,229 patients were included this network meta-analysis. Compared with placebo, an angiotensin receptor-neprilysin inhibitor (ARNI) had the highest probability of reducing all-cause mortality (odds ratio [OR]=0.67, 95% credible interval [CrI]: 0.48-0.86), followed by an aldosterone receptor antagonist (ARA, OR=0.74, 95% CrI: 0.62-0.88) and an angiotensin-converting enzyme inhibitor (ACEI, OR=0.80, 95% CrI: 0.71-0.89). The most efficacious therapy for preventing heart failure hospitalization was ARNI (OR=0.55, 95% CrI: 0.40-0.71), followed by combination therapy with an angiotensin II receptor blocker (ARB) plus an ACEI (OR=0.61, 95% CrI: 0.49-0.75), then an ACEI alone (OR=0.69, 95% CrI: 0.61-0.77). Sensitivity analysis restricted to nine RCTs with a high background use of ACEI and/or ARB (>80%) indicated that adding an ARA to current standard therapy significantly reduced mortality (OR=0.73, 95% CrI: 0.51-0.95) and hospitalization risk (OR=0.67, 95% CrI: 0.47-0.87), but did not significantly increase the discontinuation risk (OR=1.29, 95% CrI: 0.83-2.31). ARNI has the highest probability of being the most efficacious therapy for HFrEF in reducing death and hospitalization for heart failure. ARA has the most favorable benefit-risk profile as an adjunct to background ACEI and/or ARB therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on the risk of pneumonia and severe exacerbations in patients with COPD

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    Lai CC

    2018-03-01

    Full Text Available Chih-Cheng Lai,1 Ya-Hui Wang,2 Cheng-Yi Wang,3 Hao-Chien Wang,4 Chong-Jen Yu,4 Likwang Chen5 On behalf of the Taiwan Clinical Trial Consortium for Respiratory Diseases (TCORE 1Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan; 2Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 3Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 4Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; 5Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan Objectives: This study aimed to compare the effects of angiotensin-converting-enzyme inhibitors (ACEis and angiotensin receptor blockers (ARBs on the risk of pneumonia and severe exacerbations in patients with COPD.Patients and methods: All patients with COPD who used ACEis and ARBs for >90 days between 2000 and 2005 were recruited. Pairwise matching (1:1 of the ACEi and ARB groups resulted in two similar subgroups, with 6,226 patients in each. The primary outcomes were pneumonia and COPD exacerbations, and the secondary outcome was death.Results: During the follow-up period, the incidence of pneumonia was 7.20 per 100 person-years in the ACEi group and 5.89 per 100 person-years in the ARB group. The ACEi group had a higher risk of pneumonia (adjusted hazard ratio [aHR], 1.22; 95% CI, 1.15–1.29 than the ARB group. The incidence of severe exacerbations was 0.65 per person-year for the patients receiving ACEis and 0.52 per person-year for those receiving ARBs. The patients receiving ACEis had a higher risk of severe exacerbations (aHR, 1.19; 95% CI, 1.16–1.21 than those receiving ARBs. Similar trends were noted in terms of severe exacerbations requiring

  18. Cardiovascular risk reduction by reversing endothelial dysfunction: ARBs, ACE inhibitors,  or both? Expectations from The ONTARGET  Trial Programme

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    Luis Miguel  Ruilope

    2007-03-01

    Full Text Available Luis Miguel  Ruilope1, Josep Redón2, Roland Schmieder31Servicio de Nefrologia, Unidad de Hipertension Hospital, 12 de Octubre, Madrid, Spain; 2Department of Internal Medicine, Hospital Clinico University of Valencia, Valencia, Spain; 3Department of Nephrology and Hypertension, Friedrich-Alexander-Universitat, Erlangen-Nurnberg, GermanyAbstract: Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin–angiotensin system (RAS, has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB and/or angiotensin-converting enzyme (ACE inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET Programme is expected to provide the ultimate evidence of whether improved endothelial func tion translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade. Completion of ONTARGET is expected in 2008. Keywords: angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, endothelial dysfunction, ONTARGET, renin–angiotensin system, telmisartan

  19. The effects of telmisartan on the nuclear factor of activated T lymphocytes signalling pathway in hypertensive patients.

    Science.gov (United States)

    Huang, Sha-Sha; He, Si-Li; Zhang, Yuan-Ming

    2016-01-01

    Previous studies provide links between the nuclear factor of activated T lymphocytes (NFAT) signalling pathway and the development of hypertension. Our preliminary studies indicate that telmisartan can block Kv1.3 potassium channels and effectively inhibit potassium current densities, along with Kv1.3 mRNA and protein expression levels. This paper aims to investigate whether telmisartan has an inhibitory effect on the NFAT signalling pathway after activation and proliferation of peripheral blood T lymphocytes in Kazakh patients with essential hypertension (EH) from Xinjiang, China. T lymphocytes were isolated using the immunomagnetic cell sorting method (MACS). The mRNA expression of NFATc1, IL-6 and TNF-α was measured by quantitative polymerase chain reaction (qRT-PCR) and relative protein levels were evaluated by Western blot. T cell samples from 50 hypertensive Kazakh patients from Xinjiang were randomly divided into control, telmisartan, cyclosporin A (CsA), VIVIT, and 4-aminopytidine (4-AP) groups. Peripheral blood T lymphocytes were first activated and proliferated in vitro, then incubated for 48 h under different treatment conditions before determination of protein and mRNA expression of NFATc1, IL-6, and TNF-α by Western blot and qRT-PCR analyses, respectively. There were no significant differences in cardiovascular risk factors among the patients with samples assigned to the five groups (p > 0.05). Expression of NFATc1, IL-6, and TNF-α mRNA and protein was significantly reduced in T lymphocytes in all treatment groups (telmisartan, CsA, VIVIT, and 4-AP) compared with controls. Antihypertensive function and inhibitory effects of telmisartan on the T lymphocyte NFAT signalling pathway are unlikely to affect the normal immune function of hypertensive patients. Telmisartan may exert anti-inflammatory effects by inhibition of the NFAT signalling pathway in the T lymphocytes of hypertensive patients. © The Author(s) 2016.

  20. [Results of an intervention to reduce potentially inappropriate prescriptions of beta blockers and calcium channel blockers].

    Science.gov (United States)

    Machado-Alba, J E; Giraldo-Giraldo, C; Aguirre Novoa, A

    2016-01-01

    To determine the frequency of simultaneous prescription of β-blockers and calcium channel blockers, notify the cardiovascular risk of these patients to the health care professionals in charge of them, and achieve a reduction in the number of those who use them. Quasi-experimental, prospective study by developing an intervention on medical prescriptions of patients older than 65 years treated between January 1 and July 30, 2014, affiliated to the Health System in 101 cities in Colombia. A total of 43,180 patients received a β-blocker each month, and 14,560 receiving a calcium channel blocker were identified. Educational interventions were performed and an evaluation was made, using sociodemographic and pharmacological variables, on the number of patients that stopped taking any of the two drugs in the following three months. A total of 535 patients, with a mean age 75.8±6.7 years received concomitant β-blockers plus calcium channel blockers. Modification of therapy was achieved in 235 patients (43.9% of users) after 66 educational interventions. In 209 cases (88.9%) one of the two drugs was suspended, and 11.1% changed to other antihypertensive drugs. The variable of being more than 85 years old (OR: 1.93; 95% CI: 1.07-3.50), and receiving concomitant medication with inhibitors of the renin-angiotensin system (OR: 2.16; 95% CI: 1.28-3.65) were associated with increased risk of their doctor changing or stopping the prescription. An improved adherence to recommendations for appropriate use of β-blockers and calcium channel blockers by health service providers was achieved. Intervention programs that reduce potentially inappropriate prescriptions for patients treated for cardiovascular disease should be used more frequently. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  1. Stimulatory Action of Telmisartan, an Antagonist of Angiotensin II Receptor, on Voltage-Gated Na⁺ Current: Experimental and Theoretical Studies.

    Science.gov (United States)

    Chang, Tzu-Tung; Yang, Chia-Jung; Lee, Yu-Chi; Wu, Sheng-Nan

    2018-02-28

    Telmisartan (Tel) is recognized as a non-peptide blocker of AT1R. Whether this agent has any direct effects on ion currents remains unexplored. In whole-cell current recordings, addition of Tel increased the peak amplitude of voltage-gated Na⁺ (NaV) current (INa) accompanied by the increased time constant of INa inactivation in differentiated NSC-34 motor neuron-like cells. Tel-stimulated INa in these cells is unlinked to either blockade of AT1R or activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). In order to explore how this compound affects the amplitude and kinetics of INa in neurons, a Hodgkin-Huxley-based (HH-based) model designed to mimic effect of Tel on the functional activities of neurons was computationally created in this study. In this framework, the parameter for h inactivation gating variable, which was changed in a stepwise fashion, was implemented to predict changes in membrane potentials (V) as a function of maximal Na⁺ (GNa), K⁺ conductance (GK), or both. As inactivation time course of INa was increased, the bifurcation point of V versus GNa became lower, and the range between subcritical and supercritical values at the bifurcation of V versus GK correspondingly became larger. During a slowing in INa inactivation, the critical boundary between GNa and GK was shifted towards the left. Simulation studies demonstrated that progressive slowing in the inactivation time course of INa resulted in unanticipated increase of neuronal excitability by mimicking the effect of Tel in neuronal cells. Collectively, Tel can directly interact with the NaV channel to increase peak INa as well as to slow INa inactivation. It is thus highly likely that the effects of Tel or its structurally similar drugs could be another intriguing mechanism underlying their pharmacological actions in neurons or neuroendocrine cells occurring in vivo.

  2. Effect of telmisartan in combined with L-carnitine on peritoneal dialysis patients

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    Effect of telmisartan in combined with L-carnitine on peritoneal dialysis patients

    2016-07-01

    Full Text Available Objective: To observe the therapeutic effect of telmisartan in combined with L-carnitine on the peritoneal dialysis (PD patients in order to guide the clinical medication. Methods: A total of 80 patients with chronic renal failure (CRF who were admitted in our hospital from November, 2011 to January, 2014 for PD were included in the study and randomized into the treatment group and the control group. The patients in the two groups were routinely performed with PD. The patients in the treatment group were given L-carnitine oral liquid, 10mL/time, 3 times/d, and telmisartan, 80 mg/time, 1 time/d. The patients in the control group were given L-carnitine oral liquid, 10mL/time, 3 times a day. The patients in the two groups were treated for 24 weeks continuously. The serum SCr and BUN levels before and after treatment in the two groups were observed. RRF was calculated. The changes of daily average urine volume and blood pressure before and after treatment in the two groups were observed. Results: After treatment, the reduced degree of SCr and BUN in the treatment group was significantly greater than that in the control group, while the reduced degree of RRF was significantly less than that in the control group (P<0.05. After treatment, the daily urine volume was reduced, but the reduced degree in the treatment group was significantly less than that in the control group (P<0.05. After treatment, SBP and DBP were reduced, but the reduced degree in the treatment group was significantly superior to that in the control group (P<0.05. Conclusions: Telmisartan in combined with L-carnitine applied in PD patients can effectively delay the loss of RRF and the reduction of urine volume, and regulate the blood pressure in order to alleviate the clinical symptoms and improve the patients’ living qualities.

  3. Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue.

    Science.gov (United States)

    Li, Hao; Li, Min; Liu, Ping; Wang, YaPing; Zhang, Heng; Li, HongBin; Yang, ShiFeng; Song, Yan; Yin, YanRong; Gao, Lan; Cheng, Si; Cai, Jun; Tian, Gang

    2016-08-01

    Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level in the high-fat diet-induced MetS rat. In MetS rats, PRAT-derived leptin expression increased concomitant with dysfunction of adipogenesis, and the activities of the angiotensin II-angiotensin II type 1 receptor and the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas receptor axes were imbalanced in PRAT. PRAT-derived leptin from MetS rats promoted proliferation of rat glomerular endothelial cells (GERs) by activating the p38 MAPK (mitogen-activated protein kinase) pathway, thereby contributing to the development of nephropathy. Long-term telmisartan treatment improved metabolic parameters and renal function, decreased the amount of PRAT, promoted adipogenesis, increased the expression of angiotensin-converting enzyme 2, restored balanced activities of the angiotensin II-AT1R and angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axes, and exerted an indirect renoprotective effect on MetS rats by decreasing PRAT-derived leptin release. Our results demonstrate a novel link between nephropathy and PRAT in MetS and show that telmisartan confers an underlying protective effect on visceral adipose tissue and the kidney, suggesting that it has potential as a therapeutic agent for the treatment of MetS-associated nephropathy. © 2016 American Heart Association, Inc.

  4. Rapid determination of telmisartan in human plasma by HPLC using a monolithic column with fluorescence detection and its application to a bioequivalence study.

    Science.gov (United States)

    Zhang, He; Jiang, Yunyun; Wen, Jun; Zhou, Tingting; Fan, Guorong; Wu, Yutian

    2009-11-01

    A rapid HPLC method using a monolithic column with fluorescence detection has been developed for determination of telmisartan in human plasma. Sample preparation was done by protein precipitation with acetonitrile and naproxen was used as IS. The compounds were detected by fluorescence detection, using an excitation wavelength of 300 nm and emission wavelength of 385 nm. Calibration curves of telmisartan were linear in the range of 1-200 ng/mL. The assay was high throughput, sensitive and precise, and it was successfully applied to a bioequivalence study of two formulations of telmisartan.

  5. The non-biphenyl-tetrazole AT1 receptor blocker eprosartan is a unique and robust inverse agonist of the active state of AT1 receptor.

    Science.gov (United States)

    Takezako, Takanobu; Unal, Hamiyet; Karnik, Sadashiva S; Node, Koichi

    2018-03-23

    Diseases such as hypertension and renal-allograft rejection are accompanied by chronic agonist-independent signaling by the angiotensin II (Ang II) type 1 receptor (AT1R). The current treatment paradigm for these diseases embraces the preferred use of inverse agonist AT1R blockers (ARBs). However, variability in the inverse agonist activities of common biphenyl-tetrazole ARBs for the active state of AT1R often leads to treatment failure. Therefore, characterization of robust inverse agonist ARBs for the active state of AT1R is necessary. To identify the robust inverse agonist for active state of AT1R and its molecular mechanism, we performed site-directed mutagenesis, competition binding assay, inositol phosphate production assay and molecular modeling for both ground state wild-type AT1R (WT-AT1R) and active state N111G-AT1R. Although candesartan and telmisartan exhibited weaker inverse agonist activity for N111G-AT1 compared to WT-AT1, only eprosartan exhibited robust inverse agonist activity for both N111G-AT1 and WT-AT1. Specific ligand-receptor contacts for candesartan and telmisartan are altered in the active state N111G-AT1R compare to in the ground state WT-AT1R, suggesting a potential basis for their attenuated inverse agonist activity for the active state of AT1R. In contrast, interactions between eprosartan and N111G-AT1R were not significantly altered, and the inverse agonist activity of eprosartan was robust. These findings suggest that eprosartan may be a better therapeutic option than other ARBs, and that comparative studies investigating eprosartan and other ARBs for the treatment of diseases caused by chronic agonist-independent AT1R activation are warranted. This article is protected by copyright. All rights reserved.

  6. Determining the structural relaxation times deep in the glassy state of the pharmaceutical Telmisartan

    Energy Technology Data Exchange (ETDEWEB)

    Adrjanowicz, K; Paluch, M [Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice (Poland); Ngai, K L [Naval Research Laboratory, Washington, DC 20375-5320 (United States)

    2010-03-31

    By using the dielectric relaxation method proposed recently by Casalini and Roland (2009 Phys. Rev. Lett. 102 035701), we were able to determine the structural alpha-relaxation times deep in the glassy state of the pharmaceutical, Telmisartan. Normally, deep in the glassy state tau{sub a}lpha is so long that it cannot be measured but tau{sub b}eta, which is usually much shorter, can be directly determined. The method basically takes advantage of the connection between the alpha-relaxation and the secondary beta-relaxation of the Johari-Goldstein kind, including a relation between their relaxation times tau{sub a}lpha and tau{sub b}eta, respectively. Thus, tau{sub a}lpha of Telmisartan were determined by monitoring the change of the dielectric beta-loss, epsilon'', with physical aging time at temperatures well below the vitrification temperature. The values of tau{sub a}lpha were compared with those expected by the coupling model (CM). Unequivocal comparison cannot be made in the case of Telmisartan because its beta-loss peak is extremely broad, and the CM predicts only an order of magnitude agreement between the primitive relaxation frequency and the beta-peak frequency. We also made an attempt to analyze all isothermal and aging susceptibility data after transformation into the electric modulus representation. The tau{sub a}lpha found in the glass state by using the method of Casalini and Roland in the modulus representation are similar to those obtained in the susceptibility representation. However, it is remarkable that the stretching parameter beta{sub KWWM} = 0.51 in the electric modulus representation gives more precise fits to the aging data than in the susceptibility representation with beta{sub KWW} = 0.61. Our results suggest that the electric modulus representation may be useful as an alternative to analyze aging data, especially in the case of highly polar glassformers having a large ratio of low frequency and high frequency dielectric

  7. Detection, isolation and characterization of principle synthetic route indicative impurity in telmisartan

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    V. Srinivasan

    2016-11-01

    Full Text Available An unknown impurity was detected in the telmisartan bulk drug (active pharmaceutical ingredient – API using an isocratic reversed-phase high performance liquid chromatography (HPLC. This impurity was isolated by preparative HPLC. Spectral data of the isolated impurity were collected. Based on the spectral data deriving from two dimensional nuclear magnetic spectroscopy (2D-NMR and mass spectrometry (MS, the impurity was characterized as “methyl 4′,4′-dibromo methyl biphenyl-2-carboxylate”. The arrived structure was further confirmed by theoretical studies.

  8. Discovery and Development of Calcium Channel Blockers

    OpenAIRE

    Godfraind, Théophile

    2017-01-01

    In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovere...

  9. Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways

    DEFF Research Database (Denmark)

    He, Hongbo; Yang, Dachun; Ma, Liqun

    2010-01-01

    -gamma expression, whereas neither candesartan nor losartan affected PPAR-delta expression. In vivo, long-term administration of telmisartan significantly reduced visceral fat and prevented high-fat diet-induced obesity in wild-type mice and hypertensive rats but not in PPAR-delta knockout mice. Administration...

  10. Histamine 2 blocker potentiates the effects of histamine 1 blocker in suppressing histamine-induced wheal

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    Dhanya N

    2008-01-01

    Full Text Available Background : Histamine is responsible for the wheal and flare reaction in various allergic conditions. Classical antihistamines are the drugs which block the H 1 receptors and are widely used in various allergic conditions, whereas H 2 blockers are mainly used for acid peptic disease. Although H 1 receptor-mediated actions of histamine are primarily responsible for vasodilatation, vasopermeability, and itching, it has been observed that combined blocking of both H 1 and H 2 receptors may provide better relief. Aim: To compare the efficacy of levocetirizine (H 1 blocker versus levocetirizine and ranitidine (H 2 blocker in suppressing histamine-induced wheal. Methods: Fifteen volunteers were given a single dose of levocetirizine 5 mg on day 1 and a single dose of levocetirizine 5 mg with ranitidine 150 mg twice a day on day 7. A pretest was performed by intradermal histamine prick test. After administration of the drugs, the prick test was repeated at 1 hour, 2, 3, 6, and 24 hours, and the size of the wheal measured and statistically analyzed. Results: At 1 hour, there was no statistically significant difference in the wheal size between levocetirizine alone and the combination of levocetirizine and ranitidine. Levocetirizine with ranitidine resulted in statistically significant reduction of wheal size at 2, 3, 6, and 24 hours when compared with levocetirizine alone. Conclusion: H2 blocker potentiates the effects of an H1 blocker in suppressing histamine-induced wheal.

  11. Prevalence of diabetic nephropathy in Type 2 Diabetes Mellitus in rural communities of Guanajuato, Mexico. Effect after 6 months of Telmisartan treatment

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    Priscyla Zenteno-Castillo

    2015-12-01

    Conclusions: A higher prevalence of DN than that reported in the Mexican National Health Survey (ENSANUT was found. Further research is required in a larger population sample in order to confirm the results of Telmisartan treatment.

  12. [Blood pressure lowering efficacy of telmisartan and amlodipine taking on the morning or at bedtime: ABPM results].

    Science.gov (United States)

    Peng, Gui-cheng; Wang, Yi-fang; Xiao, Yong; Chen, Jian-fu; Yang, Yu; Ye, Yu-liang; Sai, Shuang-qiao; Huang, Jin-xiang

    2013-06-01

    To observe the blood lowering effect of telmisartan and amlodipine taking on the morning or at bedtime in hypertensive patients. A total of 108 individuals with hypertension (grade 2 or above) were randomized to receive telmisartan and amlodipine in one of the following four therapeutic schemes: Group A (26 cases): both medications taken on the morning; Group B (28 cases): both medication taken at bedtime; Group C (27 cases): telmisartan on the morning and amlodipine at bedtime; or Group D (27 cases): amlodipine on the morning and telmisartan at bedtime. ABPM was performed before and after 8 weeks treatment. BP was significantly reduced in 4 groups and the value of 24 hours SBP/DBP decline for each group after treatment was 29.94/16.32, 31.37/18.35, 29.49/17.30 and 25.80/15.51 mm Hg (1 mm Hg = 0.133 kPa) respectively (P 0.05). The night-time BP decline and the distributive difference of dipper, non-dipper, extreme dipper and reverse dipper pattern were similar among groups at both baseline and after various treatment regimens (all P > 0.05) . Morning blood pressure surge (MBPS) after treatment in group B declined more significantly than other groups (P < 0.05). Telmisartan/amlodipine administered either on the morning or at bedtime can effectively reduce blood pressure. The efficacy of BP lowering is independent of the drug taking time. There is a trend both in better BP lowering and less BP variability when two medications are administered at bedtime.

  13. Enhancement of dissolution of Telmisartan through use of solid dispersion technique surface solid dispersion

    Directory of Open Access Journals (Sweden)

    Bhumika Patel

    2012-01-01

    Full Text Available The present study was aimed to increase the solubility of the poorly water soluble drug Telmisartan by using Surface solid dispersion (SSD made of polymers like Poloxamer 407, PEG 6000 by Solvent evaporation method. The drug was solubilized by surfactants and/or polymers then adsorbed onto the surface of extremely fine carriers to increase its surface area and to form the SSD which give the more Surface area for absorption of the drug. A 2 2 full factorial design was used to investigate for each carrier the joint influence of formulation variables: Amount of carrier and adsorbent. Saturation solubility studies shows the improvement in solubility of drug batch SSD 8 give more solubility improvement than the other batch, in-vitro dissolution of pure drug, physical mixtures and SSDs were carried out in that SSDs were found to be effective in increasing the dissolution rate of Telmisartan in form of SSD when compared to pure drug. Also FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and Surface solid dispersion. Furthermore, both DSC and X-ray diffraction showed a decrease in the melting enthalpy and reduced drug crystallinity consequently in SSDs. However, infrared spectroscopy revealed no drug interactions with the carriers.

  14. Dual repressive effect of angiotensin II-type 1 receptor blocker telmisartan on angiotensin II-induced and estradiol-induced uterine leiomyoma cell proliferation.

    Science.gov (United States)

    Isobe, Aki; Takeda, Takashi; Sakata, Masahiro; Miyake, Asako; Yamamoto, Toshiya; Minekawa, Ryoko; Nishimoto, Fumihito; Oskamoto, Yoko; Walker, Cheryl Lyn; Kimura, Tadashi

    2008-02-01

    Although uterine leiomyomas or fibroids are the most common gynecological benign tumor and greatly affect reproductive health and well-being, the pathophysiology and epidemiology of uterine leiomyomas are poorly understood. Elevated blood pressure has an independent, positive association with risk for clinically detected uterine leiomyoma. Angiotensin II (Ang II) is a key biological peptide in the renin-angiotensin system that regulates blood pressure. In this study, we investigated the potential role of Ang II (1-1000 nM) in the proliferation of rat ELT-3 leiomyoma cells in vitro. RT-PCR and western blot analysis with cell proliferation and DNA transfection assays were performed to determine the mechanism of action of Ang II. Ang II induced ELT-3 leiomyoma cell proliferation (P estradiol-induced cell proliferation (P < 0.01). AT(1)R, but not AT(2)R, plays a role in Ang II-induced ELT-3 cell proliferation. These experimental findings in vitro highlight the potential role of Ang II in the proliferation of leiomyoma cells.

  15. Beta Blockers for the Prevention of Acute Exacerbations of COPD

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0705 TITLE: Beta Blockers for the Prevention of Acute Exacerbations of COPD PRINCIPAL INVESTIGATOR: Mark T...SUBTITLE 5a. CONTRACT NUMBER Beta Blockers for the Prevention of Acute Exacerbations of COPD 5b. GRANT NUMBER W81XWH-15-1-0705 5c. PROGRAM ELEMENT...period the following article was published: β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD

  16. Absent Lung Deflation Because of Blockade Using an Endobronchial Blocker.

    Science.gov (United States)

    Garg, Rakesh; Pandit, Anuja

    2017-06-01

    One-lung ventilation is required for various thoracic procedures. In addition, various strategies such as the use of double-lumen tube, uninvent tubes, and endobronchial blocker have been used for performing one-lung ventilation. Each of these techniques has its advantages and limitations. Certain factors for failure of endobronchial blocker to provide lung deflation has been described in literature. We report a different aetiology of failure of lung deflation, although the endobronchial blocker was appropriately placed.

  17. Influência do bloqueador de receptor de angiotensina (Losartana potássica na função renal e pressão arterial em cães GRMD Influence of angiotensin receptor blocker of renal function and arterial pression in GRMD dogs

    Directory of Open Access Journals (Sweden)

    Marina Brito Silva

    2009-04-01

    Full Text Available A distrofia muscular de Duchenne (DMD é uma alteração neuromuscular caracterizada por contínua necrose muscular e degeneração, com eventual fibrose e infiltração por tecido adiposo. O aumento progressivo da fibrose intersticial no músculo impede a migração das células miogênicas, necessárias para a formação muscular. O modelo canino constitui-se nas melhores fenocópias da doença em humanos, quando comparados com outros modelos animais com distrofia. O tratamento antifibrose de pacientes DMD, tendo como alvo os mediadores da citocina, TGF-beta, e o tratamento com antiinflamatórios, podem limitar a degeneração muscular e contribuir para a melhora do curso da doença. O presente estudo teve como objetivo observar os possíveis efeitos adversos na fisiologia renal, por meio de avaliação bioquímica sanguínea e da pressão arterial, verificando a viabilidade do uso do Losartan (um inibidor de TGF-beta nos cães afetados pela distrofia muscular. Foram utilizados quatro cães adultos, sendo dois machos e duas fêmeas. Utilizou-se a dose de 50mg de Losartan, administrada via oral, uma vez ao dia. Os exames clínicos, bem como alterações na função renal, o nível do potássio sérico e a pressão arterial não evidenciaram reação adversa durante todo o período do experimento. O uso de Losartan, por um período de 9 semanas, mostrou-se como uma terapia segura para o tratamento antifibrótico em cães adultos, não afetando a função renal ou pressão arterial dos animais.Duchenne muscular dystrophy (DMD is a neuromuscular disorder characterized by a continuous muscle necrosis and degeneration with eventual fibrosis and fatty tissue infiltration. Progressive increase in muscle interstitial fibrosis prevents the movement of myogenic cells, which is necessary for myotube formation. Canine model is the best phenocopies of the disease in humans when comparing with others animal models with dystrophy. Anti-fibrotic treatment of DMD patients, targeting the cytokine mediators, TGF-beta, and the treatment with antiinflammatories, may limit muscle degeneration and contribute for the improvement of the course of the illness. This work aimed to verify the possible adverse effects in renal physiology by means of evaluation sanguineous biochemist and arterial pressure, in order to verifying the viability of Losartan (a TGF-beta inhibiter in affected dogs by muscle dystrophy. It was used four adults dogs, two of each gender. A dose of 50mg of Losartan was orally given once a day. The clinical exams, the kidney function, arterial blood pressure and potassium level did not show any adverse effect through the experimental period. Losartan utilization showed to be a safe therapy for the antifibrotic treatment in adults dogs, not affecting neither the kidney function nor the arterial blood pressure.

  18. Detecting Anti Ad-blockers in the Wild

    Directory of Open Access Journals (Sweden)

    Mughees Muhammad Haris

    2017-07-01

    Full Text Available The rise of ad-blockers is viewed as an economic threat by online publishers who primarily rely on online advertising to monetize their services. To address this threat, publishers have started to retaliate by employing anti ad-blockers, which scout for ad-block users and react to them by pushing users to whitelist the website or disable ad-blockers altogether. The clash between ad-blockers and anti ad-blockers has resulted in a new arms race on the Web. In this paper, we present an automated machine learning based approach to identify anti ad-blockers that detect and react to ad-block users. The approach is promising with precision of 94.8% and recall of 93.1%. Our automated approach allows us to conduct a large-scale measurement study of anti ad-blockers on Alexa top-100K websites. We identify 686 websites that make visible changes to their page content in response to ad-block detection. We characterize the spectrum of different strategies used by anti ad-blockers. We find that a majority of publishers use fairly simple first-party anti ad-block scripts. However, we also note the use of third-party anti ad-block services that use more sophisticated tactics to detect and respond to ad-blockers.

  19. Systematic review of use of β-blockers in sepsis

    Directory of Open Access Journals (Sweden)

    Cyril Jacob Chacko

    2015-01-01

    Conclusion: There is insufficient evidence to justify the routine use of β-blockers in sepsis. A large adequately powered multi-centered randomized controlled clinical trial is required to address the question on the efficacy of β-blocker usage in sepsis. This trial should also consider a number of important questions including the choice of β-blocker used, optimal dosing, timing of intervention, duration of intervention and discontinuation of the drug. Until such time based on the available evidence, there is no place for the use of β-blockers in sepsis in current clinical practice.

  20. Calcium channel blockers for primary Raynaud's phenomenon.

    Science.gov (United States)

    Ennis, Holly; Hughes, Michael; Anderson, Marina E; Wilkinson, Jack; Herrick, Ariane L

    2016-02-25

    Calcium channel blockers are the most commonly prescribed drugs for people with primary Raynaud's phenomenon. Primary Raynaud's phenomenon is a common condition characterised by an exaggerated vasospastic response to cold or emotion: classically the digits (fingers and toes) turn white, then blue, then red. This is an update of the review first published in 2014. To assess the effects of different calcium channel blockers for primary Raynaud's phenomenon as determined by attack rates, severity scores, participant-preference scores and physiological measurements. For this update the Cochrane Vascular Trial Search Co-ordinator searched the Specialised Register (last searched January 2016) and the Cochrane Register of Studies (CENTRAL) (2015, Issue 12). In addition the TSC searched clinical trials databases. Randomised controlled trials evaluating the effects of oral calcium channel blockers for the treatment of primary Raynaud's phenomenon. Three review authors independently assessed the trials for inclusion and their quality, and extracted the data. Data extraction included adverse events. We contacted trial authors for missing data. We included seven randomised trials with 296 participants. Four trials examined nifedipine and the remainder nicardipine. Comparisons were with placebo in six trials and with both dazoxiben and placebo in one trial (only the nifedipine versus placebo data were used within this review). Treatment with oral calcium channel blockers was minimally effective in primary Raynaud's phenomenon at decreasing the frequency of attacks (standardised mean difference of 0.23; 95% confidence interval (CI) 0.08 to 0.38, P = 0.003). This translates to 1.72 (95% CI 0.60 to 2.84) fewer attacks per week on calcium channel blockers compared to placebo. One trial provided details on duration of attacks reporting no statistically significant difference between the nicardipine and placebo groups (no P value reported). Only two trials provided any detail of

  1. In a subgroup of high-risk Asians, telmisartan was non-inferior to ramipril and better tolerated in the prevention of cardiovascular events.

    Directory of Open Access Journals (Sweden)

    Antonio L Dans

    2010-12-01

    Full Text Available Results of the recently published ONTARGET study (The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial showed that telmisartan (80 mg/day was non-inferior to ramipril (10 mg/day in reducing cardiovascular events. Clinicians in Asia doubt tolerability of these doses for their patients. We therefore analyzed data from this study and a parallel study TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease. Our objectives were to compare Asians and non-Asians with respect to the following: 1 Effectiveness of telmisartan vs. ramipril in reducing cardiovascular events;2 Proportions who reached the full dose of telmisartan, ramipril or placebo; and3 Proportions of overall discontinuations, and discontinuations due to adverse effects.The ONTARGET study randomized 25,620 patients at risk of cardiovascular events to ramipril, telmisartan, or their combination. The primary composite endpoint was death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. TRANSCEND randomized 5926 high-risk patients with a history of intolerance to ACE-inhibitors to telmisartan or placebo. The primary outcome was the same. In this substudy, we compared Asians and non-Asians as to how well they tolerated telmisartan (given in both studies and ramipril (given in ONTARGET.1 Telmisartan was non-inferior to ramipril in lowering the primary endpoint among Asians (RR = 0.92; 95% CI: 0.74, 1.13; 2 more Asians achieved the full dose of either drug; 3 less withdrew (overall; and 4 less withdrew for adverse effects. Furthermore, telmisartan was better tolerated than ramipril. This advantage was greater among Asians.Although Asians had lower BMI than non-Asians, Asians tolerated both drugs better. Regulatory agencies require reporting of safety and effectiveness data by ethnicity, but few comply with this requirement. This study shows that safety data

  2. Comparative study of telmisartan tablets prepared via the wet granulation method and pritor™ prepared using the spray-drying method.

    Science.gov (United States)

    Park, Junsung; Park, Hee Jun; Cho, Wonkyung; Cha, Kwang-Ho; Yeon, Wonki; Kim, Min-Soo; Kim, Jeong-Soo; Hwang, Sung-Joo

    2011-03-01

    The wet granulation method was successfully used to manufacture amorphous telmisartan tablets (CNU) for comparison with the spray-drying method, used for Pritor™. Drug crystallinity in the tablet was characterized using differential scanning calorimetry and powder X-ray diffraction, and pharmaceutical properties of the tablets such as hardness, friability, water absorption, and in vitro dissolution in pH 1.2, 4.0, 6.8 and 7.5 were characterized. Especially with regard to the water absorption feature, the CNU tablets showed better performance by maintaining their original structures and by absorbing less water. Since both Pritor™ and CNU tablets had similar physical properties of crystallinity, hardness, friability, and > 50 f(2) value in an in vitro dissolution study, the bioequivalence of CNU tablets should be analyzed in a future in vivo study. Therefore, telmisartan tablets can be produced using a more economical and easier method than that used to produce Pritor™ tablets.

  3. Beta blockers and their combinations in the management of ...

    African Journals Online (AJOL)

    Review Article: Beta blockers and their combinations in the management of hypertension. 409. Vol 54 No 5. S Afr Fam Pract 2012. Introduction. Beta blockers have been prescribed for the treatment of primary hypertension for a very long time. Currently, it is doubtful whether this is still a good idea. In fact, many are of the ...

  4. Beta-blocker use and fall risk in older individuals

    NARCIS (Netherlands)

    Ham, Annelies C.; Dijk, van S.C.; Swart, Karin M.A.; Enneman, Anke W.; Zwaluw, van der Nikita L.; Brouwer-Brolsma, Elske M.; Schoor, van Natasja M.; Zillikens, M.C.; Lips, Paul; Groot, de Lisette C.P.G.M.; Hofman, Albert; Witkamp, Renger F.; Uitterlinden, André G.; Stricker, Bruno H.; Velde, van der Nathalie

    2017-01-01

    Aims: To investigate the association between use of β-blockers and β-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism - and fall risk. Methods: Data from two prospective studies were used, including community-dwelling

  5. Calcium channel blockers in cardiovascular pharmacotherapy.

    Science.gov (United States)

    Godfraind, Theophile

    2014-11-01

    This paper summarizes the pharmacological properties of calcium channel blockers (CCBs), their established therapeutic uses for cardiovascular disorders and the current improvement of their clinical effects through drug combinations. Their identification resulted from study of small molecules including coronary dilators, which were named calcium antagonists. Further experiments showed that they reduced contraction of arteries by inhibiting calcium entry and by interacting with binding sites identified on voltage-dependent calcium channels. This led to the denomination calcium channel blockers. In short-term studies, by decreasing total peripheral resistance, CCBs lower arterial pressure. By unloading the heart and increasing coronary blood flow, CCBs improve myocardial oxygenation. In long-term treatment, the decrease in blood pressure is more pronounced in hypertensive than in normotensive patients. A controversy on the safety of CCBs ended after a large antihypertensive trial (ALLHAT) sponsored by the National Heart, Lung, and Blood Institute. There are two main types of CCBs: dihydopyridine and non-dihydropyridine; the first type is vascular selective. Dihydropyrines are indicated for hypertension, chronic, stable and vasospastic angina. Non-dihydropyridines have the same indications plus antiarrythmic effects in atrial fibrillation or flutter and paroxysmal supraventricular tachycardia. In addition, CCBs reduced newly formed coronary lesions in atherosclerosis. In order to reach recommended blood pressure goals, there is a recent therapeutic move by combination of CCBs with other antihypertensive agents particularly with inhibitors acting at the level of the renin-angiotensin system. They are also combined with statins. Prevention of dementia has been reported in hypertensive patients treated with nitrendipine, opening a way for further studies on CCBs' beneficial effect in cognitive deterioration associated with aging. © The Author(s) 2014.

  6. Effects of telmisartan on the expression of NADPH oxidase subunits in the myocardium of type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Jia-wei LI

    2011-10-01

    Full Text Available Objective To explore the effect of telmisartan on the expression of NADPH oxidase subunits p22phox and NOX4 in the myocardiam of type 2 diabetic rats.Methods Thirty-six male Wistar rats were randomly divided into two groups: normal control group(group A,n=10,diabetic model group(n=26.Type 2 diabetic model was established by high-fat and high-sugar diet followed by intraperitoneal injection of a low dose of streptozotocin(STZ.After the model was reproduced successfully,20 diabetic rats were randomly divided into diabetic subgroup(group B,n=10 and telmisartan-treated subgroup(group C,n=10.Rats in group C were orally administered telmisartan(5mg/kg/d,and rats in group A and B were given equivalent volume of normal saline.All rats were sacrificed 12 weeks after treatment.The mRNA expressions of myocardial p22phox and NOX4 were detected by real-time fluorescence quantitative PCR,and the protein expressions of myocardial connective tissue growth factor(CTGF and copper-zinc-superoxide dismutase(Cu-Zn-SOD were detected by immunohistochemical staining.Results Compared with group A,the ratio of heart/body weight,the mRNA expression of myocardial p22phox and NOX4,and the protein expression of myocardial CTGF increased significantly in group B,and the protein expression of myocardial Cu-Zn-SOD decreased significantly(P 0.05.Conclusions Telmisartan can down-regulate the over-expression of myocardial NOX4 and p22phox mRNA in type 2 diabetic rats,lessen the myocardial damage induced by oxidative stress,thus plays a protective role in the myocardium of diabetic rats.

  7. Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice.

    Directory of Open Access Journals (Sweden)

    Muralikrishna Gangadharan Komala

    Full Text Available BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2 is the main luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria and improved glycaemic control. Drugs inhibiting this transporter have recently been approved for clinical use and have been suggested to have potential renoprotective benefits by limiting glycotoxicity in the proximal tubule. We aimed to determine the renoprotective benefits of empagliflozin, an SGLT2 inhibitor, independent of its glucose lowering effect. RESEARCH DESIGN AND METHODS: We induced diabetes using a low dose streptozotocin protocol in 7-8 week old endothelial nitric oxide (eNOS synthase knockout mice. We measured fasting blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio. Renal histology was assessed for inflammatory and fibrotic changes. Renal cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes were compared to diabetic animals receiving the angiotensin receptor blocker telmisartan (current best practice. RESULTS: Diabetic mice had high matched blood glucose levels. Empagliflozin did not attenuate diabetes-induced albuminuria, unlike telmisartan. Empagliflozin did not improve glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis, while telmisartan attenuated these. Empagliflozin did not modify tubular toll-like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the upregulation of macrophage chemoattractant protein-1 (MCP-1, transforming growth factor β1 and fibronectin mRNA observed in the diabetic animals, while telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression in comparison to untreated diabetic mice. However no significant difference was found in protein expression of GLUT1 or SGLT2 among the

  8. Telmisartan/hydrochlorothiazide versus valsartan/hydrochlorothiazide in obese hypertensive patients with type 2 diabetes: the SMOOTH study

    Directory of Open Access Journals (Sweden)

    Koval Stephen

    2007-10-01

    Full Text Available Abstract Background The Study of Micardis (telmisartan in Overweight/Obese patients with Type 2 diabetes and Hypertension (SMOOTH compared hydrochlorothiazide (HCTZ plus telmisartan or valsartan fixed-dose combination therapies on early morning blood pressure (BP, using ambulatory BP monitoring (ABPM. Methods SMOOTH was a prospective, randomized, open-label, blinded-endpoint, multicentre trial. After a 2- to 4-week, single-blind, placebo run-in period, patients received once-daily telmisartan 80 mg or valsartan 160 mg for 4 weeks, with add-on HCTZ 12.5 mg for 6 weeks (T/HCTZ or V/HCTZ, respectively. At baseline and week 10, ambulatory blood pressure (ABP was measured every 20 min and hourly means were calculated. The primary endpoint was change from baseline in mean ambulatory systolic and diastolic blood pressure (SBP; DBP during the last 6 hours of the 24-hour dosing interval. Results In total, 840 patients were randomized. At week 10, T/HCTZ provided significantly greater reductions versus V/HCTZ in the last 6 hours mean ABP (differences in favour of T/HCTZ: SBP 3.9 mm Hg, p Conclusion In high-risk, overweight/obese patients with hypertension and type 2 diabetes, T/HCTZ provides significantly greater BP lowering versus V/HCTZ throughout the 24-hour dosing interval, particularly during the hazardous early morning hours.

  9. Retracted: Physiologically based pharmacokinetic predictions of intestinal BCRP-mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans.

    Science.gov (United States)

    Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Gab-Jin; Lee, Jongtae; Hong, Taegon; Jeon, Sangil; Yim, Dong-Seok

    2017-07-01

    'Physiologically based pharmacokinetic predictions of intestinal BCRP-mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans' by Soo Hyeon Bae, Wan-Su Park, Seunghoon Han, Gab-jin Park, Jongtae Lee, Taegon Hong, Sangil Jeon and Dong-Seok Yim The above article, published online on 06 February 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, K. Sandy Pang, and John Wiley & Sons, Ltd. The authors retracted the paper due to errors associated with use of log D vs. log P of telmisartan as inputs of the PBPK model. The authors concluded that there are too many changes in the article to be resolved by an Erratum, and had requested a retraction. Reference Bae, S. H., Park, W.-S., Han, S., Park, G., Lee, J., Hong, T., Jeon, S., and Yim, D.-S. (2016) Physiologically based pharmacokinetic predictions of intestinal BCRP-mediated effect of telmisartan on the pharmacokinetics of rosuvastatin in humans. Biopharm. Drug Dispos., doi: 10.1002/bdd.2060. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Influence of additional risk factors on the antihypertensive efficacy of eprosartan and telmisartan in patients with essential hypertension

    Directory of Open Access Journals (Sweden)

    V. V. Syvolap

    2017-12-01

    Full Text Available Objective. The aim of this study is to determine the effect of additional risk factors on blood pressure parameters, cardiovascular remodeling and the state of vegetative balance of the heart rhythm in patients with stage II essential hypertension (EH under treatment with eprosartan and telmisartan. Materials and methods. The study included 100 patients with stage II essential hypertension (EH, 1–2 degrees with a low and moderate risk of developing cardiovascular complications. The smoker's status was 30.0 %, hypercholesterolemia more than 5 mmol/l – 69.0 %, overweight and obesity – 82.0 % of patients with EH. By randomisation, half of the patients received eprosartan in a daily dose of 600 mg, the rest received telmisartan at a daily dose of 80 mg for 6 months. Before the start of treatment and after 6 months of therapy, all the patients were subjected to the evaluation of general physical examinations, calculation of body mass index, determination of serum TC level, ECG Holter monitoring with analysis of heart rate variability, ambulatory blood pressure monitoring, echocardiography and duplex pulsed wave dopplerography of extracranial and intracranial vessels. Two weeks before the study, the patients did not take any antihypertensive drugs. Results. In patients with EH with additional risk factors using of eprosartan for 6 months is accompanied by a significant decrease in "office" SBP by 30.0 %, DBP by 21.6 %, PBP by 41.4 % and avg. BP by 25.5 %, regression of myocardial hypertrophy and improvement of diastolic function of the left ventricle. Eprosartan demonstrated a high antihypertensive efficacy on the effect on SBP in patients with EH with the presence/absence of tobacco smoking. However, the effect of eprosartan on DBP was better in patients with EH who do not have the status of a smoker. All the patients with EH, regardless of the presence or absence of an elevated level of total cholesterol, reached the target level of SBP under

  11. ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in patients with mild-to-moderate essential hypertension.

    Science.gov (United States)

    Amerena, J; Pappas, S; Ouellet, J P; Williams, L; O'Shaughnessy, D

    2002-01-01

    In this multicentre, prospective, randomized, open-label, blinded-endpoint (PROBE) study, the efficacy of 12 weeks' treatment with once-daily telmisartan 40-80 mg and enalapril 10-20 mg was evaluated using ambulatory blood pressure monitoring (ABPM) in 522 patients with mild-to-moderate essential hypertension. Patients were titrated to the higher dose of study drug at week 6 if mean seated diastolic blood pressure (DBP) was > or = 90 mmHg. The primary endpoint was the change from baseline in ambulatory DBP in the last 6 h of the 24-h dosing interval after 12 weeks' treatment. Telmisartan and enalapril produced similar reductions from baseline in DBP and systolic blood pressure (SBP) over all ABPM periods evaluated (last 6 h, 24-h, daytime and night-time). Telmisartan produced a significantly greater reduction in mean seated trough DBP, measured unblinded with an automated ABPM device in the clinic, amounting to a difference of -2.02 mmHg (P ABPM device. Both treatments were well tolerated. Compared with telmisartan, enalapril was associated with a higher incidence of cough (8.9% versus 0.8%) and hypotension (3.9% versus 1.1%). Therefore, telmisartan may provide better long-term compliance and, consequently, better blood pressure control than enalapril.

  12. Involvement of Proteasome and Macrophages M2 in the Protection Afforded by Telmisartan against the Acute Myocardial Infarction in Zucker Diabetic Fatty Rats with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    C. Di Filippo

    2014-01-01

    Full Text Available This study investigated the involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty (ZDF rats with metabolic syndrome. ZDF rats were treated for three weeks with telmisartan at doses of 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25 min occlusion of the left descending coronary artery followed by 2 h reperfusion (I/R. At the end of the I/R period, biochemical, immunohistochemical, and echocardiographic evaluations were done. Telmisartan treatment (7 mg/kg and 12 mg/kg reduced the myocardial infarct size, the expression of proteasome subunits 20S and 26S, and the protein ubiquitin within the heart. The compound has led to an increased M2 macrophage phenotype within the cardiac specimens and a modification of the cardiac cytokine and chemokine profile. This was functionally translated in improved cardiac performance as evidenced by echography after 2 h reperfusion. 7 mg/kg/day telmisartan was sufficient to improve the left ventricular ejection fraction LVEF of the rat heart recorded after I/R (e.g., vehicle 38 ± 2.2%; telmisartan 54 ± 2.7% and was sufficient to improve the diastolic function and the myocardial performance index up to values of 0.6 ± 0.01 measured after I/R.

  13. The pharmacokinetic-pharmacodynamic model of telmisartan and hydrochlorothiazide on blood pressure and plasma potassium after long-term administration in spontaneously hypertensive rats.

    Science.gov (United States)

    Yu, Dan; Chen, Yuancheng; Hao, Kun

    2015-12-01

    A pharmacokinetic-pharmacodynamic model was developed to describe the time course of blood pressure and plasma potassium after long-term telmisartan and/or hydrochlorothiazide administration in spontaneously hypertensive rats. The spontaneously hypertensive rats were administered once daily for 6 weeks. The drug concentration, blood pressure and plasma potassium were monitored for several points. The time courses of blood pressure and plasma potassium were described by indirect response pharmacokinetic-pharmacodynamic model. The synergistic antihypertensive pharmacodynamic interaction between telmisartan and hydrochlorothiazide was observed, which was simulated by the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after co-administration of the two drugs. For plasma potassium, when hydrochlorothiazide administrated alone, the plasma potassium reached to a low steady-state level at 4.64 mmol/L for 6 weeks. The plasma potassium increased to a steady-state level at 4.84 mmol/L after co-administration of telmisartan. The time courses of plasma potassium were successfully characterized by indirect response pharmacokinetic-pharmacodynamic model after long-term administration of telmisartan and/or hydrochlorothiazide. The model captured turnovers of blood pressure and plasma potassium in the different time phases and dose conditions. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  14. Discovery and Development of Calcium Channel Blockers

    Science.gov (United States)

    Godfraind, Théophile

    2017-01-01

    In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan) and Heibrunn (USA) experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB) of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are important factors of

  15. Discovery and Development of Calcium Channel Blockers.

    Science.gov (United States)

    Godfraind, Théophile

    2017-01-01

    In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan) and Heibrunn (USA) experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB) of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are important factors of

  16. Discovery and Development of Calcium Channel Blockers

    Directory of Open Access Journals (Sweden)

    Théophile Godfraind

    2017-05-01

    Full Text Available In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan and Heibrunn (USA experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are

  17. Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction A Network Meta-Analysis

    NARCIS (Netherlands)

    Burnett, Heather; Earley, Amy; Voors, Adriaan A.; Senni, Michele; McMurray, John. J. V.; Deschaseaux, Celine; Cope, Shannon

    Background-Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin

  18. Effect of aliskiren, telmisartan and torsemide on cardiac dysfunction in l-nitro arginine methyl ester (l-NAME induced hypertension in rats

    Directory of Open Access Journals (Sweden)

    Sawsan A. Sadek

    2015-11-01

    Full Text Available Comparative study of cardio protective effect of aliskiren, telmisartan, and torsemide was carried out on l-nitro arginine methyl ester (l-NAME induced hypertension in rats. The three drugs were given daily for 8 weeks simultaneously with l-NAME, with a control group for each drug and l-NAME. The degree of protection was assessed by measurement of systolic blood pressure and heart rate of animals every two weeks. At the end of the experimental period blood sampling was carried out for estimation of the level of NO2−/NO3−. After which animals were sacrificed for heart dissection to detect collagen types I and III gene expression. Histopathological study was done to evaluate the extension of collagen deposits. The study revealed that the three drugs decreased blood pressure significantly compared to l-NAME. There was no significant difference between aliskiren and telmisartan in all measurements, but there was significant decrease in measurements of both aliskiren and telmisartan treated groups compared to torsemide starting from 4th week. There were insignificant changes in pulse rate values between the three l-NAME treated groups through the experiment. The three drugs significantly increased NO compared to l-NAME. Collagen I and III gene expression was significantly decreased by the three drugs but the highest percentage of inhibition was with telmisartan compared to l-NAME. Comparing the percentage inhibition of cardiac fibrosis, there was insignificant difference between telmisartan and torsemide treated groups while both were superior to aliskiren. In conclusion, further experimental studies are required to elucidate the potential cardioprotective mechanisms of aliskiren, telmisartan and torsemide, and assess their efficacy in treatment of heart failure.

  19. Telmisartan in the diabetic murine model of acute myocardial infarction: dual contrast manganese-enhanced and delayed enhancement MRI evaluation of the peri-infarct region.

    Science.gov (United States)

    Toma, Ildiko; Kim, Paul J; Dash, Rajesh; McConnell, Michael V; Nishimura, Dwight; Harnish, Phillip; Yang, Phillip C

    2016-02-05

    A novel MRI technique, employing dual contrast manganese-enhanced MRI (MEMRI) and delayed enhancement MRI (DEMRI), can evaluate the physiologically unstable peri-infarct region. Dual contrast MEMRI-DEMRI enables comprehensive evaluation of telmisartan to salvage the peri-infarct injury to elucidate the underlying mechanism of restoring the ischemic cardiomyopathy in the diabetic mouse model. Dual contrast MEMRI-DEMRI was performed on weeks 1, 2, and 4 following initiation of telmisartan treatment in 24 left anterior descendent artery ligated diabetic mice. The MRI images were analyzed for core infarct, peri-infarct, left ventricular end-diastolic, end-systolic volumes, and the left ventricular ejection fraction (LVEF). Transmission electron microscopy (TEM) and real-time PCR were used for ex vivo analysis of the myocardium. Telmisartan vs. control groups demonstrated significantly improved LVEF at weeks 1, 2, and 4, respectively (33 ± 7 %*** vs. 19 ± 5 %, 29 ± 3 %*** vs. 22 ± 4 %, and 31 ± 2 %*** vs 18 ± 6 %, ***p infarct injury. Telmisartan group significantly salvaged the peri-infarct injury. The myocardial effects were validated by TEM, which confirmed the presence of the injured but viable cardiomyocyte morphology in the peri-infarct region and by flow cytometry of venous blood, which demonstrated significantly increased circulating endothelial progenitor cells (EPCs). The improved cardiac function in ischemic cardiomyopathy of diabetic mice by telmisartan is attributed to the attenuation of the peri-infarct injury by the angiogenic effects of EPCs to salvage the injured cardiomyocytes. Dual-contrast MEMRI-DEMRI technique tracked the therapeutic effects of telmisartan on the injured myocardium longitudinally.

  20. Beta Blockers for the Prevention of Acute Exacerbations of COPD

    Science.gov (United States)

    2016-10-01

    conference papers, and presentations. Nothing to report. Website(s) or other Internet site(s) The trial has been listed on ClinicalTrials.gov...known to be triggered by β-blockers or β-blocker withdrawal including myasthenia gravis, periodic hypokalemic paralysis , pheochromocytoma and...on the observations in the control groups of the prior COPD Clinical Research Network trials of azithromycin and simvastatin of similar design.17 18

  1. β-Blocker treatment during pregnancy and adverse pregnancy outcomes

    DEFF Research Database (Denmark)

    Petersen, Kasper Meidahl; Jimenez-Solem, Espen; Andersen, Jon Traerup

    2012-01-01

    To investigate the association between exposure to β-blockers during pregnancy and the risk of being born small for gestational age (SGA), preterm birth and perinatal mortality in a nationwide cohort.......To investigate the association between exposure to β-blockers during pregnancy and the risk of being born small for gestational age (SGA), preterm birth and perinatal mortality in a nationwide cohort....

  2. [Focus on beta-blockers for vascular specialists in 2012].

    Science.gov (United States)

    Mairesse, S; Blacher, J; Safar, M-E

    2011-12-01

    Since they were launched on the market in 1964, cardiovascular indications for beta-blockers have been validated and accepted worldwide. Numerous studies and meta-analysis have confirmed their benefits. They reduce mortality in post infarction and acute coronary syndrome populations and also in people with stable coronary heart disease. Moreover, heart failure with systolic left ventricular dysfunction is a major indication for this therapeutic class, providing a 30% decrease in mortality. In patients with permanent atrial fibrillation, beta-blockers are recommended for rate control. In hypertension patients, first-line drug treatment with beta-blockers is currently discussed. Indeed, several studies have shown that patients randomized in the beta-blocker arms experienced more coronary heart and cerebrovascular diseases than comparators. Their lesser effect on central blood pressure decrease could partially explain those results. Nevertheless, beta-blockers are still considered as first-line drugs for hypertension in the French and European guidelines. Long-term comparative studies focusing on central blood pressure are needed. Concerning the other indications for beta-blockers in vascular diseases, their use perioperatively to reduce surgical cardiovascular risk raised much hope, but the most recent results are disappointed and even suggest possible higher mortality. Finally, except for patients with critical ischemia of the lower limbs, presence of peripheral artery disease should probably be considered as a condition favoring their prescription. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  3. Preparation and Characterization of Liquisolid Compacts for Improved Dissolution of Telmisartan

    Directory of Open Access Journals (Sweden)

    Naveen Chella

    2014-01-01

    Full Text Available The objective of the present work was to obtain pH independent and improved dissolution profile for a poorly soluble drug, telmisartan using liquisolid compacts. Liquisolid compacts were prepared using Transcutol HP as vehicle, Avicel PH102 as carrier, and Aerosil 200 as a coating material. The formulations were evaluated for drug excipient interactions, change in crystallinity of drug, flow properties, and general quality control tests of tablets using Fourier transform infrared (FTIR spectroscopy, differential scanning calorimetry (DSC, X-ray diffraction (XRD, angle of repose, and various pharmacopoeial tests. In vitro dissolution studies were performed at three pH conditions (1.2, 4.5 and 7.4. Stability studies were performed at 40°C and 75% RH for three months. The formulation was found to comply with Indian pharmacopoeial limits for tablets. FTIR studies confirmed no interaction between drug and excipients. XRD and DSC studies indicate change/reduction in crystallinity of drug. Dissolution media were selected based on the solubility studies. The optimized formulation showed pH independent release profile with significant improvement P<0.005 in dissolution compared to plain drug and conventional marketed formulation. No significant difference was seen in the tablet properties, and drug release profile after storage for 3 months.

  4. Development of dissolution test method for a telmisartan/amlodipine besylate combination using synchronous derivative spectrofluorimetry

    Directory of Open Access Journals (Sweden)

    Panikumar Durga Anumolu

    2014-04-01

    Full Text Available The dissolution process is considered an important in vitro tool to evaluate product quality and drug release behavior. Single dissolution methods for the analysis of combined dosage forms are preferred to simplify quality control testing. The objective of the present work was to develop and validate a single dissolution test for a telmisartan (TEL and amlodipine besylate (AML combined tablet dosage form. The sink conditions, stability and specificity of both drugs in different dissolution media were tested to choose a discriminatory dissolution method, which uses an USP type-II apparatus with a paddle rotating at 75 rpm, with 900 mL of simulated gastric fluid (SGF without enzymes as the dissolution medium. This dissolution methodology provided good dissolution profiles for both TEL and AML and was able to discriminate changes in the composition and manufacturing process. To quantify both drugs simultaneously, a synchronous first derivative spectrofluorimetric method was developed and validated. Drug release was analyzed by a fluorimetric method at 458 nm and 675 nm for AML and TEL, respectively. The dissolution method was validated as per ICH guidance.

  5. Photochemical fate of beta-blockers in NOM enriched waters

    International Nuclear Information System (INIS)

    Wang, Ling; Xu, Haomin; Cooper, William J.; Song, Weihua

    2012-01-01

    Beta-blockers, prescribed for the treatment of high blood pressure and for long-term use after a heart attack, have been detected in surface and ground waters. This study examines the photochemical fate of three beta-blockers, atenolol, metoprolol, and nadolol. Hydrolysis accounted for minor losses of these beta-blockers in the pH range 4–10. The rate of direct photolysis at pH 7 in a solar simulator varied from 6.1 to 8.9 h −1 at pH 7. However, the addition of a natural organic matter (NOM) isolate enhanced the photochemical loss of all three compounds. Indirect photochemical fate, generally described by reactions with hydroxyl radical (·OH) and singlet oxygen ( 1 ΔO 2 ), and, the direct reaction with the triplet excited state, 3 NOM ⁎ , also varied but collectively appeared to be the major loss factor. Bimolecular reaction rate constants of the three beta-blockers with 1 ΔO 2 and ·OH were measured and accounted for 0.02–0.04% and 7.2–38.9% of their loss, respectively. These data suggest that the 3 NOM ⁎ contributed 50.6–85.4%. Experiments with various 3 NOM ⁎ quenchers supported the hypothesis that it was singly the most important reaction. Atenolol was chosen for more detailed investigation, with the photoproducts identified by LC–MS analysis. The results suggested that electron-transfer could be an important mechanism in photochemical fate of beta-blockers in the presence of NOM. - Highlights: ► Photochemical degradation of beta-blockers in the simulated natural waters. ► Reactive Oxygen Species play a minor role in the indirect photodegradation. ► The loss of beta-blockers results from direct reaction with 3 DOM ⁎ .

  6. A multicenter, open-label study of the efficacy and safety of telmisartan in mild to moderate hypertensive patients

    Directory of Open Access Journals (Sweden)

    Plavnik Frida Liane

    2002-01-01

    Full Text Available OBJECTIVE: To evaluate the efficacy and tolerability of telmisartan, given once a day to patients with mild to moderate hypertension, as well as to assess the 24-hour blood pressure profile with ABPM. METHODS: Initially, 163 patients over 18 were selected, regardless of sex, with blood pressure levels >140/90mmHg at visit 1, which was confirmed at visit 2. One hundred thirty-four patients completed the study. After a 4-week placebo run-in phase, telmisartan 40mg/daily was given for 6 weeks. In those patients whose blood pressure (BP levels were lower than 140/90mmHg, the same dosage was kept for an additional period of 6 weeks. For those who had BP higher than 140/90mmHg, the dosage was increased to 80mg/daily. Sixty-two patients were included in a subgroup that underwent ABPM 3 different times during the study. RESULTS: In the overall group, blood pressure reduction ranged from 162.3±14.5/101.3±5.75 mmHg (baseline to 147.3±20.1/90.8±10.9 mmHg (week 12 (p<0.05. Mean blood pressure decreases were 14.4mmHg for systolic BP and 10.3mmHg for diastolic BP, after 12 weeks of active treatment. A subanalysis showed that 47 (35% patients took telmisartan 40mg throughout the study and 81 (65% had the dosage increased to 80mg daily. Using ABPM, an 8-mmHg reduction in systolic BP as well as a 5-mmHg reduction in diastolic BP were observed, when compared with baseline values in the final 6 hours (18-24 hours after the last dose of study medication. CONCLUSION: Our results confirm that telmisartan given once a day is effective in reducing blood pressure levels in mild to moderate hypertensive patients. This reduction occurs in a sustained and gradual manner during a 24-hour period confirmed by ABPM.

  7. Telmisartan increases fatty acid oxidation in skeletal muscle through a peroxisome proliferator-activated receptor-[gamma] dependent pathway

    Czech Academy of Sciences Publication Activity Database

    Sugimoto, K.; Kazdová, L.; Qi, N.R.; Hyakukoku, M.; Křen, Vladimír; Šimáková, Miroslava; Zídek, Václav; Kurtz, T. W.; Pravenec, Michal

    2008-01-01

    Roč. 26, č. 6 (2008), s. 1209-1215 ISSN 0263-6352 R&D Projects: GA MŠk(CZ) 1M0520; GA MZd(CZ) NR8495; GA MZd NR9359; GA ČR(CZ) GA301/06/0028 Grant - others:-(XE) LSHG-CT-2005-019015; HHMI(US) 55005624; -(US) HL56028; -(US) HL63709 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK ; N - neverejné zdroje Keywords : telmisartan * fatty acid oxidation * PPARgamma Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 5.132, year: 2008

  8. Formulation and evaluation of controlled-release of telmisartan microspheres: In vitro/in vivo study

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2014-12-01

    Full Text Available The aim of this work was to design a controlled-release drug-delivery system for the angiotensin-II receptor antagonist drug telmisartan. Telmisartan was encapsulated with different EUDRAGIT polymers by an emulsion solvent evaporation technique and the physicochemical properties of the formulations were characterized. Using a solvent evaporation method, white spherical microspheres with particle sizes of 629.9–792.1 μm were produced. The in vitro drug release was studied in three different pH media (pH 1.2 for 2 hours, pH 6.8 for 4 hours, and pH 7.4 for 18 hours. The formulations were then evaluated for their pharmacokinetic parameters. The entrapment efficiency of these microspheres was between 58.6% and 90.56%. The obtained microspheres showed good flow properties, which were evaluated in terms of angle of repose (15.29–26.32, bulk and tapped densities (0.37–0.53 and 0.43–0.64, respectively, Carr indices and Hausner ratio (12.94–19.14% and 1.14–1.23, respectively. No drug release was observed in the simulated gastric medium up to 2 hours; however, a change in pH from 1.2 to 6.8 increased the drug release. At pH 7.4, formulations with EUDRAGIT RS 100 showed a steady drug release. The microsphere formulation TMRS-3 (i.e., microspheres containing 2-mg telmisartan gave the highest Cmax value (6.8641 μg/mL at 6 hours, which was three times higher than Cmax for telmisartan oral suspension (TOS. Correspondingly, the area under the curve for TMRS-3 was 8.5 times higher than TOS. Particle size and drug release depended on the nature and content of polymer used. The drug release mechanism of the TMRS-3 formulation can be explained using the Higuchi model. The controlled release of drug from TMRS-3 also provides for higher plasma drug content and improved bioavailability.

  9. Effect of the AT1-receptor antagonists losartan, irbesartan, and telmisartan on angiotensin II-induced facilitation of sympathetic neurotransmission in the rat mesenteric artery

    NARCIS (Netherlands)

    Balt, J. C.; Mathy, M. J.; Nap, A.; Pfaffendorf, M.; van Zwieten, P. A.

    2001-01-01

    SUMMARY: The effect of the AT1-receptor antagonists losartan, irbesartan, and telmisartan on angiotensin II (Ang II)-induced facilitation of noradrenergic neurotransmission was investigated in the isolated rat mesenteric artery under isometric conditions. Electrical field stimulation (2, 4, and 8

  10. The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vogt, Liffert; Navis, Gerjan; Koester, Juergen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

    2005-01-01

    Objective To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized

  11. Determination of telmisartan in human blood plasma: Part II: Liquid chromatography-tandem mass spectrometry method development, comparison to immunoassay and pharmacokinetic study

    NARCIS (Netherlands)

    Hempen, C.M.; Gläsle-Schwarz, Liane; Kunz, Ulrich; Karst, U.

    2006-01-01

    A new liquid chromatography/atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) method with on-line sample clean-up for the determination of telmisartan in human blood plasma is presented. This technique is compared to a previously introduced enzyme-linked immunosorbent

  12. The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vogt, Liffert; Navis, Gerjan; Köster, Jürgen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

    2005-01-01

    To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized study. The

  13. Effect of telmisartan on selected adipokines, insulin sensitivity, and substrate utilization during insulin-stimulated conditions in patients with metabolic syndrome and impaired fasting glucose

    Czech Academy of Sciences Publication Activity Database

    Wohl, P.; Krušinová, E.; Hill, M.; Kratochvílová, S.; Zídková, K.; Kopecký, J.; Neškudla, T.; Pravenec, Michal; Klementová, M.; Vrbíková, J.; Wohl, P.; Mlejnek, Petr; Pelikánová, T.

    2010-01-01

    Roč. 163, č. 4 (2010), s. 573-583 ISSN 0804-4643 R&D Projects: GA MZd(CZ) NR9359; GA MZd(CZ) NS10528 Institutional research plan: CEZ:AV0Z50110509 Keywords : telmisartan * insulin resistance * adipokines Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.482, year: 2010

  14. NEBIVOLOL: A THIRD GENERATION BETA BLOCKER AS ANTIHYPERTENSION AGENT

    Directory of Open Access Journals (Sweden)

    Ni Putu Wirantari

    2013-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Hypertension is a silent killer because it causes complications in vital organs unwitting patients. Beta blockers are generally a choice of safe and effective drugs for initial treatment of hypertension. However, the current hypertension treatment guidelines said beta blockers were not suitable use as first-line therapy because of complications caused. On the use of atenolol found an increased incidence of cardiovascular death of 24%, 14% and cardiac complications 23% cerebrovascular complications. Nebivolol is a third-generation beta-blocker that is highly selective for ?1-adrenergic receptors and has the ability as a direct vasodilator was able to stimulate the activity of endothelial L-arginin/nitric oxide synthase, is expected nebivolol can reduce blood pressure so can achieve blood pressure that expected.

  15. Beta-blockers in cirrhosis and refractory ascites

    DEFF Research Database (Denmark)

    Kimer, Nina; Feineis, Martin; Møller, Søren

    2015-01-01

    with cirrhosis and refractory ascites in a tertiary unit. MATERIAL AND METHODS: We performed a systematic search of literature in May 2014. In addition, 61 patients with cirrhosis and ascites were identified and followed from development of refractory ascites until death or end of follow-up. RESULTS: Fourteen...... trials (9 trials on propranolol, 1 case-control study and 4 retrospective analyses) were identified. One trial suggested an increased mortality in patients treated with beta-blockers and refractory ascites. The results of the remaining trials were inconclusive. No increase in mortality among beta......-blocker-treated patients was found in the present retrospective analysis. CONCLUSIONS: Treatment with beta-blockers may increase mortality in patients with cirrhosis and refractory ascites. However, the current evidence is sparse and high-quality studies are warranted to clarify the matter....

  16. Comparative effects of telmisartan and valsartan as add-on agents for hypertensive patients with morning blood pressure insufficiently controlled by amlodipine monotherapy.

    Science.gov (United States)

    Yoshida, Hideaki; Akasaka, Hiroshi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Miura, Tetsuji

    2014-03-01

    The aim of this study was to determine the efficacies of valsartan and telmisartan as add-on agents for the control of morning blood pressure (BP) in patients already on amlodipine monotherapy. A total of 414 hypertensive patients were prospectively enrolled in a 4-week run-in period when they were treated with amlodipine (5 mg/day), and home BP was measured in the morning and evening. Patients with home systolic BP (SBP) being 135-159 mm Hg in the morning at the end of the run-in period were randomized to additional treatment with valsartan (80 mg/day) or with telmisartan (40 mg/day) for 8 weeks. The primary endpoint was the change in morning home BP, and secondary endpoints included variability of morning home BP. Of the 282 patients randomized, 262 patients (n=131, in each treatment) completed the protocols. Demographic parameters and baseline morning SBP/diastolic BP (DBP) (146.3±7.1/84.8±9.3 vs. 146.0±7.1/84.2±9.1 mm Hg) were comparable in the valsartan group and telmisartan group, and changes in SBP/DBP after 8-week treatment were not significantly different between the two groups (-7.4±10.6/-3.9±6.1 vs. -8.3±9.9/-5.0±5.9 mm Hg). Valsartan significantly increased individual standard deviation and variation coefficient of morning SBP, but telmisartan did not change either of these indices of SBP variation. In subgroups with baseline SBP being above the median (145.2 mm Hg), change in DBP was significantly larger by telmisartan than by valsartan (-6.3±5.6 vs. -3.9±6.7 mm Hg, Pmorning BP in patients on amlodipine monotherapy.

  17. Effect of telmisartan and insulin on endoplasmic reticulum stress and the expression of Sirt1 in testis of type 1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Yan HUANG

    2016-10-01

    Full Text Available Objective  To observe the regulation effect of insulin and telmisartan on the endoplasmic reticulum stress (ERS and the expression of silent information regulator 1 (Sirt1 in the testes of type 1 diabetic rats, and explore the protective effect and mechanism of insulin and telmisartan on the testicular tissue of diabetic rats. Methods  Male Sprague-Dawley (SD rats were randomly divided into normal control group (group A, n=8, diabetic control group (group B, n=8, diabetic treated with insulin group (group C, n=8 and diabetic treated with telmisartan group (group D, n=8. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin. Rats in group C were subcutaneously injected with protamine-zinc insulin once a day, and in group D were given telmisartan once a day by gavage. Only at the end of the eighth week can specimens be taken. And then some tasks were performed such as calculating the testicular weight and testis index, accounting the quantity and activity rate of sperm, detecting the testosterone levels and mRNA expression levels of CCAAT/enhancer binding protein homologous protein (CHOP, glucose regulated protein (GRP-78, cysteine aspartic acid specific protease 12 (caspase-12 and Sirt1. Results  The levels of testosterone, testes weight, sperm counts and motility significantly decreased in group B than in group A (P0.05. The mRNA expression levels of testicular CHOP, GRP-78 and caspase-12 significantly decreased (P0.05. Conclusion  Insulin and telmisartan may play a protective role on testicular tissues by down-regulating the expression of endoplasmic reticulum stress and up-regulating the expression of Sirt1. DOI: 10.11855/j.issn.0577-7402.2016.10.03

  18. Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers.

    Science.gov (United States)

    Oh, Minkyung; Park, Sung-Eun; Ghim, Jong-Lyul; Choi, Young-Kyung; Shim, Eon-Jeong; Shin, Jae-Gook; Kim, Eun-Young

    2017-01-01

    This study compared the pharmacokinetic (PK) and safety profiles of a fixed-dose combination (FDC) formulation of telmisartan and S-amlodipine with those of concomitant administration of the two drugs. This was an open-label, randomized, crossover study in healthy male Koreans. All subjects were administered an FDC tablet containing 40 mg telmisartan and 5 mg S-amlodipine and were also coadministered the same dose of both drugs given separately. The crossover study design included a 14-day washout period between the two treatments. Blood samples were collected up to 168 h following drug administration. The plasma concentrations of telmisartan and S-amlodipine were determined by liquid chromatography tandem mass spectrometry. PK parameters and plasma concentration-time curves were compared. Safety was assessed by measuring vital signs, clinical laboratory tests, physical examinations, and patient interviews. The geometric mean ratios and 90% CIs for the maximum plasma concentration (C max ) and area under the curve from time zero to the last sampling time (AUC t ) were 0.8782 (0.8167-0.9444) and 0.9662 (0.9210-1.0136) for telmisartan and 1.0069 (0.9723-1.0427) and 1.0324 (0.9969-1.0690) for S-amlodipine, respectively. A total of 36 adverse events (AEs) were reported by 23 subjects, but no statistical differences were observed between the two treatments. The most frequently reported AE was a mild-to-moderate headache that was generally self-limiting. For both telmisartan and S-amlodipine, the C max and AUC t 90% CIs were between ln (0.8) and ln (1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar safety profile to the coadministration of these drugs.

  19. The Impact of UPFC on Power Swing Blocker

    DEFF Research Database (Denmark)

    Khodaparast, Jalal; Khederzadeh, M.; Silva, Filipe Miguel Faria da

    2016-01-01

    Power Swing Blocker (PSB) is a complementary part in distance relay that detects power swing in the transmission line to prevent unintended operation of distance relay. Unified Power Flow Controller (UPFC) is used in a transmission line to control active and reactive power. The UPFC operation dur...

  20. Are lipophilic beta-blockers preferable for peri-operative ...

    African Journals Online (AJOL)

    Adele

    coronary artery disease; and it has not been shown to significantly increase pulmonary oedema when administered following acute MI.1. Beta-blockers are protective against sudden arrhythmic death following MI.35-37 The latter accounts for between 22 and. 52% of post MI cardiac deaths.36 37 It is well recognised that the.

  1. Norepinephrine transporter blocker atomoxetine increases salivary alpha amylase

    NARCIS (Netherlands)

    Warren, C.M.; van den Brink, R.L.; Nieuwenhuis, S.; Bosch, J.A.

    It has been suggested that central norepinephrine (NE) activity may be inferred from increases in salivary alpha-amylase (SAA), but data in favor of this proposition are limited. We administered 40mg of atomoxetine, a selective NE transporter blocker that increases central NE levels, to 24 healthy

  2. Attenuation of Cardiovascular response by ß-blocker esmolol during ...

    African Journals Online (AJOL)

    Cardiovascular responses to laryngoscopy and intubation have long been recognized and various efforts have been made to attenuate this response. The aim of this study was to evaluate the efficacy and safety of ß-blocker esmolol in attenuating cardiovascular response to laryngoscopy and tracheal intubation in the ...

  3. Evaluation of nitrendipine -a new calcium channel blocker ...

    African Journals Online (AJOL)

    Nitrendipine (Baypress; Bayer-Miles), a new calcium channel blocker, was administered to 38 hypertensive patients in an oral dose of 20 mg once or twice daily. Both systolic and diastolic blood pressures were reduced to a clinically relevant extent within 2 hours of taking the medication. There was no loss of effect during ...

  4. Calcium channel blockers and cancer risk using the UK CPRD

    NARCIS (Netherlands)

    Grimaldi-Bensouda, Lamiae; De Groot, Mark; Reynolds, Robert; Klungel, Olaf; Rossignol, Michel

    2014-01-01

    Background: This study was part of the Pharmacoepidemiological Research on Outcomes (PROTECT) project which aims at monitoring of the benefit-risk of medicines in Europe. Few epidemiological studies have investigated the association between calcium channel blockers (CCB) and cancer, and have

  5. Beta-Blocker Therapy Early After Myocardial Infarction

    DEFF Research Database (Denmark)

    Pedersen, Susanne Bendesgaard; Nielsen, Jens Cosedis; Bøtker, Hans Erik

    2016-01-01

    BACKGROUND: Beta-blocker (BB) therapy after myocardial infarction (MI) reduces all-cause mortality. OBJECTIVE: The aim of this study was to investigate BB dosing patterns and compliance following MI. METHODS: Using medical patient files and nationwide databases, we identified 100 patients who were...

  6. Evaluation of nitrendipine channel blocker a new calcium

    African Journals Online (AJOL)

    Nitrendipine (Baypress; Bayer-Miles), a new calcium channel blocker, was administered to 38 hypertensive patients in an oral dose of 20 mg once or twice daily. Both systolic and diastolic blood pressures were reduced to a clinically relevant extent within 2 hours of taking the medication. There was no loss of effect during ...

  7. Calcium-channel blockers in pulmonary arterial hypertension.

    Science.gov (United States)

    Chaumais, Marie-Camille; Macari, Elise Artaud; Sitbon, Olivier

    2013-01-01

    Voltage-activated calcium channels are a family of membrane proteins that provide the major influx pathway for calcium in many different types of cells. Calcium-channel blockers inhibit the calcium influx into vascular cells leading to relaxation of smooth muscle cells and vasodilatation. Vasoconstriction of small pulmonary arteries is recognized as a component of the pathogenesis of pulmonary arterial hypertension and treatment with calcium-channel blockers appears to be rational in this setting. No randomized controlled trial has been performed to demonstrate the beneficial effects of calcium-channel blockers in the treatment of patients with pulmonary arterial hypertension. However, uncontrolled studies have suggested that long-term administration of high-dose calcium antagonists dramatically improves survival in a small subset of patients who respond acutely to those drugs, compared with unresponsive patients. The initial response to an acute vasodilator test with inhaled nitric oxide or intravenous prostacyclin or adenosine accurately identifies patients with pulmonary arterial hypertension who are likely to respond to long-term treatment with calcium-channel blockers.

  8. Safe browsing - is an ad-blocker enough?

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    An ad-blocker plugin in your browser stops advertisements and maybe some malware. But is it enough? Are you feeling secure while surfing the Web? If your answer is yes, think twice! What else can you do to protect yourself?

  9. Photochemical fate of beta-blockers in NOM enriched waters

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ling; Xu, Haomin; Cooper, William J. [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States); Song, Weihua, E-mail: wsong@fudan.edu.cn [Department of Environmental Science and Engineering, Fudan University, Shanghai 200433 (China)

    2012-06-01

    Beta-blockers, prescribed for the treatment of high blood pressure and for long-term use after a heart attack, have been detected in surface and ground waters. This study examines the photochemical fate of three beta-blockers, atenolol, metoprolol, and nadolol. Hydrolysis accounted for minor losses of these beta-blockers in the pH range 4-10. The rate of direct photolysis at pH 7 in a solar simulator varied from 6.1 to 8.9 h{sup -1} at pH 7. However, the addition of a natural organic matter (NOM) isolate enhanced the photochemical loss of all three compounds. Indirect photochemical fate, generally described by reactions with hydroxyl radical ({center_dot}OH) and singlet oxygen ({sup 1}{Delta}O{sub 2}), and, the direct reaction with the triplet excited state, {sup 3}NOM{sup Low-Asterisk }, also varied but collectively appeared to be the major loss factor. Bimolecular reaction rate constants of the three beta-blockers with {sup 1}{Delta}O{sub 2} and {center_dot}OH were measured and accounted for 0.02-0.04% and 7.2-38.9% of their loss, respectively. These data suggest that the {sup 3}NOM{sup Low-Asterisk} contributed 50.6-85.4%. Experiments with various {sup 3}NOM{sup Low-Asterisk} quenchers supported the hypothesis that it was singly the most important reaction. Atenolol was chosen for more detailed investigation, with the photoproducts identified by LC-MS analysis. The results suggested that electron-transfer could be an important mechanism in photochemical fate of beta-blockers in the presence of NOM. - Highlights: Black-Right-Pointing-Pointer Photochemical degradation of beta-blockers in the simulated natural waters. Black-Right-Pointing-Pointer Reactive Oxygen Species play a minor role in the indirect photodegradation. Black-Right-Pointing-Pointer The loss of beta-blockers results from direct reaction with {sup 3}DOM{sup Low-Asterisk }.

  10. Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

    Science.gov (United States)

    Chae, Dong Woo; Son, Mijeong; Kim, Yukyung; Son, Hankil; Jang, Seong Bok; Seo, Jeong Min; Nam, Su Youn; Park, Kyungsoo

    2015-10-01

    As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 - 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0-∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ were 0.9262-1.1498, 0.9294-1.0313, and 0.9312-1.0320 for telmisartan, 0.9041-1.0428, 0.9262-1.0085, and 0.9307-1.0094 for rosuvastatin, and 0.8718-1.0022, 0.8901-0.9904, and 0.8872-0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test

  11. Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers

    Directory of Open Access Journals (Sweden)

    Oh M

    2017-12-01

    Full Text Available Minkyung Oh,1,2,* Sung-Eun Park,3,* Jong-Lyul Ghim,1–3 Young-Kyung Choi,1 Eon-Jeong Shim,1–3 Jae-Gook Shin,1–3 Eun-Young Kim1–3 1Department of Pharmacology, 2PharmacoGenomics Research Center, Inje University College of Medicine, Busan, 3Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea *These authors contributed equally to this work Objective: This study compared the pharmacokinetic (PK and safety profiles of a fixed-dose combination (FDC formulation of telmisartan and S-amlodipine with those of concomitant administration of the two drugs.Materials and methods: This was an open-label, randomized, crossover study in healthy male Koreans. All subjects were administered an FDC tablet containing 40 mg telmisartan and 5 mg S-amlodipine and were also coadministered the same dose of both drugs given separately. The crossover study design included a 14-day washout period between the two treatments. Blood samples were collected up to 168 h following drug administration. The plasma concentrations of telmisartan and S-amlodipine were determined by liquid chromatography tandem mass spectrometry. PK parameters and plasma concentration–time curves were compared. Safety was assessed by measuring vital signs, clinical laboratory tests, physical examinations, and patient interviews.Results: The geometric mean ratios and 90% CIs for the maximum plasma concentration (Cmax and area under the curve from time zero to the last sampling time (AUCt were 0.8782 (0.8167–0.9444 and 0.9662 (0.9210–1.0136 for telmisartan and 1.0069 (0.9723–1.0427 and 1.0324 (0.9969–1.0690 for S-amlodipine, respectively. A total of 36 adverse events (AEs were reported by 23 subjects, but no statistical differences were observed between the two treatments. The most frequently reported AE was a mild-to-moderate headache that was generally self-limiting.Conclusion: For both telmisartan and S-amlodipine, the Cmax and AUCt 90% CIs

  12. Evaluation of safety and efficacy of telmisartan-amlodipine combination in treating hypertension.

    Science.gov (United States)

    Faruqui, Arif A

    2008-09-01

    The objective of this open, non-comparative, prospective postmarketing surveillance (PMS) study was to identify, validate and quantify the safety and efficacy associated with the use of fixed dose combination (FDC) of telmisartan 40 mg + amlodipine 5 mg (T40+A5) in hypertensive patients with or without concomitant diabetes. The data was collected from 72 centres from all over India during the period of June 2007 to February 2008. A total of 251 patients of either sex and those who were newly diagnosed stage II hypertension, or those who were uncontrolled on monotherapy with or without diabetes mellitus were included in this study. Patients were prescribed with T40+A5 combination orally. Systolic BP (SBP), diastolic BP (DBP) and heart rate (HR) were measured at the start and at the end of 2, 4 and 8 weeks of treatment. Primary efficacy end points were reduction in clinical SBP/ DBP from baseline to study end and number of patients achieving JNC VII goals. Tolerability was assessed by treatment-emergent adverse events. Out of 251 patients, 208 patients had completed the study (120 males and 88 females), 42 were lost to follow-up the study and one patient was withdrawn due to adverse effects. The mean age of the patients was 54.5 +/- 0.98 years for males and 52.94 +/- 1.078 years for females. Diabetes mellitus was seen in 64.9% of cases, dyslipidaemia in 2.88%, previous IHD in 7.2% cases and chronic obstructive pulmonary disease (COPD) in 0.50% of cases. Reduction in the mean SBP was found to be 12.08%, 18.92% and 22.90% at the end of 2, 4 and 8 weeks respectively (p hypertensive patients and 70% diabetic hypertensive patients achieved the JNC VII recommended goals. The overall incidence of ADRs was 7.69% with headache (1.92%) and vertigo (1.44%), as the commonest side-effect. According to physician's assessment of efficacy and tolerability 99.5% of total cases showed good to excellent response. In the treatment of stage II hypertensive patient the FDC of T40+A5

  13. Effectiveness of angiotensin II receptor antagonists in a cohort of Dutch patients with type 2 diabetes mellitus (ZODIAC-14).

    Science.gov (United States)

    van Hateren, Kornelis J J; Landman, Gijs W D; Groenier, Klaas H; Bilo, Henk J G; Kleefstra, Nanne

    2015-04-01

    There is limited evidence with respect to the between-group effects of various angiotensin receptor blockers (ARBs) on blood pressure and albuminuria in patients with type 2 diabetes mellitus. Therefore, we aimed to investigate the effects of differing ARBs on systolic blood pressure (SBP) and the albumin-creatinine ratio after 1 year in a large cohort of patients with type 2 diabetes mellitus. In 2007, 24 940 primary care patients with type 2 diabetes mellitus participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study, a prospective observational cohort study. Patients were included in the current study if they were prescribed an ARB in 2007 and if 1-year follow-up data were available. The final study population comprised 3610 patients. Multivariate mixed-model analyses were performed to estimate effects of the various ARBs on SBP and albuminuria. Stratified subgroup analyses were performed according to baseline hypertension and albuminuria. SBP decreased in all groups, the largest decrease being observed in the group receiving telmisartan. No significant or relevant changes over time were observed among groups for SBP and albuminuria. In the subgroup (n=1225) of normotensive patients, telmisartan was associated with a larger decrease in SBP after 1 year compared to other ARBs, without different effects on the albumin-creatinine ratio. We observed no differences in effects on SBP and the albumin-creatinine ratio among differing ARBs in patients with type 2 diabetes mellitus. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  14. Pre-stroke use of beta-blockers does not affect ischaemic stroke severity and outcome

    NARCIS (Netherlands)

    De Raedt, S.; Haentjens, P.; De Smedt, A.; Brouns, R.; Uyttenboogaart, Maarten; Luijckx, G. J.; De Keyser, J.

    Background and purpose: It is unclear whether pre-stroke beta-blockers use may influence stroke outcome. This study evaluates the independent effect of pre-stroke use of beta-blockers on ischaemic stroke severity and 3 months functional outcome. Methods: Pre-stroke use of beta-blockers was

  15. Combinational approach using solid dispersion and semi-solid matrix technology to enhance in vitro dissolution of telmisartan

    Directory of Open Access Journals (Sweden)

    Syed Faisal Ali

    2016-02-01

    Full Text Available The present investigation was focused to formulate semi-solid capsules (SSCs of hydrophobic drug telmisartan (TLMS by encapsulating semi-solid matrix of its solid dispersion (SD in HPMC capsules. The combinational approach was used to reduce the lag time in drug release and improvise its dissolution. SDs of TLMS was prepared using hot fusion method by varying the combinations of Pluronic-F68, Gelucire 50/13 and Plasdone S630. A total of nine batches (SD1-SD9 were characterized for micromeritic properties, in vitro dissolution behavior and surface characterization. SD4 with 52.43% cumulative drug release (CDR in phosphate buffer, pH 7.4, in 120 min, t50% 44.2 min and DE30min 96.76% was selected for the development of semi-solid capsules. Differential scanning calorimetry of SD4 revealed molecular dispersion of TLMS in Pluronic-F68. SD4 was formulated into SSCs using Gelucire 44/14 and PEG 400 as semi-solid components and PEG 6000 as a suspending agent to achieve reduction in lag time for effective drug dissolution. SSC6 showed maximum in vitro drug dissolution 97.49 % in phosphate buffer, pH 7.4 with in 20 min that was almost a three folds reduction in the time required to achieve similar dissolution by SD. Thus, SSCs present an excellent approach to enhance in vitro dissolution as well as to reduce the lag time of dissolution for poorly water soluble drugs especially to those therapeutic classes that are intended for faster onset of action. Developed approach based on HPMC capsules provided a better alternative to target delivery of telmisartan to the vegetarian population.

  16. HEART FAILURE, DIABETES, BETA-BLOCKERS AND RISK OF HYPOGLYCEMIA

    Directory of Open Access Journals (Sweden)

    A. A. Aleksandrov

    2008-01-01

    Full Text Available Aim. To evaluate an influence of carvedilol on risk of hypoglycemia in patients with diabetes type 2 (D2 and chronic heart failure (CHF treated with angiotensin converting enzyme (ACE inhibitors.Material and methods. 13 patients (10 men, 3 women; aged 59,8±6,7 y.o. with D2 and CHF caused by ischemic heart disease were included in the study. Before inclusion all patients were treated with ACE inhibitors and various beta-blockers (atenolol, metoprolol, bisoprolol. These beta-blockers were changed for carvedilol. Heart ultrasonography, blood pressure control, glycemia monitoring, HbA1c level determination were performed before, during and after carvedilol therapy.Results. Carvedilol reduces frequency and duration of hypoglycaemia episodes. There were not episodes of severe hypoglycaemia during carvedilol therapy.Conclusion. Carvedilol reduces risk of hypoglycemia when it is used in combination with ACE inhiditors in diabetic patients with CHF.

  17. Use of β-Blockers in Pulmonary Hypertension.

    Science.gov (United States)

    Perros, Frédéric; de Man, Frances S; Bogaard, Harm J; Antigny, Fabrice; Simonneau, Gérald; Bonnet, Sébastien; Provencher, Steeve; Galiè, Nazzareno; Humbert, Marc

    2017-04-01

    Contrasting with the major attention that left heart failure has received, right heart failure remains understudied both at the preclinical and clinical levels. However, right ventricle failure is a major predictor of outcomes in patients with precapillary pulmonary hypertension because of pulmonary arterial hypertension, and in patients with postcapillary pulmonary hypertension because of left heart disease. In pulmonary hypertension, the status of the right ventricle is one of the most important predictors of both morbidity and mortality. Paradoxically, there are currently no approved therapies targeting the right ventricle in pulmonary hypertension. By analogy with the key role of β-blockers in the management of left heart failure, some authors have proposed to use these agents to support the right ventricle function in pulmonary hypertension. In this review, we summarize the current knowledge on the use of β-blockers in pulmonary hypertension. © 2017 American Heart Association, Inc.

  18. Analysis of solar blocker through portable X-ray fluorescence

    International Nuclear Information System (INIS)

    Ferreira, Diego de Dio; Melquiades, Fabio Luiz; Appoloni, Carlos Roberto; Lopes, Fabio; Lonni, Audrey Stinghen G.; Oliveira, Frederico Minardi de; Duarte, Jose C.

    2009-01-01

    This paper estimates the concentration of TiO 2 by Energy Dispersion X-ray fluorescence (EDXRF) viewing t obtain the FPS due to the physical barrier in the composition of solar blockers, and identifies possible present metals in the samples. A portable EDXRF equipment was used and 27 commercial of different brands and solar protection factors were analysed. Also, three formulations (A, B and C) were prepared and measured estimated in FPS-30 using 5% or TiO 2 . The quantification was performed through calibration curves with 1% to 30% standards of TiO 2 . As result, it was possible to determine the contribution to physical protection in the FPS, associated to the Ti concentration present in some solar blocker samples available in the market. Also, it was possible to detect the presence of various metals in solar protectors, such as Fe, Zn, Br and Sr, and identify chemical elements which were not mentioned and their formulation as well

  19. Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Guo Zhixin

    2012-08-01

    Full Text Available Abstract Background Diabetic cardiovascular disease is associated with decreased adiponectin and increased oxidative stress. This study investigated the effect of telmisartan on the expression of adiponectin receptor 2 (adipoR2 and nicotinamide adenine dinucleotide phosphate (NADPH oxidase subunits in the heart and the expression of adiponectin receptor 1 (adipoR1 in aorta in type 2 diabetic rats. Methods Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ. Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4, monocyte chemoattractant protein-1(MCP-1 and connective tissue growth factor (CTGFin the heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-κB in aorta were analyzed in controls and diabetic rats treated with or without telmisartan (5mg/kg/d by gavage for 12 weeks. Results Heart function, plasma and myocardial adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were significantly decreased in diabetic rats (P Conclusions Our results suggest that telmisartan upregulates the expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously, it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF, contributing so to the improvement of heart function in diabetic rats. Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-κB in the abdominal aorta in diabetic rats.

  20. Microalbuminuria and sRAGE in High-Risk Hypertensive Patients Treated with Nifedipine/Telmisartan Combination Treatment: A Substudy of TALENT

    Directory of Open Access Journals (Sweden)

    Colomba Falcone

    2012-01-01

    Full Text Available Some antihypertensive drugs have also renoprotective and anti-inflammatory properties that go beyond their effect on blood pressure. It has been suggested that microalbuminuria and glomerular filtration rate (GFR are associated with circulating levels of the soluble form of the receptor, sRAGE (soluble receptor for advanced glycation ends-products. In the present analysis, we used data from the TALENT study to evaluate soluble receptor for advanced glycation end-products (sRAGE plasma levels in patients with hypertension and high-cardiovascular risk-treated nifedipine and telmisartan in combination. Treatment with nifedipine-telmisartan significantly decreased mean systolic and diastolic ambulatory blood pressure and resulted in a significant increase in sRAGE plasma concentrations after 24 weeks of therapy. We concluded that in hypertensive patients with early-stage renal disease, sRAGE concentrations are not influenced by either microalbuminuria or GFR. Long-term treatment with a combination of nifedipine-telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus exerting an atheroprotective and anti-inflammatory activity.

  1. Effect of telmisartan on arterial distensibility and central blood pressure in patients with mild to moderate hypertension and Type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Roland Asmar

    2001-06-01

    Full Text Available Arterial wall stiffness is an important independent risk factor for cardiovascular disease in hypertensive patients, which is further exacerbated by co-existent diabetes mellitus. Increased arterial stiffness is directly associated with an increase in pulse wave velocity (PWV and indirectly with increased central and peripheral blood pressure. Following a two-week placebo run-in period, 27 patients with mild to moderate essential hypertension and Type 2 diabetes mellitus, were randomised to once daily treatment with either telmisartan 40 mg or placebo for three weeks, and after a two-week washout period, crossed-over to the alternative treatment for a further three weeks. Carotid/femoral and carotid/radial PWV were measured non-invasively using the automatic Complior® device, and central parameters (central blood pressure, pulse contour analysis, and augmentation index were measured using the SphygmoCor® system, at the start and end of each treatment period. Compared with placebo, treatment with telmisartan significantly reduced carotid/femoral PWV (mean adjusted treatment difference -0.95 m/s, 95% confidence intervals: -1.67, -0.23 m/s, p=0.013, as well as peripheral and central diastolic, systolic and pulse pressure. In conclusion, the results of this study show that telmisartan is effective in reducing arterial stiffness in hypertensive patients with Type 2 diabetes mellitus, and may potentially have beneficial effects on cardiovascular outcomes, beyond blood-pressure lowering effects, in this patient group.

  2. Prevalence of diabetic nephropathy in Type 2 Diabetes Mellitus in rural communities of Guanajuato, Mexico. Effect after 6 months of Telmisartan treatment.

    Science.gov (United States)

    Zenteno-Castillo, Priscyla; Muñoz-López, Daniela Beatriz; Merino-Reyes, Benjamín; Vega-Sánchez, Ángel; Preciado-Puga, Monica; González-Yebra, Ana Lilia; Kornhauser, Carlos

    2015-12-01

    To determine the prevalence of Diabetic Nephropathy (DN) in patients with type 2 Diabetes Mellitus (T2DM) with over 5 years of evolution in rural communities of Guanajuato, Mexico, and evaluate the effects of an ARB treatment over 6 months in patients with DN. Patients of both sexes, 38-86 years, T2DM over 5 years of evolution and diagnosed with arterial hypertension (HT) after T2DM incidence. Monthly determination of microalbuminuria (MA), lipids, glucose, serum creatinine, and glycated hemoglobin (HbA1c). Estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula. A dose of 80 mg of Telmisartan was administered daily over 6 months. The total adult population of two rural communities (3609 subjects) was studied, 335 subjects had T2DM, among them 80 (with a prevalence of 24%) had DN and HT. Sixty-seven patients received Telmisartan, and showed significant improvement in all parameters studied. A higher prevalence of DN than that reported in the Mexican National Health Survey (ENSANUT) was found. Further research is required in a larger population sample in order to confirm the results of Telmisartan treatment.

  3. Stress degradation studies of Telmisartan and Metoprolol extended release tablets by a validated stability indicating reverse phase-high performance liquid chromatography method

    Directory of Open Access Journals (Sweden)

    Kabeer Ahmed Shaikh

    2014-01-01

    Full Text Available Background and Aim: A sensitive reverse phase high-performance liquid chromatographic method has been developed for the simultaneous determination of Telimisartan and Metoprolol in tablet dosage form. Materials and Method: The chromatographic separation was achieved on Inertsil ODS 3V, 150 x 4.6 mm, 5μ analytical column. Mobile phase consisting of mobile phase A- 0.05M sodium dihydrogen phosphate buffer pH 3.0 and mobile phase B-Acetonitrile, with gradient program time in min /Mobile phase B% 0/22, 4/45, 6/45,18/22, 20/22. Detector was set at 222nm. Results and Conclusion: The described method shows excellent linearity over a range of 80-2 μg mL−1 for Telmisartan and 100-4 μg mL−1 for Metoprolol. The correlation coefficient for Telmisartan is 0.9998 and Metoprolol is 0.9999. The proposed method was found to be suitable for determination of Telmisartan and Metoprolol in tablet dosage form. Forced degradation of the drug product was conducted in accordance with the ICH guideline. Acidic, basic, hydrolytic, oxidative, thermal and photolytic degradation was used to assess the stability indicating power of the method. The drug product was found to be stable in acid, oxidation, thermal and photolytic stress condition and found degradation in base hydrolysis stress condition.

  4. [Critically appraised article].

    Science.gov (United States)

    Neumann, Ignacio; Grassi, Bruno

    2012-01-01

    Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. The trial ran from 2001 to 2007. After a 3-week run-in period, 25,620 participants were randomly assigned to ramipril 10 mg a day (n = 8,576), telmisartan 80 mg a day (n = 8,542), or to a combination of both drugs (n = 8,502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n = 1,147 [13.4%]) and ramipril (1,150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1,233 [14.5%]; HR 1.09, 1.01-1.18, p = 0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%];HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24,1.01-1.51, p = 0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m² vs -4.12 [17.4], p proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.

  5. Effects of stimulation of soluble guanylate cyclase on diabetic nephropathy in diabetic eNOS knockout mice on top of angiotensin II receptor blockade.

    Directory of Open Access Journals (Sweden)

    Ina M Ott

    Full Text Available The prevalence of diabetes mellitus and its complications, such as diabetic nephropathy (DN, is rising worldwide and prevention and treatment are therefore becoming increasingly important. Therapy of DN is particularly important for patients who do not adequately respond to angiotensin receptor blocker (ARB treatment. Novel approaches include the stimulation of soluble guanylate cyclase (sGC as it is reported to have beneficial effects on cardiac and renal damage. We aimed to investigate the effects of the sGC stimulator riociguat and ARB telmisartan on kidney function and structure in a hypertensive model of diabetic nephropathy. Seventy-six diabetic male eNOS knockout C57BL/6J mice were randomly divided after having received streptozotocin: telmisartan (1 mg/kg/d, riociguat (3 mg/kg/d, riociguat+telmisartan (3+1 mg/kg/d, and vehicle. Fourteen mice were used as non-diabetic controls. Treatment duration was 11 weeks. Glucose concentrations were increased and similar in all diabetic groups. Telmisartan insignificantly reduced blood pressure by 5.9 mmHg compared with diabetic controls (111.2±2.3 mmHg vs. 117.1±2.2 mmHg; p = 0.071. Treatment with riociguat both alone and in combination with telmisartan led to a significant reduction of blood pressure towards diabetic vehicle (105.2±2.5 mmHg and 105.0±3.2 mmHg, respectively, vs. 117.1±2.2 mmHg. Combined treatment also significantly decreased albuminuria compared with diabetic controls (47.3±9.6 µg/24 h vs. 170.8±34.2 µg/24 h; p = 0.002 reaching levels similar to those of non-diabetic controls (34.4±10.6 µg/24 h, whereas the reduction by single treatment with either telmisartan (97.8±26.4 µg/24 h or riociguat (97.1±15.7 µg/24 h was not statistically significant. The combination treatment led to a significant (p<0.01 decrease of tissue immunoreactivity of malondialdehyde, as consequence of reduced oxidative stress. In conclusion, stimulation of sGC significantly reduced urinary

  6. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials

    DEFF Research Database (Denmark)

    Bilous, Rudy; Chaturvedi, Nish; Sjølie, Anne Katrin

    2009-01-01

    BACKGROUND: Microalbuminuria in diabetes is strongly predictive of nephropathy, end-stage renal disease, and premature cardiovascular morbidity and mortality. Effective preventive therapies are therefore a clinical priority. OBJECTIVE: To determine whether the angiotensin-receptor blocker candesa...

  7. The effects of dual and triple combinations of trandolapril, telmisartan, and verapamil on overt proteinuria in the patients with diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Bülent Albayrak

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is one of the most important causes of the end-stage renal failure and its prevalence is found to be increasing. The presence of hypertension and progressive proteinuria is among the important findings. In this study, the effects of double and triple combinations of trandolapril, telmisartan, and verapamil on proteinuria were investigated in diabetic patients with nephropathy. Seventy-eight patients (mean age: 56.11 ± 11.26 years; 47 females and 31 males with overt proteinuria and DN were included in this study. The patients were divided into four groups: Group I (n: 18, trandolapril + telmisartan, Group II (n: 20, trando- lapril + verapamil, Group III (n: 20, trandolapril +telmisartan + verapamil, and Group IV (n: 20, telmisartan + verapamil. At the end of a three-month therapy, within and between group compa- risons were done about the effects of the use of double or triple drug combinations on proteinuria, glomerular filtration rate (GFR, electrolytes, serum albumin, low-density lipoprotein (LDL- cholesterol, and HbA1C. There was no significant difference among groups in terms of age, gender, diabetes duration, body mass index, and retinopathy frequency. The decreases in protei- nuria and mean arterial blood pressure (MABP were significant in all groups. The decrease in proteinuria was independent of the decrease in MABP [the reduction rate in proteinuria was 39% (P <0.001 in Group I, 37% (P <0.001 in Group II, 42% (P <0.001 in Group III, and 43% (P <0.001 in Group IV; the reduction rate in MABP was 10.6% (P <0.001 in Group I, 13.7% (P <0.001 in Group II, 17.5% (P <0.001 in Group III, and 15.4% (P <0.001 in Group IV]. Decrease in HbA1C (before and after treatment was significant in Groups III and IV when com- pared to Groups I and II. Any adverse event, like hyperkalemia, was not observed. There was no significant difference among the groups in terms of GFR, LDL-cholesterol, albumin, and potassium. All the patients

  8. Increased serum potassium affects renal outcomes

    DEFF Research Database (Denmark)

    Miao, Y; Dobre, D; Heerspink, H J Lambers

    2011-01-01

    To assess the effect of an angiotensin receptor blocker (ARB) on serum potassium and the effect of a serum potassium change on renal outcomes in patients with type 2 diabetes and nephropathy.......To assess the effect of an angiotensin receptor blocker (ARB) on serum potassium and the effect of a serum potassium change on renal outcomes in patients with type 2 diabetes and nephropathy....

  9. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial

    DEFF Research Database (Denmark)

    Diener, Hans-Christoph; Sacco, Ralph L; Yusuf, Salim

    2008-01-01

    telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. METHODS: Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER......-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed...... of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically...

  10. Beta-Blocker Therapy and Hemophagocytic Lymphohistiocytosis: A Case Report

    Directory of Open Access Journals (Sweden)

    C. Müller

    2010-01-01

    as indicated by high lactate dehydrogenase and alanine aminotransferase levels. A therapeutic switch from propranolol to the 1-receptor blocker metoprolol appeared to be instrumental in hemodynamic improvement and allowed discharge from hospital. However, the infant ultimately died from secondary inflammatory reactivation and intractable pulmonary obstructive disease. The autopsy results revealed HLH. Conclusion. Our case describes HLH secondary to heart failure and Downs syndrome. In this highly activated inflammatory state the beneficial hemodynamic effects of propranolol may be accompanied by immunomodulatory effects and the risk of acute liver failure. HLH occurs with a distinct pathophysiology, and specific treatment might be mandatory to increase the chance of survival.

  11. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache.

    Directory of Open Access Journals (Sweden)

    Jeffrey L Jackson

    Full Text Available To compare the effectiveness and side effects of migraine prophylactic medications.We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models.PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014.We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration.Placebo controlled trials included alpha blockers (n = 9, angiotensin converting enzyme inhibitors (n = 3, angiotensin receptor blockers (n = 3, anticonvulsants (n = 32, beta-blockers (n = 39, calcium channel blockers (n = 12, flunarizine (n = 7, serotonin reuptake inhibitors (n = 6, serotonin norepinephrine reuptake inhibitors (n = 1 serotonin agonists (n = 9 and tricyclic antidepressants (n = 11. In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82, -flunarizine (-1.1 headaches/month (ha/month, 95% CI: -1.6 to -0.67, fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17, metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46, pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21, propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62, topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73 and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8. Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril, two angiotensin receptor blockers (candesartan, telmisartan, two anticonvulsants (lamotrigine, levetiracetam, and several beta-blockers (atenolol, bisoprolol, timolol. Network meta-analysis found amitriptyline to be better than several other medications including candesartan, fluoxetine, propranolol, topiramate and valproate and no different than

  12. A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache

    Science.gov (United States)

    2015-01-01

    Objective To compare the effectiveness and side effects of migraine prophylactic medications. Design We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models. Data Sources PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014. Eligibility Criteria for Selecting Studies We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration. Results Placebo controlled trials included alpha blockers (n = 9), angiotensin converting enzyme inhibitors (n = 3), angiotensin receptor blockers (n = 3), anticonvulsants (n = 32), beta-blockers (n = 39), calcium channel blockers (n = 12), flunarizine (n = 7), serotonin reuptake inhibitors (n = 6), serotonin norepinephrine reuptake inhibitors (n = 1) serotonin agonists (n = 9) and tricyclic antidepressants (n = 11). In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82), -flunarizine (-1.1 headaches/month (ha/month), 95% CI: -1.6 to -0.67), fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17), metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46), pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21), propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62), topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73) and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8). Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril), two angiotensin receptor blockers (candesartan, telmisartan), two anticonvulsants (lamotrigine, levetiracetam), and several beta-blockers (atenolol, bisoprolol, timolol). Network meta-analysis found amitriptyline to be better than several other medications including

  13. The association of Raynaud syndrome with β-blockers: a meta-analysis.

    Science.gov (United States)

    Mohokum, Melvin; Hartmann, Peter; Schlattmann, Peter

    2012-10-01

    Vasospastic disorders of the digital circulation such as the Raynaud syndrome (RS) are known side effects of treatment of β-adrenergic blockade. The prevalence of RS in patients during treatment with β-blockers is not well defined. The objective of this meta-analysis is to assess the prevalence of RS in patients receiving β-blockers. A literature search was performed for studies dealing with RS and patients receiving β-blockers. The studies provided sufficient data to estimate the prevalence of RS in patients receiving β-blockers. A total of 13 eligible studies, contributing data on 1012 individuals, were included in this meta-analysis. For RS in patients receiving β-blockers, a pooled prevalence of 14.7% (95% confidence interval 0.076-0.236) were obtained. Statistically publication bias was not present (P = .877). Despite some heterogeneity, there is a possible indication of an association between RS and patients receiving β-blockers.

  14. A comparative study on the effectiveness of losartan/hydrochlorothiazide and telmisartan/hydrochlorothiazide in patients with hypertension.

    Science.gov (United States)

    Hamada, Toshihiro; Kuwabara, Masanari; Watanabe, Arisa; Mizuta, Einosuke; Ohtahara, Akira; Omodani, Hiroki; Watanabe, Masashi; Nakamura, Hiroki; Hirota, Yutaka; Miyazaki, Satoshi; Kato, Masahiko; Ogino, Kazuhide; Kosaka, Hiroki; Haruaki, Ninomiya; Taniguchi, Shin-ichi; Yamamoto, Kazuhiro; Kotake, Hiroshi; Hisatome, Ichiro

    2014-01-01

    Long-term effects of a low-dose hydrochlorothiazide (HCTZ) with losartan (LOS) on uric acid (UA) metabolism as well as glucose metabolism have been studied in hypertensive patients in comparison with those of a low-dose HCTZ with telmisartan (TEL). Fifty-nine hypertensive patients were allocated to a combination therapy with either losartan (50 mg/day)/HCTZ (12.5 mg/day) (LOS + HCTZ group: n = 37) or telmisartan (40 mg/day)/HCTZ (12.5 mg/day) (TEL + HCTZ group: n = 22), respectively. Before and 1 year after the treatment, blood pressure and biochemical parameters of blood and urine were evaluated. Both systolic and diastolic blood pressures significantly decreased in two groups, without any statistical differences among them. LOS + HCTZ caused no changes in the serum UA level or the ratio of UA clearance to creatinine clearance (CUA/Ccr), whereas TEL + HCTZ significantly increased the serum UA level and reduced CUA/Ccr. LOS + HCTZ did not influence CUA/Ccr in patients with their serum UA below 5.4 mg/dl, while LOS + HCTZ significantly increased CUA/Ccr in patients with their serum UA above 5.5 mg/dl. TEL + HCTZ significantly reduced CUA/Ccr in patients with their serum UA below and above 5.4 mg/dl to increase serum UA level significantly. Neither combination therapies caused any changes in fasting plasma glucose, HbA1c and HOMA-R. In patients with their serum UA level above 5.4 mg/dl, TEL + HCTZ increased HOMA-R, whereas LOS + HCTZ did not. LOS + HCTZ did not influence UA metabolism as well as glucose metabolism, likely because of inhibitory action of losartan on URAT1, although TEL + HCTZ were accompanied with impairment of the UA metabolism and glucose metabolism.

  15. Effects of salt supplementation on the albuminuric response to telmisartan with or without hydrochlorothiazide therapy in hypertensive patients with type 2 diabetes are modulated by habitual dietary salt intake.

    Science.gov (United States)

    Ekinci, Elif I; Thomas, Georgina; Thomas, David; Johnson, Cameron; Macisaac, Richard J; Houlihan, Christine A; Finch, Sue; Panagiotopoulos, Sianna; O'Callaghan, Chris; Jerums, George

    2009-08-01

    OBJECTIVE This prospective randomized double-blind placebo-controlled crossover study examined the effects of sodium chloride (NaCl) supplementation on the antialbuminuric action of telmisartan with or without hydrochlorothiazide (HCT) in hypertensive patients with type 2 diabetes, increased albumin excretion rate (AER), and habitual low dietary salt intake (LDS; 200 mmol sodium/24 h on two of three consecutive occasions). RESEARCH DESIGN AND METHODS Following a washout period, subjects (n = 32) received 40 mg/day telmisartan for 4 weeks followed by 40 mg telmisartan plus 12.5 mg/day HCT for 4 weeks. For the last 2 weeks of each treatment period, patients received either 100 mmol/day NaCl or placebo capsules. After a second washout, the regimen was repeated with supplements in reverse order. AER and ambulatory blood pressure were measured at weeks 0, 4, 8, 14, 18, and 22. RESULTS In LDS, NaCl supplementation reduced the anti-albuminuric effect of telmisartan with or without HCT from 42.3% (placebo) to 9.5% (P = 0.004). By contrast, in HDS, NaCl supplementation did not reduce the AER response to telmisartan with or without HCT (placebo 30.9%, NaCl 28.1%, P = 0.7). Changes in AER were independent of changes in blood pressure. CONCLUSIONS The AER response to telmisartan with or without HCT under habitual low salt intake can be blunted by NaCl supplementation. By contrast, when there is already a suppressed renin angiotensin aldosterone system under habitual high dietary salt intake, the additional NaCl does not alter the AER response.

  16. Self-reported and actual beta-blocker prescribing for heart failure patients: physician predictors.

    Directory of Open Access Journals (Sweden)

    Sanjai Sinha

    2009-12-01

    Full Text Available Beta-blockers reduce mortality among patients with systolic heart failure (HF, yet primary care provider prescription rates remain low.To examine the association between primary care physician characteristics and both self-reported and actual prescription of beta-blockers among patients with systolic HF.Cross-sectional survey with supplementary retrospective chart review.Primary care providers at three New York City Veterans Affairs medical centers.MAIN OUTCOMES WERE: 1 self-reported prescribing of beta-blockers, and 2 actual prescribing of beta-blockers among HF patients. Physician HF practice patterns and confidence levels, as well as socio-demographic and clinical characteristics, were also assessed.Sixty-nine of 101 physicians (68% completed the survey examining self-reported prescribing of beta-blockers. Physicians who served as inpatient ward attendings self-reported significantly higher rates of beta-blocker prescribing among their HF patients when compared with physicians who did not attend (78% vs. 58%; p = 0.002, as did physicians who were very confident in managing HF patients when compared with physicians who were not (82% vs. 68%; p = 0.009. Fifty-one of these 69 surveyed physicians (74% were successfully matched to 287 HF patients for whom beta-blocker prescribing data was available. Physicians with greater self-reported rates of prescribing beta-blockers were significantly more likely to actually prescribe beta-blockers (p = 0.02; however, no other physician characteristics were significantly associated with actual prescribing of beta-blockers among HF patients.Physician teaching responsibilities and confidence levels were associated with self-reported beta-blocker prescribing among their HF patients. Educational efforts focused on improving confidence levels in HF care and increasing exposure to teaching may improve beta-blocker presciption in HF patients managed in primary care.

  17. Beta-blockers and depression in elderly hypertension patients in primary care.

    Science.gov (United States)

    Ringoir, Lianne; Pedersen, Susanne S; Widdershoven, Jos W M G; Pouwer, Francois; Keyzer, Josephine M L; Romeijnders, Arnold C; Pop, Victor J M

    2014-06-01

    Previous findings regarding a possible association between beta-blocker use and depression are mixed. To our knowledge there have been no studies investigating the association of beta-blockers with depression in primary care hypertension patients without previous myocardial infarction. The aim of this study was to determine the relation between lipophilic beta-blocker use and depression in elderly primary care patients with hypertension. This was a cross-sectional study in primary care practices located in the South of The Netherlands. Primary care hypertension patients without previous myocardial infarction or heart failure (n=573), aged between 60 and 85 years (mean age=70±6.6), were included. All patients underwent a structured interview that included a self-report questionnaire to assess depression (PHQ-9), which was divided in four groups (PHQ-9 score of 0, 1--3, 4--8, 9 or higher). A PHQ-9 score of 0 was more prevalent in non-beta-blocker users versus lipophilic beta-blocker users (46% versus 35%), a PHQ-9 score of 4--8 was less prevalent in non-beta-blocker users as compared with lipophilic beta-blocker users (14% versus 25%). A chi-squared test showed that lipophilic beta-blocker users as compared to non-beta-blockers users were more likely to be in a higher depression category. Ordinal regression showed a significant relationship between use of lipophilic beta-blockers and depression (OR=1.60, 95% CI=1.08--2.36) when adjusting for potential confounders. Our findings show that primary care hypertension patients who use a lipophilic beta-blocker are more likely to have higher depression scores than those who do not use a lipophilic beta-blocker.

  18. Effects of beta-blockers and nicardipine on oxotremorine-induced tremor in common marmosets.

    Science.gov (United States)

    Mitsuda, M; Nomoto, M; Iwata, S

    1999-10-01

    Effects of beta-blockers (propranolol, arotinolol and nipradilol) and a Ca2+ channel blocker (nicardipine) on oxotremorine-induced tremor were studied in common marmosets. Generalized tremor was elicited by an intraperitoneal administration of 0.25 mg/kg oxotremorine. Intensity of the tremor was classified into 7 degrees, and it was evaluated every 10 min. The total intensity of oxotremorine-induced tremor for each drug was expressed as "points", which were the sum of tremor intensity scores evaluated every 10 min up to 190 min following the administration of oxotremorine. Beta-blockers significantly suppressed the tremor. On the other hand, the Ca2+ channel blocker exacerbated the tremor.

  19. The Comparison α-Blocker+M3 Selective Anti-Muscarinic Combined Therapy And α-Blocker Monotherapy

    Directory of Open Access Journals (Sweden)

    Serkan Doğan

    2012-01-01

    Full Text Available Aim: Effectiveness and reliability comparison of alpha-blocker monotherapy (doksazosin and combined alpha-blocker M3 selective antimuscarinic (doksazosin darifenacin treatments on male patients with Benign prostate hyperplasia and accompanying OAB (overactive bladder symptoms. Material and Method: 101 patients with ages 50 and above who had LUTS (Lower urinary tract symptoms complaints were included in the study. Patients were randomly organized into two groups. One group had treatment with 4mg doksazosin, the other group had 4mg doksazosin combined with 7.5mg darifenacin. Patients were evaluated in accordance with BPH manuals of EUA (European Urology Association and AUA (American Urology Association. Patients were re-evaluated on 12th week after the treatment. International prostate symptom scores (IPSS, IPSS quality of life scores (IPSS-QoL, maximum urine flow rate (Qmax, average urine flow rates (AFR and PVR (Post Voiding Residual Volume data were obtained before and after the treatment from all patients. Results: Patients who received combined treatment had experienced considerable drop (p

  20. THE ROLE OF S-AMLODIPINE IN ARTERIAL HYPERTENSION THERAPY WITH COMBINATION OF CALCIUM CHANNEL BLOCKERS AND BETA-BLOCKERS

    Directory of Open Access Journals (Sweden)

    M. A. Maksimova

    2013-01-01

    Full Text Available Aim. To study efficacy and safety of calcium channel blocker, S-amlodipine, in combination with β-blocker, atenolol, in patients with arterial hypertension (HT 1-2 degree com- pared to fixed combination of racemic amlodipine and atenolol.Material and methods. Patients (n=31, 7 men and 24 women with HT 1–2 degree were included into the study. The patients were randomized into two groups by the com- binations sequence. Treatment with each combination lasted 4 weeks. Office blood pressure (BP was assessed at baseline and at the end of the treatment periods, possible side effects were registered.Results. All patients completed the study. Both combination of S-amlodipine+atenolol and fixed combination of racemic amlodipine+atenolol reduced systolic (in average, -15.9 and -12.7 mm Hg, respectively and diastolic (in average, -7.3 and -5.3 mmHg, respectively BP significantly. Heart rate also decreased during therapy (in average, -3 and -4 bt/min, respectively. The differences between combinations BP and heart rate effects were not significant. 8 and 16 adverse events were registered during S-amlodipine+atenolol and racemic amlodipine+atenolol therapies, respectively Conclusion. Combination of S-amlodipine+atenolol, as well as combination of racemic amlodipine+atenolol are effective in the treatment of patients with HT 1-2 degree, however combination with S-amlodipine has less number of adverse events.

  1. Vasorelaxant Effect of a Newly Synthesized Dihydropyridine Ethyl Ester (DHPEE on Rat Thoracic Aorta: Dual Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Hossein Babaei

    2011-06-01

    Full Text Available Introduction: DHPEE is a newly synthesized compound by merging the key structural elements in an angiotensin receptor blocker (Telmisartan with key structural elements in 1,4- dihydropyridine calcium channel blocker (Nifedipine. In this study, we examined dual calcium channel blocking and AT1 antagonist activity for DHPEE. Methods: The functional inhibitory characteristics of DHPEE were studied in vitro in rat thoracic aorta preparations precontracted by phenylephrine (1µM or KCl (80µM or Ang II in normal or calcium-free solutions. Results: Concentration–dependent significant relaxation was observed in aortic rings precontracted with phenylephrine, KCl or Ang II. The tension increment produced by increasing external calcium was also reduced by DHPEE. DHPEE caused a marked decrease in the maximal contractile response of the vasoactive agents and shifted their concentration-response curves to the right. Conclusion: DHPEE possesses dual characteristics and cause vasorelaxation by blocking the L-type calcium channels and blocking Ang II receptors (AT1 in rat aortic smooth muscle.

  2. Prescribing patterns of antihypertensive drugs in geriatric population in tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Renoy Philip

    2016-03-01

    Full Text Available Hypertension is one of the major chronic diseases with high mortality and morbidity in the today’s world. Present study was to assess the prescribing pattern of antihypertensive medications in geriatric population suffering mainly from hypertension with or without co morbidities like Diabetes Mellitus (DM. A prospective observational study was carried out for a period of six months in an in-patient general medicine department. Elderly patients who have been diagnosed with pure hypertension as per JNC 7 guidelines and hypertension with co- morbid condition like diabetes mellitus and patients receiving or prescribed with antihypertensive drugs were included. A total of 150 prescriptions were analyzed. The present study revealed that there were 93 patients with pure Hypertension and 57 patients with co morbid conditions like Diabetes Mellitus (DM. Among antihypertensive drugs in pure hypertensive cases, 53.76% of cases were prescribed with monotherapy, followed by 46.23% by combination therapy. The commonly prescribed antihypertensive monotherapy is calcium channel blockers. The most commonly prescribed combination therapy in severe cases was angiotensin receptor blockers with diuretics. This prescribing pattern of antihypertensives was as per Joint National Committee-7report on hypertension. In case of geriatric patients suffering from hypertension with Type 2 diabetes mellitus, most commonly prescribed antihypertensive as monotherapy was found to be amlodipine and combination therapy was telmisartan + hydrochlorothiazide.

  3. Risk of Cardiovascular Events in Patients With Diabetes Mellitus on β-Blockers

    Science.gov (United States)

    Sugiyama, Takehiro; Shapiro, Martin F.; Noda, Mitsuhiko; Kajio, Hiroshi

    2017-01-01

    Although the use of β-blockers may help in achieving maximum effects of intensive glycemic control because of a decrease in the adverse effects after severe hypoglycemia, they pose a potential risk for the occurrence of severe hypoglycemia. This study aimed to evaluate whether the use of β-blockers is effective in patients with diabetes mellitus and whether its use is associated with the occurrence of severe hypoglycemia. Using the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) data, we performed Cox proportional hazards analyses with a propensity score adjustment. The primary outcome was the first occurrence of a cardiovascular event during the study period, which included nonfatal myocardial infarction, unstable angina, nonfatal stroke, and cardiovascular death. The mean follow-up periods (±SD) were 4.6±1.6 years in patients on β-blockers (n=2527) and 4.7±1.6 years in those not on β-blockers (n=2527). The cardiovascular event rate was significantly higher in patients on β-blockers than in those not on β-blockers (hazard ratio, 1.46; 95% confidence interval, 1.24–1.72; P<0.001). In patients with coronary heart disease or heart failure, the cumulative event rate for cardiovascular events was also significantly higher in those on β-blockers than in those not on β-blockers (hazard ratio, 1.27; 95% confidence interval, 1.02–1.60; P=0.03). The incidence of severe hypoglycemia was significantly higher in patients on β-blockers than in those not on β-blockers (hazard ratio, 1.30; 95% confidence interval, 1.03–1.64; P=0.02). In conclusion, the use of β-blockers in patients with diabetes mellitus was associated with an increased risk for cardiovascular events. PMID:28559400

  4. Simultaneous determination of related substances of telmisartan and hydrochlorothiazide in tablet dosage form by using reversed phase high performance liquid chromatographic method

    Directory of Open Access Journals (Sweden)

    Sutirtho Mukhopadhyay

    2011-01-01

    Full Text Available Objective : Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT 1 receptor that is indicated for the treatment of essential hypertension. Hydrochlorothiazide is a widely prescribed diuretic and it is indicated for the treatment of edema, control of essential hypertension and management of diabetes insipidus. In the current article a new, accurate, sensitive, precise, rapid, reversed phase high performance liquid chromatography (RP-HPLC method was developed for determination of related substances of Telmisartan and Hydrochlorthiazide in tablet dosage form. Materials and Methods : Simultaneous determination of related substances was performed on Kromasil C 18 analytical column (250 × 4.6 mm; 5΅m pertical size column at 40°C employing a gradient elution. Mobile phase consisting of solvent A (solution containing 2.0 g of potassium dihydrogen phosphate anhydrous and 1.04 g of Sodium 1- Hexane sulphonic acid monohydrate per liter of water, adjusted to pH 3.0 with orthophosphoric acid and solvent B (mixture of Acetonitrile: Methanol in the ratio 80:20 v/v was used at a flow rate of 1.0 ml min−1 . UV detection was performed at 270 nm. Results : During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. Conclusions : HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. It may find application for the routine analysis of the related substances of both Telmisartan and Hydrochlorthiazide in this combination tablets.

  5. Simultaneous determination of telmisartan and amlodipine in human plasma by LC–MS/MS and its application in a human pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Vasu Babu Ravi

    2012-10-01

    Full Text Available A rapid and sensitive liquid chromatography–tandem mass spectrometric (LC–MS/MS assay method has been developed and fully validated for the simultaneous quantification of telmisartan and amlodipine in human plasma. Carbamazepine was used as an internal standard. Analytes and the internal standard were extracted from human plasma by solid-phase extraction technique using Waters Oasis® HLB 1 cm3 (30 mg extraction cartridge. The reconstituted samples were chromatographed on a Hypurity advance C18 column (50 mm×4.6 mm, 5 μm using a mixture of acetonitrile–5 mM ammonium acetate buffer (pH-4.0 (50:50, v/v as the mobile phase at a flow rate of 0.8 mL/min. The calibration curve obtained was linear (r≥0.99 over the concentration range of 2.01–400.06 ng/mL for telmisartan and 0.05–10.01 ng/mL for amlodipine. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The proposed method was found to be applicable to clinical studies. Keywords: Telmisartan, Amlodipine, Human plasma, Solid-phase extraction, LC–MS/MS, Pharmacokinetics

  6. Pharmacoepidemiological Beta-blockers consumer research in Ukraine

    Directory of Open Access Journals (Sweden)

    O. Ya. Mishchenko

    2012-12-01

    Full Text Available In this article the results of study of the β-adrenoblockers consumption taking into concideration three parameters - the number of sold packages, money equivalent and the DDDs/1000/d - are given. By the number of sold packages the consumption of β-adrenoblockers is varied slightly during 2008-2010.As for DDDs/1000/d - the part of β-blockers in total consumption of the fi rst line antihypertensive drugs in Ukraine is more than 16% and it is comparable to that in the European countries. For last years the consumption of the most safe selective β1-adrenoblockers has been increasing compared with non-selective drugs, but the consumption of “new” products with strong vasodilating properties (carvedilol and nebivolol is low.

  7. Potassium Channels Blockers from the Venom of Androctonus mauretanicus mauretanicus

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    Marie-France Martin-Eauclaire

    2012-01-01

    Full Text Available K+ channels selectively transport K+ ions across cell membranes and play a key role in regulating the physiology of excitable and nonexcitable cells. Their activation allows the cell to repolarize after action potential firing and reduces excitability, whereas channel inhibition increases excitability. In eukaryotes, the pharmacology and pore topology of several structural classes of K+ channels have been well characterized in the past two decades. This information has come about through the extensive use of scorpion toxins. We have participated in the isolation and in the characterization of several structurally distinct families of scorpion toxin peptides exhibiting different K+ channel blocking functions. In particular, the venom from the Moroccan scorpion Androctonus mauretanicus mauretanicus provided several high-affinity blockers selective for diverse K+ channels  (SKCa,  Kv4.x, and  Kv1.x K+ channel families. In this paper, we summarize our work on these toxin/channel interactions.

  8. Effect of alpha1-blockers on stentless ureteroscopic lithotripsy

    Directory of Open Access Journals (Sweden)

    Jianguo Zhu

    2016-02-01

    Full Text Available ABSTRACT Objective To evaluate the clinical efficiency of alpha1-adrenergic antagonists on stentless ureteroscopic lithotripsy treating uncomplicated lower ureteral stones. Materials and Methods From January 2007 to January 2013, 84 patients who have uncomplicated lower ureteral stones treated by ureteroscopic intracorporeal lithotripsy with the holmium laser were analyzed. The patients were divided into two groups, group A (44 patients received indwelled double-J stents and group B (40 patients were treated by alpha1-adrenergic antagonists without stents. All cases of group B were treated with alpha1 blocker for 1 week. Results The mean operative time of group A was significantly longer than group B. The incidences of hematuria, flank/abdominal pain, frequency/urgency after surgery were statistically different between both groups. The stone-free rate of each group was 100%. Conclusions The effect of alpha1-adrenergic antagonists is more significant than indwelling stent after ureteroscopic lithotripsy in treating uncomplicated lower ureteral stones.

  9. Clinical Outcomes with β-blockers for Myocardial Infarction A Meta-Analysis of Randomized Trials

    DEFF Research Database (Denmark)

    Bangalore, Sripal; Makani, Harikrishna; Radford, Martha

    2014-01-01

    BACKGROUND: Debate exists regarding the efficacy of â-blockers in myocardial infarction and their required duration of usage in contemporary practice. METHODS: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating â-blockers in myocardial infarction enrolling at least 100 ...

  10. Endoscopic therapy and beta-blockers for secondary prevention in adults with cirrhosis and oesophageal varices

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Morgan, Marsha Y.

    2017-01-01

    This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the beneficial and harmful effects of endoscopic therapy and beta-blockers used as a combination therapy versus monotherapy with either endoscopic therapy or beta-blockers for secondary prevention ...... in people with cirrhosis and oesophageal varices....

  11. Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Krag, Aleksander

    2012-01-01

    Non-selective beta-blockers are used as a first-line treatment for primary prevention in patients with medium- to high-risk oesophageal varices. The effect of non-selective beta-blockers on mortality is debated and many patients experience adverse events. Trials on banding ligation versus non...

  12. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices

    DEFF Research Database (Denmark)

    Gluud, Lise L; Klingenberg, Sarah; Nikolova, Dimitrinka

    2007-01-01

    To compare banding ligation versus beta-blockers as primary prophylaxis in patients with esophageal varices and no previous bleeding.......To compare banding ligation versus beta-blockers as primary prophylaxis in patients with esophageal varices and no previous bleeding....

  13. LERCANIDIPINE, CALCIUM CHANNEL BLOCKER OF THE THIRD GENERATION: NEW POSSIBILITIES IN THE TREATMENT OF ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2013-01-01

    Full Text Available Classification, modes of action and clinical effects of calcium channel blockers are presented. Advantages of the third generation of dihydropyridine calcium channel blockers are considered. Clinical pharmacology, studies on the efficacy, safety and prevention of hypertensive complications with lercanidipine are detailed.

  14. Tolerability to beta-blocker therapy among heart failure patients in clinical practice.

    Science.gov (United States)

    Butler, Javed; Khadim, Ghazanfar; Belue, Rhonda; Chomsky, Don; Dittus, Robert S; Griffin, Marie; Wilson, John R

    2003-06-01

    Although beta-blockers were well-tolerated by heart failure (HF) patients in clinical trials, tolerability of these drugs in a general population of HF patients is not well-described. We studied a total of 308 encounters with beta-blockers therapy in 268 ambulatory HF patients. Side effects and frequency and predictors of discontinuation of therapy were studied. Independent predictors of discontinuation were assessed. Weight gain (59%), fatigue (56%), dizziness (41%), and dyspnea (29%) were the most common side effects. Fifty-one patients (19%) were discontinued on therapy with any 1 particular beta-blocker. Fatigue (30%) and hypotension (28%) were the most common reasons for discontinuation. Forty (78%) of these were given a trial with a different beta-blocker. Of these, 22 (55%) attempts with a different beta-blocker were tolerated. Thus the overall absolute discontinuation rate was only 7% for patients who were given a trial with different beta-blockers or 11% for the entire study population. Independent predictors of discontinuation of therapy included advanced symptoms, nonischemic etiology, history of pulmonary disease, and higher diuretic doses. Side effects with beta-blockers in a general population of HF patients are common; however, with changes in medical management, most patients can tolerate them eventually. In case of intolerance to one kind, a trial with a different beta-blocker is indicated.

  15. Discontinuation of β-blockers and the risk of myocardial infarction in the elderly

    NARCIS (Netherlands)

    M. Teichert (Martina); P.A. de Smet (Peter); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); B.H.Ch. Stricker (Bruno)

    2007-01-01

    textabstractBackground: It has been shown that the abrupt cessation of treatment with β-adrenoceptor antagonists (β-blockers) increases the risk of myocardial infarction in patients with hypertension. As β-blockers differ in their pharmacokinetic and pharmacodynamic properties, this risk of

  16. Discontinuation of beta-blockers and the risk of myocardial infarction in the elderly.

    NARCIS (Netherlands)

    Teichert, M.; Smet, P.A.G.M. de; Hofman, A.; Witteman, J.C.; Stricker, B.H.C.

    2007-01-01

    BACKGROUND: It has been shown that the abrupt cessation of treatment with beta-adrenoceptor antagonists (beta-blockers) increases the risk of myocardial infarction in patients with hypertension. As beta-blockers differ in their pharmacokinetic and pharmacodynamic properties, this risk of

  17. Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

    International Nuclear Information System (INIS)

    Choi, Yoon Jung; Lee, Jue Yeon; Lee, Seung Jin; Chung, Chong-Pyoung; Park, Yoon Jeong

    2011-01-01

    Highlights: ► Doxazocin directly up-regulated bone metabolism at a low dose. ► Doxazocin induced osteoblastic stem cell differentiation without affecting cell proliferation. ► This osteogenic stem cell differentiation is mediated by ERK-signal dependent pathway. -- Abstract: Recent researches have indicated a role for antihypertensive drugs including alpha- or beta-blockers in the prevention of bone loss. Some epidemiological studies reported the protective effects of those agents on fracture risk. However, there is limited information on the association with those agents especially at the mechanism of action. In the present study, we investigated the effects of doxazosin, an alpha-blocker that is clinically used for the treatment of benign prostatic hyperplasia (BPH) along with antihypertensive medication, on the osteogenic stem cell differentiation. We found that doxazosin increased osteogenic differentiation of human mesenchymal stem cells, detected by Alizarin red S staining and calcein. Doxazosin not only induced expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin, it also resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK1/2), a MAP kinase involved in osteoblastic differentiation. Treatment with U0126, a MAP kinase inhibitor, significantly blocked doxazosin-induced osteoblastic differentiation. Unrelated to activation of osteogenic differentiation by doxazosin, we found that there were no significant changes in adipogenic differentiation or in the expression of adipose-specific genes, including peroxisome proliferator-activated receptor γ, aP2, or LPL. In this report, we suggest that doxazosin has the ability to increase osteogenic cell differentiation via ERK1/2 activation in osteogenic differentiation of adult stem cells, which supports the protective effects of antihypertensive drug on fracture risk and according to our data doxazosin might be useful for application in the field of bone

  18. Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Jung [Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749 (Korea, Republic of); Lee, Jue Yeon [Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749 (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Lee, Seung Jin [Department of Industrial Pharmacy, College of Pharmacy, Ewha Womans University, Seoul (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Chung, Chong-Pyoung [Department of Periodontology, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Park, Yoon Jeong, E-mail: parkyj@snu.ac.kr [Craniomaxillofacial Reconstructive Sciences Major, College of Dentistry, Seoul National University, Seoul 110-749 (Korea, Republic of); Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Doxazocin directly up-regulated bone metabolism at a low dose. Black-Right-Pointing-Pointer Doxazocin induced osteoblastic stem cell differentiation without affecting cell proliferation. Black-Right-Pointing-Pointer This osteogenic stem cell differentiation is mediated by ERK-signal dependent pathway. -- Abstract: Recent researches have indicated a role for antihypertensive drugs including alpha- or beta-blockers in the prevention of bone loss. Some epidemiological studies reported the protective effects of those agents on fracture risk. However, there is limited information on the association with those agents especially at the mechanism of action. In the present study, we investigated the effects of doxazosin, an alpha-blocker that is clinically used for the treatment of benign prostatic hyperplasia (BPH) along with antihypertensive medication, on the osteogenic stem cell differentiation. We found that doxazosin increased osteogenic differentiation of human mesenchymal stem cells, detected by Alizarin red S staining and calcein. Doxazosin not only induced expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin, it also resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK1/2), a MAP kinase involved in osteoblastic differentiation. Treatment with U0126, a MAP kinase inhibitor, significantly blocked doxazosin-induced osteoblastic differentiation. Unrelated to activation of osteogenic differentiation by doxazosin, we found that there were no significant changes in adipogenic differentiation or in the expression of adipose-specific genes, including peroxisome proliferator-activated receptor {gamma}, aP2, or LPL. In this report, we suggest that doxazosin has the ability to increase osteogenic cell differentiation via ERK1/2 activation in osteogenic differentiation of adult stem cells, which supports the protective effects of antihypertensive drug on fracture risk and

  19. Beta-Blockers for Exams Identify Students at High Risk of Psychiatric Morbidity

    DEFF Research Database (Denmark)

    Butt, Jawad H; Dalsgaard, Søren; Torp-Pedersen, Christian

    2017-01-01

    reasons were excluded. We matched these students on age, sex, and time of year to healthy and study active controls with no use of beta-blockers. Risk of incident use of antidepressants, incident use of other psychotropic medications, and suicide attempts was examined by cumulative incidence curves...... follow-up, 2225 (18.3%) beta-blocker users and 1400 (11.5%) nonbeta-blocker users were prescribed an antidepressant (p psychotropic drug (p ...-blocker users attempted suicide (p = 0.03). Exam-related beta-blocker use was associated with an increased risk of antidepressant use (adjusted HRs, 1.68 [95% confidence intervals (CIs), 1.57-1.79], p psychotropic medication use (HR, 1.93 [95% CI, 1.76-2.12] p 

  20. Beta-blockers and depression in elderly hypertension patients in primary care

    DEFF Research Database (Denmark)

    Ringoir, Lianne; Pedersen, Susanne S.; Widdershoven, Jos W M G

    2014-01-01

    myocardial infarction. The aim of this study was to determine the relation between lipophilic beta-blocker use and depression in elderly primary care patients with hypertension. METHODS: This was a cross-sectional study in primary care practices located in the South of The Netherlands. Primary care......BACKGROUND AND OBJECTIVES: Previous findings regarding a possible association between beta-blocker use and depression are mixed. To our knowledge there have been no studies investigating the association of beta-blockers with depression in primary care hypertension patients without previous...... for potential confounders. CONCLUSIONS: Our findings show that primary care hypertension patients who use a lipophilic beta-blocker are more likely to have higher depression scores than those who do not use a lipophilic beta-blocker....

  1. A randomized study comparing three bronchial blockers, Arndt®, Coopdech® and EZ-blocker® and a double-lumen tube for lung isolation : A manikin study

    NARCIS (Netherlands)

    Mungroop, H. E.; Gennep, L.; Morei, N.; Scheeren, T.; Epema, A. H.

    2011-01-01

    Background and Goal of Study: Double-lumen tubes (DLT) and bronchial blockers (BB) are used for lung isolation and one lung ventilation during thoracic surgery. Recently1 a new Y shaped bronchial blocker was developed, the EZ-Blocker, with two distal extensions to be placed in the two main

  2. Beta-blockers for preventing aortic dissection in Marfan syndrome.

    Science.gov (United States)

    Koo, Hyun-Kyoung; Lawrence, Kendra Ak; Musini, Vijaya M

    2017-11-07

    Marfan syndrome is a hereditary disorder affecting the connective tissue and is caused by a mutation of the fibrillin-1 (FBN1) gene. It affects multiple systems of the body, most notably the cardiovascular, ocular, skeletal, dural and pulmonary systems. Aortic root dilatation is the most frequent cardiovascular manifestation and its complications, including aortic regurgitation, dissection and rupture are the main cause of morbidity and mortality. To assess the long-term efficacy and safety of beta-blocker therapy as compared to placebo, no treatment or surveillance only in people with Marfan syndrome. We searched the following databases on 28 June 2017; CENTRAL, MEDLINE, Embase, Science Citation Index Expanded and the Conference Proceeding Citation Index - Science in the Web of Science Core Collection. We also searched the Online Metabolic and Molecular Bases of Inherited Disease (OMMBID), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 June 2017. We did not impose any restriction on language of publication. All randomised controlled trials (RCTs) of at least one year in duration assessing the effects of beta-blocker monotherapy compared with placebo, no treatment or surveillance only, in people of all ages with a confirmed diagnosis of Marfan syndrome were eligible for inclusion. Two review authors independently screened titles and abstracts for inclusion, extracted data and assessed trial quality. Trial authors were contacted to obtain missing data. Dichotomous outcomes will be reported as relative risk and continuous outcomes as mean differences with 95% confidence intervals. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. One open-label, randomised, single-centre trial including 70 participants with Marfan syndrome (aged 12 to 50 years old) met the inclusion criteria. Participants were randomly assigned to

  3. Development and Validation of Stability Indicating HPTLC and HPLC Methods for Simultaneous Determination of Telmisartan and Atorvastatin in Their Formulations

    Directory of Open Access Journals (Sweden)

    Kaliappan Ilango

    2013-01-01

    Full Text Available The present study describes development and subsequent validation of stability indicating HPLC and HPTLC methods for simultaneous estimation of Telmisartan (TLM and Atorvastatin (ATV in their combined formulation. The proposed RP-HPLC method utilizes a Phenomenex Luna C18 column using acetonitrile: 0.025 M ammonium acetate (38 : 52%, v/v as mobile phase (pH 3.8, flow rate of 1.0 mL/min. Quantification was achieved with UV detection at 281 nm over concentration range of 12 to 72 μg/mL for TLM and 3 to 18 μg/mL for ATV respectively. In HPTLC, separations were performed on silica gel 60 F254 using toluene-methanol-ethyl acetate-acetic acid (5 : 1 : 1 : 0.3, v/v as mobile phase. The compact bands of TLM and ATV at 0.37 ± 0.02 and 0.63 ± 0.01 respectively were scanned at 279 nm. Linear regression analysis revealed linearity in the range of 40 to 240 ng/band for TLM and 10 to 60 ng/band for ATV respectively. For both the methods, dosage form was exposed to thermal, photolytic, acid, alkali and oxidative stress. The methods distinctly separated the drugs and degradation products even in actual samples. In conclusion, the proposed HPLC and HPTLC methods were appropriate for routine quantification of TLM and ATV in tablet formulation.

  4. Telmisartan attenuates colon inflammation, oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Hany H Arab

    Full Text Available Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD via its proinflammatory features. Telmisartan (TLM is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o. attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI, colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-α (TNF-α, prostaglandin E2 (PGE2 and myeloperoxidase (MPO activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10. TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-κB p65 and mRNA of cyclo-oxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS proinflammatory genes with concomitant upregulation of PPAR-γ. The alleviation of TLM to colon injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO besides boosting glutathione (GSH, total anti-oxidant capacity (TAC and the activities of superoxide dismutase (SOD and glutathione peroxidase (GPx. With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It also suppressed the elevation of cytochrome c and Bax mRNA besides the upregulation of Bcl-2. Together, these findings highlight evidences for the beneficial effects of TLM in IBD which are mediated through modulation of colonic inflammation, oxidative stress and apoptosis.

  5. Optimization of self-microemulsifying drug delivery system for telmisartan using Box-Behnken design and desirability function.

    Science.gov (United States)

    Cho, Hyuk Jun; Lee, Dong Won; Marasini, Nirmal; Poudel, Bijay Kumar; Kim, Jeong Hwan; Ramasamy, Thiruganesh; Yoo, Bong Kyu; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2013-10-01

    To develop and optimize the novel self-microemulsifying drug delivery system (SMEDDS) formulation for enhanced water solubility and bioavailability of telmisartan (TMS) using the Box-Behnken design (BBD) and desirability function. TMS-SMEDDS formulation consisted of the mixture of oil (Peceol), surfactant (Labrasol), co-surfactant (Transcutol), TMS and triethanolamine. A three-level BBD was applied to explore the main effect, interaction effect and quadratic effect of three independent variables, including the amount of Peceol (X1 ), Labrasol (X2 ) and Transcutol (X3 ). Determined conditions were 20 < X1  < 40, 50 < X2  < 80 and 5 < X3  < 30. The response variables were droplet size (Y1 ), polydispersity index (Y2 ) and dissolution percentage of TMS after 15 min (Y3 ). The optimized conditions were 28.93, 80 and 28.08 (mg) for X1 , X2 and X3 , respectively, and the response variables were predicted to be 159.8 nm, 0.241 and 85.8% for Y1 , Y2 and Y3 , respectively. The actual values from the optimized formulation showed good agreement with predicted values. The optimized TMS-SMEDDS formulation showed faster drug dissolution rate and higher bioavailability than TMS powder. Our results suggest that response surface methodology using BBD and desirability function is a promising approach to understand the effect of SMEDDS variables and to optimize the formulation. © 2013 Royal Pharmaceutical Society.

  6. The effect of formulation additives on in vitro dissolution-absorption profile and in vivo bioavailability of telmisartan from brand and generic formulations.

    Science.gov (United States)

    Borbás, Enikő; Nagy, Zsombor K; Nagy, Brigitta; Balogh, Attila; Farkas, Balázs; Tsinman, Oksana; Tsinman, Konstantin; Sinkó, Bálint

    2018-03-01

    In this study, brand and four generic formulations of telmisartan, an antihypertensive drug, were used in in vitro simultaneous dissolution-absorption, investigating the effect of different formulation additives on dissolution and on absorption through an artificial membrane. The in vitro test was found to be sensitive enough to show even small differences between brand and generic formulations caused by the use of different excipients. By only changing the type of filler from sorbitol to mannitol in the formulation, the flux through the membrane was reduced by approximately 10%. Changing the salt forming agent as well resulted in approximately 20% of flux reduction compared to the brand formulation. This significant difference was clearly shown in the published in vivo results as well. The use of additional lactose monohydrate in the formulation also leads to approximately 10% reduction in flux. The results show that by changing excipients, the dissolution of telmisartan was not altered significantly, but the flux through the membrane was found to be significantly changed. These results pointed out the limitations of traditional USP dissolution tests and emphasized the importance of simultaneously measuring dissolution and absorption, which allows the complex effect of formulation excipients on both processes to be measured. Moreover, the in vivo predictive power of the simultaneous dissolution-absorption test was demonstrated by comparing the in vitro fluxes to in vivo bioequivalence study results. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Use of Β-Blockers and the Risk of Hip/Femur Fracture in the United Kingdom and The Netherlands

    NARCIS (Netherlands)

    Vries, F. de; Souverein, P.C.; Cooper, C.; Leufkens, H.G.M.; Staa, T.P. van

    2007-01-01

    Data from in vivo studies have indicated a role for Β-blockers in the prevention of bone loss. Some epidemiological studies have found protective effects of b-blockers on fracture risk. However, there is limited information on the association with cumulative dose and type of Β-blockers used. We

  8. Pulmonary vasoconstrictor action of KCNQ potassium channel blockers

    Directory of Open Access Journals (Sweden)

    Balan Prabhu

    2006-02-01

    Full Text Available Abstract Background KCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+ currents mediated by KCNQ channels resemble a current underlying the resting K+ conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction. Methods The tension developed by rat and mouse intrapulmonary or mesenteric arteries was measured using small vessel myography. Contractile responses to linopirdine and XE991 were measured in intact and endothelium denuded vessels. Experiments were also carried out under conditions that prevent the contractile effects of nerve released noradrenaline or ATP, or block various Ca2+ influx pathways, in order to investigate the mechanisms underlying contraction. Results Linopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50 of around 1 μM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or α,β-methylene ATP, to block α1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 μM nifedipine or 10 μM levcromakalim. Conclusion The KCNQ channel blockers are potent and powerful constrictors of pulmonary arteries. This action may be selective for the pulmonary circulation as mesenteric arteries showed little response. The

  9. The review of identification and assay methods of β-blockers

    Directory of Open Access Journals (Sweden)

    Ольга Олександрівна Віслоус

    2015-10-01

    Full Text Available Every year the number of β-blockers on the pharmaceutical market is increasing, requiring systematization of their standardization methods.Aim of research. The aim of our research is to study literature data about identification and assay methods of β-blockers with different direction of action – selective (praktolol, metoprolol, atenolol, acebutolol, betaxolol, bevantolol, bisoprolol, celiprolol, esmolol, epanolol, esatenolol, nebivolol, Talinolol, non-selective (alprenolol, Oxprenololum, pindolol, propranolol, timolol, sotalol, nadolol, mepindolol, karteol, tertatolol, bopindolol, bupranolol, penbutolol, kloranolol and combined (labetalol, carvedilol.Methods. The analytical review of literature sources about β-blockers analysis by physical, chemical, and physicochemical methods.Results. After literature sources’ analyzing it was found that physical and physicochemical constants are basically used for β-blockers pharmacopoeial analysis; both physicochemical values and chemical reactions are used in forensic analysis, resulting in the article.It was founded that titration methods, mostly acid-base titration method, are used for β-blockers assay in the analysis of substances. For β-blockers detection in biological fluids and dosage forms, active pharmaceutical ingredients and metabolites mixture separation one should prefer physicochemical methods, such as gas chromatography and liquid chromatography, absorption UV-Visible spectroscopy, fluorometry, etc.Conclusion. The results have shown can be used for the further search of the identification and assay optimal methods of β-blockers both pure and mixed with other active substances and excipients

  10. An Analysis of Forensic Imaging in the Absence of Write-Blockers

    Directory of Open Access Journals (Sweden)

    Gary C Kessler

    2014-09-01

    Full Text Available Best practices in digital forensics demand use of write-blockers when creating forensic copies of digital media and this has been a core of computer forensics training for decades. The practice is so in-grained that images created without a write-blocker are immediate suspect for integrity. This paper describes a research framework to examine what occurs when a forensic image is acquired without benefit of a write-blocker in order to understand the true impact of such an eventuality. The initial tests document the changes made to a hard drive and flash drive when imaged and examined with a Windows-based forensics workstation.

  11. Beta-blocker therapy and cardiac events among patients with newly diagnosed coronary heart disease

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Shilane, David; Go, Alan S

    2014-01-01

    BACKGROUND: The effectiveness of beta-blockers for preventing cardiac events has been questioned for patients who have coronary heart disease (CHD) without a prior myocardial infarction (MI). OBJECTIVES: The purpose of this study was to assess the association of beta-blockers with outcomes among...... patients with new-onset CHD. METHODS: We studied consecutive patients discharged after the first CHD event (acute coronary syndrome or coronary revascularization) between 2000 and 2008 in an integrated healthcare delivery system who did not use beta-blockers in the year before entry. We used time...

  12. Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

    Directory of Open Access Journals (Sweden)

    Fitzgerald PJ

    2012-06-01

    Full Text Available Paul J FitzgeraldThe Zanvyl Krieger Mind/Brain Institute, Solomon H Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USAAbstract: There is growing evidence that the neurotransmitter norepinephrine (NE and its sister molecule epinephrine (EPI (adrenaline affect some types of cancer. Several recent epidemiological studies have shown that chronic use of beta blocking drugs (which antagonize NE/EPI receptors results in lower recurrence, progression, or mortality of breast cancer and malignant melanoma. Preclinical studies have shown that manipulation of the levels or receptors of NE and EPI with drugs affects experimentally induced cancers. Psychological stress may play an etiological role in some cases of cancer (which has been shown epidemiologically, and this could be partly mediated by NE and EPI released by the sympathetic nervous system as part of the body’s “fight or flight” response. A less well-appreciated phenomenon is that the genetic tone of NE/EPI may play a role in cancer. NE and EPI may affect cancer by interacting with molecular pathways already implicated in abnormal cellular replication, such as the P38/MAPK pathway, or via oxidative stress. NE/EPI-based drugs other than beta blockers also may prevent or treat various types of cancer, as may cholinesterase inhibitors that inhibit the sympathetic nervous system, which could be tested epidemiologically.Keywords: clonidine, guanfacine, aspirin, acetylcholine, epinephrine, adrenaline, sympathetic nervous system, parasympathetic nervous system, inflammation

  13. Calcium channel blockers for primary and secondary Raynaud's phenomenon.

    Science.gov (United States)

    Rirash, Fadumo; Tingey, Paul C; Harding, Sarah E; Maxwell, Lara J; Tanjong Ghogomu, Elizabeth; Wells, George A; Tugwell, Peter; Pope, Janet

    2017-12-13

    Raynaud's phenomenon is a vasospastic disease characterized by digital pallor, cyanosis, and extremity pain. Primary Raynaud's phenomenon is not associated with underlying disease, but secondary Raynaud's phenomenon is associated with connective tissue disorders such as systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease. Calcium channel blockers promote vasodilation and are commonly used when drug treatment for Raynaud's phenomenon is required. To assess the benefits and harms of calcium channel blockers (CCBs) versus placebo for treatment of individuals with Raynaud's phenomenon with respect to Raynaud's type (primary vs secondary) and type and dose of CCBs. We searched the Cochrane Central Register of Controlled Trials (May 19, 2017), MEDLINE (1946 to May 19, 2017), Embase (1947 to May 19, 2017), clinicaltrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Portal. We applied no language restrictions. We also searched bibliographies of retrieved articles and contacted key experts for additional and unpublished data. All randomized controlled trials (RCTs) comparing calcium channel blockers versus placebo. Two review authors independently assessed search results and risk of bias and extracted trial data. We used the GRADE approach to assess the quality of evidence. This review contains 38 RCTs (33 cross-over RCTs) with an average duration of 7.4 weeks and 982 participants; however, not all trials reported all outcomes of interest. Nine of the identified trials studied patients with primary Raynaud's phenomenon (N = 365), five studied patients with secondary Raynaud's phenomenon (N = 63), and the rest examined a mixture of patients with primary and secondary Raynaud's phenomenon (N = 554). The most frequently encountered risk of bias types were incomplete outcome data and poor reporting of randomization and allocation methods.When researchers considered both primary and secondary Raynaud

  14. Antimuscarinics and α-blockers or α-blockers monotherapy on lower urinary tract symptoms--a meta-analysis.

    Science.gov (United States)

    Hao, Nan; Tian, Ye; Liu, Wei; Wazir, Romel; Wang, Jianzhong; Liu, Liangren; Wang, Kunjie; Li, Hong

    2014-03-01

    To assess the clinical efficiency and safety of combination pharmacotherapy of antimuscarinics and α-blockers vs α-blockers monotherapy on patients with moderate to severe lower urinary tract symptoms (LUTS). We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the Cochrane Database of Systematic Review, and Web of Science from their inception until June 2013 to identify all eligible studies that compare the 2 pharmacotherapy strategies on LUTS. The Cochrane Collaboration's RevMan 5.2 software was used for data analysis, and the fixed or the random effect model was selected depending on the proportion of heterogeneity. Eighteen eligible randomized controlled trials were included in this systematic review, including 2106 (51.57%) in cotherapy group and 1978 (48.43%) in monotherapy group. Synthetic data showed that there were significant improvements on Storage International Prostate Symptom Score (mean difference [MD] = -1.51; 95% confidence interval [CI] -2.10 to -0.91, P <.00001), quality of life score (MD = -0.53; 95% CI -0.89 to -0.17, P = .004), micturitions per 24 hours (MD = -1.14; 95% CI -1.84 to -0.45, P = .001), and urgency episodes per 24 hours (MD = -0.99; 95% CI -1.46 to -0.51, P <.0001) in the cotherapy group. There were no significant difference regarding maximum flow rate (MD = -0.05; 95% CI -0.27 to 0.17, P = .64), Total International Prostate Symptom Score (TIPSS) (MD = -0.88; 95% CI -1.64 to -0.12, P = .02), and Voiding International Prostate Symptom Score (VIPSS) (MD = 0.40; 95% CI -0.34 to 1.15, P = .29). As to postvoid residual volume, however, a worse condition was showed in the cotherapy group (MD = -6.53; 95% CI 3.06-10.00, P <.0002). Antimuscarinics could and should be added to the drug regimen for patients with LUTS attributed to benign prostatic hyperplasia/bladder outlet obstruction, particularly are dominated by storage symptoms. For patients with increased acute

  15. Data and calculus on isobolographic analysis to determine the antinociceptive interaction between calcium channel blocker and a TRPV1 blocker in acute pain model in mice

    Directory of Open Access Journals (Sweden)

    Juliana F. Silva

    2017-10-01

    Full Text Available Determining antinociceptive interaction between Phα1β toxin (a voltage gated calcium channel blocker and SB366791 (selective TRPV1 antagonist may have both clinical and mechanistic implications for the pain management. This data in brief article is associated to the research paper “Synergistic antinociceptive effect of a calcium channel blocker and a TRPV1 blocker in an acute pain model in mice”. This material supports the isobolographic analysis performed with the above drugs and shows: data of the dose response curves of the agents given as single drug or combination regimens. Mathematics and statistical processing of dose response curves, proportion of drugs dosage to be used in the combination, calculus of theoretical additive DE20 dose as well as experimentally obtained DE20 are provided. It is also presented details of statistical comparison between theoretical and experimentally obtained DE20.

  16. Dutch pediatricians' views on the use of neuromuscular blockers for dying neonates: a qualitative study

    NARCIS (Netherlands)

    ten Cate, K.; van de Vathorst, S.

    2015-01-01

    To assess Dutch pediatricians' views on neuromuscular blockers for dying neonates. Qualitative study involving in-depth interviews with 10 Dutch pediatricians working with severely ill neonates. Data were analyzed using appropriate qualitative research techniques. Participants explained their view

  17. Effects of beta-adrenergic blockers on drug-induced tremors.

    Science.gov (United States)

    Iwata, S; Nomoto, M; Fukuda, T

    1993-03-01

    We studied the effect of various kinds of beta-adrenergic blockers on oxotremorine-, harmaline- and thyrotropin-releasing hormone (TRH)-induced tremors in mice. To investigate what property of beta-blockers plays the main role in suppressing tremor, we employed five beta-blockers (propranolol, atenolol, butoxamine, pindolol, and arotinolol). All drugs suppressed oxotremorine-induced tremors but none reduced harmaline-induced tremors. Even though TRH-induced tremors were decreased significantly only by propranolol and high doses of arotinolol, all drugs had a tendency to reduce the tremor. We concluded that neuropharmacological mechanisms underlying to harmaline-induced tremors were different from those of TRH- and oxotremorine-induced tremors and that features of beta-blockers (beta 1- or beta 2-selectivity, intrinsic sympathomimetic activity, and membrane stabilizing activity) did not primarily contribute to the suppression of tremors.

  18. Effect of glucose infusion on endurance performance after beta-adrenoceptor blocker administration

    NARCIS (Netherlands)

    van Baak, M.A.; Mooij, J.M.

    1994-01-01

    Effect of glucose infusion on endurance performance after beta-adrenoceptor blocker administration. Van Baak MA, Mooij JM. Department of Human Biology, University of Limburg, Maastricht, The Netherlands. To investigate the effect of glucose (Glc) infusion on endurance performance after

  19. A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome.

    NARCIS (Netherlands)

    Doyle, J.J.; Doyle, A.J.; Wilson, N.K.; Habashi, J.P.; Bedja, D.; Whitworth, R.E.; Lindsay, M.E.; Schoenhoff, F.; Myers, L.; Huso, N.; Bachir, S.; Squires, O.; Rusholme, B.; Ehsan, H.; Huso, D.; Thomas, C.J.; Caulfield, M.J.; Eyk, J.E. Van; Judge, D.P.; Dietz, H.C.; Loeys, B.L.; et al.,

    2015-01-01

    Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and

  20. A meta-analysis of the effects of β-adrenergic blockers in chronic heart failure.

    Science.gov (United States)

    Zhang, Xiaojian; Shen, Chengwu; Zhai, Shujun; Liu, Yukun; Yue, Wen-Wei; Han, Li

    2016-10-01

    Adrenergic β-blockers are drugs that bind to, but do not activate β-adrenergic receptors. Instead they block the actions of β-adrenergic agonists and are used for the treatment of various diseases such as cardiac arrhythmias, angina pectoris, myocardial infarction, hypertension, headache, migraines, stress, anxiety, prostate cancer, and heart failure. Several meta-analysis studies have shown that β-blockers improve the heart function and reduce the risks of cardiovascular events, rate of mortality, and sudden death through chronic heart failure (CHF) of patients. The present study identified results from recent meta-analyses of β-adrenergic blockers and their usefulness in CHF. Databases including Medline/Embase/Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were searched for the periods May, 1985 to March, 2011 and June, 2013 to August, 2015, and a number of studies identified. Results of those studies showed that use of β-blockers was associated with decreased sudden cardiac death in patients with heart failure. However, contradictory results have also been reported. The present meta-analysis aimed to determine the efficacy of β-blockers on mortality and morbidity in patients with heart failure. The results showed that mortality was significantly reduced by β-blocker treatment prior to the surgery of heart failure patients. The results from the meta-analysis studies showed that β-blocker treatment in heart failure patients correlated with a significant decrease in long-term mortality, even in patients that meet one or more exclusion criteria of the MERIT-HF study. In summary, the findings of the current meta-analysis revealed beneficial effects different β-blockers have on patients with heart failure or related heart disease.

  1. Effectiveness of tumor necrosis factor α blockers in early axial spondyloarthritis: data from the DESIR cohort.

    Science.gov (United States)

    Moltó, Anna; Paternotte, Simon; Claudepierre, Pascal; Breban, Maxime; Dougados, Maxime

    2014-07-01

    To estimate the frequency of use and effectiveness in daily practice of tumor necrosis factor α (TNFα) blockers in a population with inflammatory back pain suggestive of early axial spondyloarthritis (SpA). The Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR) cohort is a prospective, multicenter, observational cohort of 708 patients with early (<3 years' duration) inflammatory back pain suggestive of axial SpA. The percentage of patients receiving TNFα blockers over the first 2 years of followup was estimated by survival analysis. To evaluate effectiveness, the primary outcome (40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society criteria [ASAS40]) was compared in patients who received TNFα blockers versus control patients who received any other treatment (usual care). Controls were matched to the patients based on a propensity score method. A total of 30.2% (95% confidence interval [95% CI] 26.7-33.7) patients received at least 1 TNFα blocker during the 24 months of followup. The percentage of ASAS40 responders was 31.5% (62 of 197 patients) in the group receiving TNFα blockers versus 13.2% (26 of 197) in the control group (OR 2.99 [95% CI 1.80-4.99], P = 0.0002). This effectiveness was more pronounced in the subgroup of patients with sacroiliitis identified on magnetic resonance imaging, with 46% of ASAS40 responders receiving TNFα blockers versus 15% of ASAS40 responders receiving usual care (OR 4.99 [95% CI 2.17-11.51]). Our study shows that TNFα blockers are frequently used in daily practice to treat patients with early axial SpA. Our findings confirm the effectiveness of TNFα blockers as compared to any other treatment, especially in the subgroup of patients with sacroiliitis on MRI. Copyright © 2014 by the American College of Rheumatology.

  2. A novel hypothesis for the binding mode of HERG channel blockers

    International Nuclear Information System (INIS)

    Choe, Han; Nah, Kwang Hoon; Lee, Soo Nam; Lee, Han Sam; Lee, Hui Sun; Jo, Su Hyun; Leem, Chae Hun; Jang, Yeon Jin

    2006-01-01

    We present a new docking model for HERG channel blockade. Our new model suggests three key interactions such that (1) a protonated nitrogen of the channel blocker forms a hydrogen bond with the carbonyl oxygen of HERG residue T623; (2) an aromatic moiety of the channel blocker makes a π-π interaction with the aromatic ring of HERG residue Y652; and (3) a hydrophobic group of the channel blocker forms a hydrophobic interaction with the benzene ring of HERG residue F656. The previous model assumes two interactions such that (1) a protonated nitrogen of the channel blocker forms a cation-π interaction with the aromatic ring of HERG residue Y652; and (2) a hydrophobic group of the channel blocker forms a hydrophobic interaction with the benzene ring of HERG residue F656. To test these models, we classified 69 known HERG channel blockers into eight binding types based on their plausible binding modes, and further categorized them into two groups based on the number of interactions our model would predict with the HERG channel (two or three). We then compared the pIC 5 value distributions between these two groups. If the old hypothesis is correct, the distributions should not differ between the two groups (i.e., both groups show only two binding interactions). If our novel hypothesis is correct, the distributions should differ between Groups 1 and 2. Consistent with our hypothesis, the two groups differed with regard to pIC 5 , and the group having more predicted interactions with the HERG channel had a higher mean pIC 5 value. Although additional work will be required to further validate our hypothesis, this improved understanding of the HERG channel blocker binding mode may help promote the development of in silico predictions methods for identifying potential HERG channel blockers

  3. Endogenous endophthalmitis in a rheumatoid patient on tumor necrosis factor alpha blocker

    Directory of Open Access Journals (Sweden)

    Agarwal Pankaj

    2007-01-01

    Full Text Available The development of anti-tumor necrosis factor (TNF therapies is a milestone in the therapy of rheumatic diseases. It is of concern whether all potential undesired complications of therapy have been evaluated within clinical trials which have led to treatment approval. Specialists prescribing TNF blockers should be aware of the unusual and severe complications that can occur. We describe a case of endogenous endophthalmitis in a rheumatoid patient on TNF alpha blocker.

  4. Alpha blockers in the management of ureteric lithiasis: A meta-analysis

    OpenAIRE

    Raison, Nicholas Tobias Johannes; Ahmed, Kamran; Brunckhorst, Oliver; Dasgupta, Prokar

    2017-01-01

    INTRODUCTION:Effective medical expulsion for ureteric stones with α-blockers offers numerous advantages over surgical alternatives. However, its effectiveness remains uncertain and with the publication of new trial data, the available evidence requires reappraisal.OBJECTIVE:The aim of this study was to assess the efficacy of α-blockers the management of ureteric lithiasis.METHODS:A systematic review of the literature, with predefined search criteria, was conducted using PubMed and Embase. All...

  5. β Adrenergic blockers lower renin in patients treated with ACE inhibitors and diuretics

    Science.gov (United States)

    Holmer, S; Hense, H; Danser, A; Mayer, B; Riegger, G; Schunkert, H

    1998-01-01

    Objective—To examine the effect of concomitant intake of β blockers with angiotensin converting enzyme (ACE) inhibitors, diuretics, or both on plasma renin concentrations in a population based sample (MONICA survey, Augsburg, Germany).
Subject and methods—728 individuals were studied, of whom 171 were treated using monotherapy (ACE inhibitor (n = 21), diuretic (n = 10), or β blocker (n = 72)), or combination treatment (ACE inhibitor + diuretic (n = 32), ACE inhibitor + β blocker (n = 7), diuretic + β blocker (n = 22), ACE inhibitor + diuretic + β blocker (n = 7)). The remaining 557 individuals were untreated. Indications for treatment were hypertension (75%), coronary artery disease with (12%) or without (3%) hypertension, or unknown (10%).
Results—Mean (SEM) renin concentrations in individuals treated with an ACE inhibitor (41 (8) mU/l), a diuretic (41 (10) mU/l), or the combination of an ACE inhibitor and a diuretic (54 (10) mU/l) were raised compared with untreated individuals (17 (1) mU/l; p diuretic (22 (4) mU/l), or with both an ACE inhibitor and a diuretic (21 (7) mU/L), were significantly lower compared with renin concentrations in groups not receiving β blocker treatment (p diuretics, or both can be largely prevented by concomitant β blocker treatment.

 Keywords: adrenergic β receptor blocker;  angiotensin converting enzyme inhibitor;  renin;  hypertension PMID:9764058

  6. Oxidation of β-blockers by birnessite: Kinetics, mechanism and effect of metal ions.

    Science.gov (United States)

    Chen, Yong; Lu, Xiye; Liu, Lu; Wan, Dong; Chen, Huabin; Zhou, Danna; Sharma, Virender K

    2018-03-01

    Manganese dioxides are ubiquitous in natural waters, soils, and sediments and play an important role in oxidative transformation of organic pollutants. This work presents the kinetics of the oxidation of selected β-blockers, betaxolol, metoprolol, and atenolol by birnessite (δ-MnO 2 ) as a function of concentration of the β-blocker, dosage of δ-MnO 2 , and solution pH. The values of pseudo-first-order rate constants (k obs ) of β-blockers decreased in the order betaxolol > atenolol > metoprolol, which was positively correlated with their acid dissociation constants (K a ). Effect of series of metal ions (Fe 3+ , Cr 3+ , Al 3+ , Pb 2+ , Cu 2+ , Zn 2+ , Ni 2+ , Cd 2+ , Mg 2+ , and Ca 2+ ) on the degradation of β-blockers by δ-MnO 2 was systematically examined. All of these metal ions inhibited the oxidation reaction under the same constant ionic strength. The inhibition efficiency was positively correlated with the logarithm of stability constant of metal ions in aqueous solution (logK MeOH ). By LC-ESI-MS/MS analyses, the oxidation of β-blockers primarily involved hydroxylation and cleavage of the parent molecules to the short branched chain compounds. An electron transfer mechanism for the oxidation of β-blockers by δ-MnO 2 was proposed. The oxidation was initiated by the electron transfer from the nonbonding electrons on nitrogen (N-electrons) of β-blockers to δ-MnO 2 , followed by transformation of radical intermediates. These findings will help to understand the oxidation processes of β-blockers and predict the effect of metal ions on the removal of pollutants by δ-MnO 2 in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Age-related differences in bitter taste and efficacy of bitter blockers.

    Directory of Open Access Journals (Sweden)

    Julie A Mennella

    Full Text Available Bitter taste is the primary culprit for rejection of pediatric liquid medications. We probed the underlying biology of bitter sensing and the efficacy of two known bitter blockers in children and adults.A racially diverse group of 154 children (3-10 years old and their mothers (N = 118 evaluated the effectiveness of two bitter blockers, sodium gluconate (NaG and monosodium glutamate (MSG, for five food-grade bitter compounds (quinine, denatonium benzoate, caffeine, propylthiouracil (PROP, urea using a forced-choice method of paired comparisons. The trial was registered at clinicaltrials.gov (NCT01407939.The blockers reduced bitterness in 7 of 10 bitter-blocker combinations for adults but only 3 of 10 for children, suggesting that efficacy depends on age and is also specific to each bitter-blocker combination. Only the bitterness of urea was reduced by both blockers in both age groups, whereas the bitterness of PROP was not reduced by either blocker in either age group regardless of TAS2R38 genotype. Children liked the salty taste of the blocker NaG more than did adults, but both groups liked the savory taste of MSG equally.Bitter blocking was less effective in children, and the efficacy of blocking was both age and compound specific. This knowledge will pave the way for evidence-based strategies to help develop better-tasting medicines and highlights the conclusion that adult panelists and genotyping alone may not always be appropriate in evaluating the taste of a drug geared for children.

  8. Nebivolol: a novel beta-blocker with nitric oxide-induced vasodilatation

    Directory of Open Access Journals (Sweden)

    Robert Weiss

    2006-09-01

    Full Text Available Robert WeissAndroscoggin Cardiology Associates, Auburn, ME, USAAbstract: Nebivolol is a novel beta1-blocker with a greater degree of selectivity for beta1- adrenergic receptors than other agents in this class and a nitric oxide (NO-potentiating, vasodilatory effect that is unique among beta-blockers currently available to clinicians (nebivolol is approved in Europe and is currently under review in the US. A NO-potentiating agent such as nebivolol may have an important role in hypertensive populations with reduced endothelial function such as diabetics, African-Americans and those with vascular disease. Nebivolol is a racemic mixture with beta-blocker activity residing in the d-isomer; in contrast, l-nebivolol is far more potent in facilitating NO release. Nebivolol is unique among betablockers in that, at doses <10 mg, it does not inhibit the increase in heart rate normally seen with exercise. The efficacy of nebivolol has been tested successfully in clinical trials against other agents including other beta-blockers, angiotensin-converting enzyme-inhibitors and calcium channel antagonists in patients with hypertension, angina, and congestive heart failure. The tolerability of nebivolol has been shown to be superior to that of atenolol and metoprolol. In controlled clinical trials, nebivolol has a side effect profile that is similar to placebo, in particular as it relates to fatigue and sexual dysfunction. This article will review published clinical data regarding this cardioselective beta-blocker. Keywords: nebivolol, hypertension, beta-blocker

  9. Risk of Cardiovascular Events in Patients With Diabetes Mellitus on β-Blockers.

    Science.gov (United States)

    Tsujimoto, Tetsuro; Sugiyama, Takehiro; Shapiro, Martin F; Noda, Mitsuhiko; Kajio, Hiroshi

    2017-07-01

    Although the use of β-blockers may help in achieving maximum effects of intensive glycemic control because of a decrease in the adverse effects after severe hypoglycemia, they pose a potential risk for the occurrence of severe hypoglycemia. This study aimed to evaluate whether the use of β-blockers is effective in patients with diabetes mellitus and whether its use is associated with the occurrence of severe hypoglycemia. Using the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) data, we performed Cox proportional hazards analyses with a propensity score adjustment. The primary outcome was the first occurrence of a cardiovascular event during the study period, which included nonfatal myocardial infarction, unstable angina, nonfatal stroke, and cardiovascular death. The mean follow-up periods (±SD) were 4.6±1.6 years in patients on β-blockers (n=2527) and 4.7±1.6 years in those not on β-blockers (n=2527). The cardiovascular event rate was significantly higher in patients on β-blockers than in those not on β-blockers (hazard ratio, 1.46; 95% confidence interval, 1.24-1.72; P diabetes mellitus was associated with an increased risk for cardiovascular events. © 2017 The Authors.

  10. Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review

    NARCIS (Netherlands)

    Brewster, Lizzy M.; Seedat, Yackoob K.

    2013-01-01

    Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the

  11. Comparison of the effects of barnidipine+losartan compared with telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in patients with hypertension and type 2 diabetes mellitus.

    Science.gov (United States)

    Derosa, Giuseppe; Querci, Fabrizio; Franzetti, Ivano; Dario Ragonesi, Pietro; D'Angelo, Angela; Maffioli, Pamela

    2015-10-01

    The aim of this study was to evaluate the effects of barnidipine+losartan compared with telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in patients with hypertension and type 2 diabetes mellitus. We enrolled 148 normocholesterolemic patients with mild-to-moderate hypertension and type 2 diabetes mellitus. Patients were treated with barnidipine, 20 mg day(-1), in combination with losartan, 100 mg day(-1), or with telmisartan+hydrochlorothiazide, 80/12.5 mg day(-1), for 6 months. We assessed blood pressure (BP) on a monthly basis; additionally, blood samples were collected to assess, at baseline and after 6 months, the following parameters: fasting plasma glucose; glycated hemoglobin; fasting plasma insulin; HOMA index; and some adipocytokines, such as adiponectin (ADN), resistin, leptin, visfatin and vaspin. Patients were also subjected to an euglycemic hyperinsulinemic clamp to assess the M value and glucose infusion rate to ascertain their insulin sensitivity. One hundred and forty-one patients completed the study. The BP was reduced in both groups, although the reduction was greater with barnidipine+losartan (Phydrochlorothiazide). Barnidipine+losartan increased the M value and glucose infusion rate during the euglycemic hyperinsulinemic clamp (Phydrochlorothiazide). With respect to the levels of adipocytokines, ADN was increased (Phydrochlorothiazide. Visfatin and vaspin were reduced by barnidipine+losartan compared with baseline (Phydrochlorothiazide (P<0.05 for all parameters). In addition to providing a greater BP reduction, barnidipine+losartan improved the insulin sensitivity, as assessed by an euglycemic hyperinsulinemic clamp, and improved some of the adipocytokines related to insulin resistance.

  12. Risk of insomnia attributable to β-blockers in elderly patients with newly diagnosed hypertension.

    Science.gov (United States)

    Chang, Chia-Hsien; Yang, Yea-Huei Kao; Lin, Swu-Jane; Su, Jyun-Jhong; Cheng, Ching-Lan; Lin, Li-Jen

    2013-01-01

    Use of β-blockers may cause insomnia and central nervous system and/or psychological side effects, but data are limited on the relative risks of insomnia among β-blockers. This retrospective cohort study used Taiwan's National Health Insurance claims database from 2003 to 2007, where 4,063 patients aged above 65 years with newly diagnosed hypertension and treated with β-blockers were followed for 1 year. The primary endpoint was a new insomnia event within 30 days of treatment initiation. Adjusted odds ratios of insomnia were obtained by logistic regressions, controlling for baseline risk factors of insomnia. Using propranolol therapy as the reference, the adjusted odds ratio (95% confidence interval) for the insomnia risk was 0.47 (0.35-0.63) for non-propranolol users, 0.31 (0.19-0.50) for bisoprolol, and 0.46 (0.33-0.66) for atenolol. Compared to the patients using non-selective β-blockers, the adjusted odds ratio was 0.48 (0.36-0.34) for those using selective β(1)-blockers. Additionally, the adjusted odds ratio was 0.72 (0.53-0.96) for β-blockers with low lipophilicity when compared to those with high lipophilicity. The use of bisoprolol and atenolol was associated with the lowest risk of insomnia in elderly patients, as compared to propranolol. β-Blockers with high selectivity in β(1)-receptors and/or low lipophilicity were associated with a lower risk of insomnia.

  13. Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention.

    Directory of Open Access Journals (Sweden)

    Madhu Nath

    Full Text Available Examining the Retinal Renin Angiotensin System (RRAS in the ROP neonates and analyzing the possibility of modulating the RRAS to prevent the progression in Oxygen Induced Retinopathy (OIR model.Vitreous of ROP patients (n = 44, median age 5.5 months was quantified for RRAS components, VEGF, HIF-1α and compared with age matched control. The involvement of RRAS in ROP was tested in the rat model of OIR and compared with normoxia. Expressions of RAS components, VEGF and HIF-1α in retina were analyzed using qPCR and retinal structure and function was also analyzed. Effect of Angiotensin Converting Enzyme Inhibitor (ACEI and Angiotensin Receptor Blocker (ARB was evaluated and compared with Bevacizumab which served as a positive control. Drug penetration into retina was confirmed by liquid chromatography coupled ESI-tandem mass spectroscopy (LC-MS/MS.Multifold increase in the expression of RAS components in human vitreous and rat retina showed their involvement in ROP. ERG & fundus studies in OIR revealed the altered function of retina and were successfully prevented by ARB (telmisartan, ACEI (lisinopril and bevacizumab. Retinal analysis revealed the presence of ACEI and ARB in their therapeutic levels.This study for the first time demonstrates the upregulated level of RAS components in human ROP vitreous and further that the pharmacological intervention in RRAS can functionally and structurally preserve retina against the progression of ROP in the OIR model.

  14. Effects of Salt Supplementation on the Albuminuric Response to Telmisartan With or Without Hydrochlorothiazide Therapy in Hypertensive Patients With Type 2 Diabetes Are Modulated by Habitual Dietary Salt Intake

    OpenAIRE

    Ekinci, Elif I.; Thomas, Georgina; Thomas, David; Johnson, Cameron; MacIsaac, Richard J.; Houlihan, Christine A.; Finch, Sue; Panagiotopoulos, Sianna; O'Callaghan, Chris; Jerums, George

    2009-01-01

    OBJECTIVE This prospective randomized double-blind placebo-controlled crossover study examined the effects of sodium chloride (NaCl) supplementation on the antialbuminuric action of telmisartan with or without hydrochlorothiazide (HCT) in hypertensive patients with type 2 diabetes, increased albumin excretion rate (AER), and habitual low dietary salt intake (LDS; 200 mmol sodium/24 h on two of three consecutive occasions). RESEARCH DESIGN AND METHODS Following a washout period, subjects (n = ...

  15. Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension

    Directory of Open Access Journals (Sweden)

    Sha-Sha Huang

    2016-10-01

    Full Text Available Introduction: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes derived from Xinjiang Kazakh patients with hypertension. Methods: CD4+ T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4+ T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively. Results: The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment. Conclusions: Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4+ T lymphocytes.

  16. Next Step in Chronic Kidney Disease Therapy

    Directory of Open Access Journals (Sweden)

    D.D. Ivanov

    2016-04-01

    Full Text Available Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers are the basis of renoprotection therapy in chronic kidney disease. Parallel to decrease of glomerular filtration rate, there is an increase in the activity of the sympathetic nervous system, and the number of functio­ning nephrons reduces, which requires a change of treatment regimen. Reducing the risk of cardiovascular events on the background of increased hypertension probably dictates the need for a priority administration of sympatholytics, calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers withdrawal. ARAMONEL formula: ARAMONEL — AR(BA(CEIMO(xonidineNE(bivololL(ercandipine is changed to MNELD — M(oxonidineNE(bivololL(ercandipineD(iuretic that is used by us in recent years. Combined use of torsemide and xipamide is allowed. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers withdrawal requires evidence, which may be obtained in STOP-ACEi trial.

  17. The putative P-gp inhibitor telmisartan does not affect the transcellular permeability and cellular uptake of the calcium channel antagonist verapamil in the P-glycoprotein expressing cell line MDCK II MDR1

    DEFF Research Database (Denmark)

    Saaby, Lasse; Tfelt-Hansen, Peer; Brodin, Birger

    2015-01-01

    of verapamil. Fluxes of radiolabelled verapamil across MDCK II MDR1 monolayers were measured in the absence and presence of the putative P-gp inhibitor telmisartan (a clinically approved drug compound). Verapamil displayed a vectorial basolateral-to-apical transepithelial efflux across the MDCK II MDR1...... monolayers with a permeability of 5.7 × 10−5 cm sec−1 compared to an apical to basolateral permeability of 1.3 × 10−5 cm sec-1. The efflux could be inhibited with the P-gp inhibitor zosuquidar. Zosuquidar (0.4 μmol/L) reduced the efflux ratio (PB-A/PA-B) for verapamil 4.6–1.6. The presence of telmisartan......, however, only caused a slight reduction in P-gp-mediated verapamil transport to an efflux ratio of 3.4. Overall, the results of the present in vitro approach indicate, that clinical use of telmisartan as a P-gp inhibitor may not be an effective strategy for increasing brain uptake of verapamil by co...

  18. Optimal use of β-blockers in high-risk hypertension: A guide to dosing equivalence

    Directory of Open Access Journals (Sweden)

    Janet B McGill

    2010-05-01

    Full Text Available Janet B McGillDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri, USAAbstract: Hypertension is the number one diagnosis made by primary care physicians, placing them in a unique position to prescribe the antihypertensive agent best suited to the individual patient. In individuals with diabetes mellitus, blood pressure (BP levels > 130/80 mmHg confer an even higher risk for cardiovascular and renal disease, and these patients will benefit from aggressive antihypertensive treatment using a combination of agents. β‑blockers are playing an increasingly important role in the management of hypertension in high-risk patients. β‑blockers are a heterogeneous class of agents, and this review presents the differences between β‑blockers and provides evidence-based protocols to assist in understanding dose equivalence in the selection of an optimal regimen in patients with complex needs. The clinical benefits provided by β‑blockers are only effective if patients adhere to medication treatment long term. β‑blockers with proven efficacy, once-daily dosing, and lower side effect profiles may become instrumental in the treatment of hypertensive diabetic and nondiabetic patients.Keywords: antihypertensive, blood pressure, atenolol, carvedilol, labetalol, metoprolol, nebivolol

  19. Differential effects of 3 beta blockers on lipid peroxidation in hyperthyroid muscle.

    Science.gov (United States)

    Asayama, K; Hayashibe, H; Dobashi, K; Kato, K

    1990-08-01

    To determine whether beta blockade protects against the acceleration of lipid peroxidation in hyperthyroid rat soleus (slow-oxidative) muscle, in vivo chronic (3 weeks) effects of 3 beta blockers with different ancillary properties on mitochondrial oxidative enzymes, antioxidant enzymes, and thiobarbituric acid-reactive substances were investigated. The rats were rendered hyperthyroid by the administration of thyroxine and treated simultaneously with either carteolol (a nonselective blocker with partial agonist activity; 30 mg/kg/day), atenolol (a beta 1-selective blocker; 50 mg/kg/day), or arotinolol (a nonselective blocker with weak alpha-blocking action; 50 mg/kg/day) over a 3 week period. Hyperthyroidism induced tachycardia, an increase in the mitochondrial oxidative enzymes, manganese (mitochondrial) superoxide dismutase and thiobarbituric acid-reactive substances, and a decrease in the other antioxidant enzymes. The tachycardia was alleviated completely by either atenolol or arotinolol, but partially by carteolol. Arotinolol, but neither carteolol nor atenolol, inhibited the increase in oxidative enzymes and thiobarbituric acid-reactive substances. The levels of antioxidant enzymes were minimally affected by the beta-blocker treatment. Beta 2-, and possibly alpha- as well, but not beta 1-, blockade suppressed mitochondrial hypermetabolism and protected against peroxidative injury in the hyperthyroid soleus muscle. Partial agonist activity was not beneficial.

  20. Use of Calcium Channel Blockers and Risk of Breast Cancer: A Population-based Cohort Study.

    Science.gov (United States)

    Azoulay, Laurent; Soldera, Sara; Yin, Hui; Bouganim, Nathaniel

    2016-07-01

    Several observational studies have associated use of calcium channel blockers with an increased risk of breast cancer, but this association remains controversial. The objective of this study was to determine whether these drugs are associated with an increased risk of breast cancer overall, and to assess whether this risk varies with cumulative duration of use. We identified a cohort of 273,152 women newly treated with antihypertensive drugs between 1 January 1995 and 31 December 2009, followed until 31 December 2010, using the UK Clinical Practice Research Datalink. We treated calcium channel blocker use as a time-varying variable, and lagged exposure by 1 year for latency considerations and to minimize reverse causality. We used time-dependent Cox proportional hazards models to estimate adjusted hazard ratios with 95% confidence intervals of incident breast cancer associated with use of calcium channel blockers overall and by cumulative duration of use (cancer (incidence rate: 2.9 per 1,000 per year). Compared with use of other antihypertensive drugs, use of calcium channel blockers was not associated with increased risk of breast cancer overall (hazard ratio: 0.97, 95% confidence interval: 0.91, 1.03). Similarly, there was no evidence of a duration-response relationship in terms of cumulative duration of use (P trend = 0.26). The results of this large population-based study indicate that long-term use of calcium channel blockers is not associated with an increased risk of breast cancer.

  1. Receptor blockers - general aspects with respect to their use in domestic animal reproduction.

    Science.gov (United States)

    Hoffmann, B; Schuler, G

    2000-07-02

    Receptor blockers compete with the respective agonist for binding to a given receptor without inducing complete signal transduction. In recent years, major interest has focused on sex-steroid hormone receptor blockers (antagonists). Indications have been obtained that inadequate changes in receptor conformation and subsequent failure of transcriptional activation are major events preventing hormonal activity. However, various subtypes and variants of receptors and receptor mutations have also been identified. Expression of antihormonal effects may vary depending on the type of receptor the blocker is bound to. Hence, receptor blockers may also have an inherent agonistic activity. Aglepristone is the first antiprogestin registered for veterinary use with the indication "interruption or prevention of pregnancy"; similarly, these types of compounds were successfully used for induction of parturition in the dog and cat and for conservative treatment of pyometra in the dog. Moreover, application of antiprogestins has clearly demonstrated the role of progesterone as a major factor controlling overt pseudopregnancy in dogs. With respect to farm animals, parturition was induced in cows without an increased incidence of retained fetal membranes. Other than antiprogestins, antioestrogens and antiandrogens are still in a more experimental phase. In particular for use in humans, high-affinity blockers binding to the oxytocin/vasopressin receptor are in development; they exert distinct tocolytic activities. Also, the release of GnRH can be inhibited by respective antagonists; however, their use in reproduction is still hampered by the high dose requirement and the side effects observed.

  2. [Can preoperative administration of H2 blocker reduce the incidence of postoperative nausea and vomiting (PONV)?].

    Science.gov (United States)

    Nozaki, Chisato; Morioka, Nobutada; Kinoshita, Maho; Takada, Mikiko; Ozaki, Makoto

    2007-10-01

    PONV is a complication that reduces a patient's quality of life (QOL). Recently, it was reported that PONV is reduced by preoperative administration of histamine receptor (H1 and H2) inhibitor. In the present study, based on the hypothesis that PONV might be reduced by preoperative administration of H2 blocker, we examined the effect of preoperative administration of H2 blocker only on the incidence of PONV. Eighty seven patients having regular operations were randomly assigned into two groups; the control (C), and the H2 blocker (F) groups. In the operating room, 20 min after intravenous injection of famotidine 20 mg as H2 blocker, anesthesia was maintened by sevofluorane, oxygen, nitrous oxide, and fentanyl following the induction by fentanyl, propofol, and vecuronium. The frequency and extent of vomiting were observed and the patients were interviewed at postoperative hours 0-6 and 6-12. The incidences between the two groups were examined using the chi-squared test. No significant difference in the appearance of PONV was found between the F group and the C group. In women in the F group, the incidence of vomiting was lower. Preoperative administration of H2 blocker tends to reduce PONV in women.

  3. Outcomes in adolescents with postural orthostatic tachycardia syndrome treated with midodrine and beta-blockers.

    Science.gov (United States)

    Lai, Cindy C; Fischer, Philip R; Brands, Chad K; Fisher, Jennifer L; Porter, Co-Burn J; Driscoll, Sherilyn W; Graner, Kevin K

    2009-02-01

    Postural orthostatic tachycardia syndrome (POTS) is associated with debilitating fatigue, dizziness, and discomfort in previously healthy adolescents. The effects of medical therapy have not been well studied in this patient population. This study assessed the relative efficacy and impact of drug therapy on the functioning and quality of life in adolescents with POTS. A retrospective, single center, chart review analysis with a follow-up written survey was conducted on a group of 121 adolescents who had undergone autonomic reflex screening at the Mayo Clinic from 2002 to 2005 as part of an evaluation for possible POTS. Of 121 surveys sent, 47 adolescents returned a completed survey. In this cohort of patients, the two most commonly prescribed drug therapies were midodrine (n = 13) and beta-blockers (n = 14). Patients in the midodrine group were comparable to patients in the beta-blocker group in gender, age, pretreatment postural heart rate changes, and months from initial evaluation to survey completion. More patients treated with a beta-blocker reported improvement after visiting Mayo Clinic (100% vs 62%, P = 0.016) and more attributed their progress to medication (63.6% vs 36.4%, P = 0.011) than did those treated with midodrine. Treatment with both midodrine and beta-blockers was associated with overall improvement in POTS patients' general health; however, adolescents taking beta-blockers were more likely than those taking midodrine to credit the role of medications in their improvement.

  4. Perfil do tratamento da insuficiência cardíaca na era dos betabloqueadores Heart failure treatment profile at the beta blockers era

    Directory of Open Access Journals (Sweden)

    Christiano Pereira Silva

    2007-04-01

    perspective of survival in these patients, as well as allowing the improvement of the quality of life. The aim of this study was to evaluate the reality of the treatment employed and its impact on the disease in patients followed at a specialized heart failure (HF outpatient clinic. METHODS: A sample of 96 patients followed at the HF and Transplant Outpatient Clinic of Heart Institute of the University of São Paulo School of Medicine (InCor -HCFMUSP were evaluated. The data were collected during the ambulatory consultation from the medical files and through physical examination. Patients were randomly selected for the study. RESULTS: Most of the patients were Functional Class II (42.3% and evolution stage C (94.9%. The medical prescription given to the patients was quite similar to the one recommended by the directives. Approximately 95% of them received RAAS inhibitors (ACE inhibitor - enalapril and captopril - or angiotensin receptor antagonist - losartan, whereas 85% of the patients additionally received beta blockers (carvedilol. The mean dose prescribed was also similar to the one used in large studies and reached more than 60% of the maximum dose for each medication. The hemodynamic data show that patients were stable, despite the intensity of the dysfunction and ventricular remodeling observed in these patients. CONCLUSION: Patients with HF followed by a specialized medical team receive a medical prescription that is closer to the recommended one. These patients, despite the marked characteristics of disease severity, achieve hemodynamic and clinical stability with an adequate therapeutic optimization.

  5. SARTANS OF THE SECOND GENERATION: THERAPEUTIC POTENTIAL EXTENSION

    Directory of Open Access Journals (Sweden)

    S. V. Nedogoda

    2011-01-01

    Full Text Available Peculiarities of the treatment with angiotensin II receptor blocker telmisartan are analyzed taking into account its clinical and pharmacological characteristics. Special attention is paid to the telmisartan benefits in comparison with other sartans. Key details of telmisartan interaction with peroxisome proliferator-activated receptors (PPAR are discussed. Mode of this interaction distinguishes pharmacodynamic effects of different medicines. On the basis of presented data author concludes that antihypertensive therapy with telmisartan provides significant benefits.

  6. In Silico Predictions of hERG Channel Blockers in Drug Discovery

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Sørensen, Flemming Steen

    2011-01-01

    on current methods to predict hERG blockers and the need of consistent data to improve the quality and performance of the in silico models. Finally, integration of network-based analysis on drugs inducing potentially long-QT syndrome and arrhythmia will be discussed as a new perspective for a better......The risk for cardiotoxic side effects represents a major problem in clinical studies of drug candidates and regulatory agencies have explicitly recommended that all new drug candidates should be tested for blockage of the human Ether-a-go-go Related-Gene (hERG) potassium channel. Indeed, several...... drugs with different therapeutic indications and recognized as hERG blockers were recently withdrawn due to the risk of QT prolongation, arrhythmia and Torsade de Pointes.In silico techniques can provide a priori knowledge of hERG blockers, thus reducing the costs associated with screening assays...

  7. USE OF BETA-BLOCKERS IN THE PERIOPERATIVE PERIOD: HOW STRONG ARE THE EVIDENCES?

    Directory of Open Access Journals (Sweden)

    V. V. Samoylenko

    2015-09-01

    Full Text Available Optimization of the pharmacotherapy in preoperative period is the cornerstone of the concept of risk modification of cardiovascular complications in the perioperative period. Therefore, special attention has recently been focused on the use of beta-blockers in the postoperative period. Nowadays convincing evidence base for the use of this class of drugs in the perioperative period that was the basis for the development of clinical guidelines is accumulated. Moreover, results of large randomized trials of beta-blockers are controversial. This has resulted in significant differences in the classes of recommendations and levels of evidence.Analysis of the results of basic researches and the provisions of recommendations of the international and national professional medical societies on the use of beta-blockers in patients with cardiovascular disease to reduce the risk of cardiac complications in the perioperative period for planned extracardiac surgical procedures is presented.

  8. Heart rate and use of beta-blockers in stable outpatients with coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Ph Gabriel Steg

    Full Text Available BACKGROUND: Heart rate (HR is an emerging risk factor in coronary artery disease (CAD. However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR. METHODS AND FINDINGS: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of >50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. Most of the 33,177 patients included in this analysis were men (77.5%. Mean (SD age was 64.2 (10.5 years, HR by pulse was 68.3 (10.6 bpm, and by electrocardiogram was 67.2 (11.4 bpm. Overall, 44.0% had HR ≥ 70 bpm. Beta-blockers were used in 75.1% of patients and another 14.4% had intolerance or contraindications to beta-blocker therapy. Among 24,910 patients on beta-blockers, 41.1% had HR ≥ 70 bpm. HR ≥ 70 bpm was independently associated with higher prevalence and severity of angina, more frequent evidence of myocardial ischemia, and lack of use of HR-lowering agents. CONCLUSIONS: Despite a high rate of use of beta-blockers, stable CAD patients often have resting HR ≥ 70 bpm, which was associated with an overall worse health status, more frequent angina and ischemia. Further HR lowering is possible in many patients with CAD. Whether it will improve symptoms and outcomes is being tested.

  9. Why do hypertensive patients of African ancestry respond better to calcium blockers and diuretics than to ACE inhibitors and β-adrenergic blockers? A systematic review

    Science.gov (United States)

    2013-01-01

    Background Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. Methods Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. Results We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. Conclusion Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs. PMID:23721258

  10. Declining risk of sudden death in heart failure

    DEFF Research Database (Denmark)

    Shen, Li; Jhund, Pardeep S.; Petrie, Mark C.

    2017-01-01

    BACKGROUND The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorti...

  11. What role does African ancestry play in how hypertensive patients respond to certain antihypertensive drug therapy?

    NARCIS (Netherlands)

    Seedat, Yackoob K.; Brewster, Lizzy M.

    2014-01-01

    This article is a summary of the response of the four commonly used antihypertensive agents in African ancestry patients. They are thiazide like diuretics or indapamide, calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers, and β-adrenergic

  12. Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the life study

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Kontula, Kimmo; Benn, Marianne

    2010-01-01

    OBJECTIVE: This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the beta-blocker atenolol for 4.8 years tested w...

  13. Self-reported use of evidence-based medicine and smoking ...

    African Journals Online (AJOL)

    Background. Good evidence exists to support the use of secondary prevention medications (aspirin, statins, beta-blockers and angiotensinconverting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs)) and smoking cessation in patients after acute coronary syndromes (ACSs). Little is currently known about ...

  14. Transport of beta-blockers and calcium antagonists by diffusion in cat myocardium

    DEFF Research Database (Denmark)

    Haunsø, Stig; Sejrsen, Per; Svendsen, Jesper Hastrup

    1991-01-01

    Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion. In anesthet......Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion...... collateral blood flow is achieved....

  15. DOGMAS AND UPDATES ON THE USE OF BETA-BLOCKERS IN SECONDARY PREVENTION. FIRST PART.

    Directory of Open Access Journals (Sweden)

    Alberto Morales Salinas

    2011-08-01

    Full Text Available There is consensus on clinical guidelines that beta-blockers (BB provide unquestionable benefits in several environments of secondary prevention, such as heart failure and myocardial infarction. However, in everyday practice they are underused in contexts where they are not contraindicated. Such is the case of heart failure with ejection fraction. This article presents an analysis on the available evidence of beta blockers’ effectiveness in heart failure with ejection fraction. It is concluded that overwhelming evidence favours the use of beta-blockers in chronic heart failure with ejection fraction, whereas in episodes of acute decompensated heart failure, their suspension should be avoided whenever it is possible.

  16. Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

    DEFF Research Database (Denmark)

    Thiele, Maja; Wiest, Reiner; Gluud, Lise Lotte

    2013-01-01

    carcinoma via a reduction of the inflammatory load from the gut to the liver and inhibition of angiogenesis. Due to their effect on the portal pressure, non-selective beta-blockers are used for prevention of esophageal variceal bleeding. Recently, non-hemodynamic effects of beta-blockers have received......-up. Observational studies carry a high risk of bias. The meta-analytic approach may be used if the incidence and mortality of hepatocellular carcinoma can be extracted from trials on variceal bleeding and if the combined sample size and follow up is sufficient....

  17. The value of β-blockers administration during recovery phase of dobutamine stress echocardiography: a review.

    Science.gov (United States)

    Nguyen, James; Juneman, Elizabeth; Movahed, Mohammad Reza

    2013-07-01

    Dobutamine stress echocardiography (DSE) is a successful technique for detection of ischemia in patients with suspected coronary artery disease (CAD). There are some data that administration of β-blocker after peak infusion of dobutamine can improve sensitivity. The goal of this manuscript is to review the current literature in regard to the mechanism and accuracy of post-dobutamine β-blocker administration for ischemia detection. In this review, we present 2 case reports followed by detailed review of the literature. © 2013. This article is a U.S. Government work and is in the public domain in the USA.

  18. Alpha 1-blockers vs 5 alpha-reductase inhibitors in benign prostatic hyperplasia. A comparative review

    DEFF Research Database (Denmark)

    Andersen, J T

    1995-01-01

    During recent years, pharmacological treatment of symptomatic benign prostatic hyperplasia (BPH) has become the primary treatment choice for an increasing number of patients. The 2 principal drug classes employed are alpha 1-blockers and 5 alpha-reductase inhibitors. Current information from...... of patients who will respond well to alpha 1-blockers have yet to be identified, and data concerning the long term effects of these drugs are not yet available. 5 alpha-Reductase inhibitors have a slow onset of effect, but treatment leads to improvement in symptoms, reduction of the size of the prostate gland...... or unwilling to undergo surgical resection of the prostate will benefit from such therapy....

  19. Beta-blocker use and fall risk in older individuals: Original results from two studies with meta-analysis

    NARCIS (Netherlands)

    Ham, Annelies C.; van Dijk, Suzanne C.; Swart, Karin M. A.; Enneman, Anke W.; van der Zwaluw, Nikita L.; Brouwer-Brolsma, Elske M.; van Schoor, Natasja M.; Carola Zillikens, M.; Lips, Paul; de Groot, Lisette C. P. G. M.; Hofman, Albert; Witkamp, Renger F.; Uitterlinden, André G.; Stricker, Bruno H.; van der Velde, Nathalie

    2017-01-01

    Aims To investigate the association between use of -blockers and beta-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism - and fall risk. Methods Data from two prospective studies were used, including community-dwelling

  20. Synthesis and Effects of Novel Dihydropyridines as Dual Calcium Channel Blocker and Angiotensin Antagonist on Isolated Rat Aorta

    Directory of Open Access Journals (Sweden)

    Farzin Hadizadeh

    2010-01-01

    Full Text Available Four novel losartan analogues 5a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of 5a and 5b on angiotensin receptors (AT1 and L-type calcium channels were investigated on isolated rat aorta. Materials and MethodsAortic rings were pre-contracted with 1 µM Angiotensin II or 80 mM KCl and relaxant effects of losartan, nifedipine, 5a and 5b were evaluated by cumulative addition of these drugs to the bath solution.ResultsThe results showed that compounds 5a and 5b have both L-type calcium channel and AT1 receptor blocking activity. Their effects on AT1 receptors are 1000 and 100,000 times more than losartan respectively. The activity of compound 5b on L-type calcium channel is significantly less than nifedipine but compound 5a has comparable effect with nifedipine. ConclusionFinally we concluded that these two new Compounds can be potential candidates to be used as effective antihypertensive agents.

  1. The pharmaco-economics of peri-operative beta-blocker and statin ...

    African Journals Online (AJOL)

    at 2 years.16.17 Because all drugs have potential adverse side- effects, we have attempted to determine the overall incidences of adverse cardiovascular outcomes potentially attributable to beta-blocker administration, including hypotension and bradycardia needing treatment, congestive heart failure, bronchospasm and ...

  2. β-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery

    DEFF Research Database (Denmark)

    Jørgensen, Mads E; Hlatky, Mark A; Køber, Lars Valeur

    2015-01-01

     (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). RESULTS: The baseline characteristics of the 14,644 patients who received β-blockers (65% female, mean [SD...

  3. Bed blockers: A study on the elderly patients in a teaching hospital in India

    Directory of Open Access Journals (Sweden)

    Praveen Kumar N

    2010-07-01

    Full Text Available A cross-sectional study of in-patients over the age of 60 years was conducted at district McGann Hospital, Shimoga on patients who were classified as bed blockers. Level of dependency and cognitive function of these patients were assessed using Barthel scale and Abbreviated mental test (AMT respectively. Median age of the study population was 67 years; majority of them were men. Most of them were admitted in the medical ward and the median time to be labeled as bed blocker was 32 days. These bed blockers were a weak group of patients with an average 3.1 pathology per case. Majority of them suffered from neurological disorders and cardiovascular disease. High level of dependence was noted with a mean Barthel score of 29.68 (Range 0 -100. Low levels of cognitive function was also noted among these patients with a mean AMT of 4.76 (Range 0 -10.These findings demonstrate that the bed blockers in McGann hospital suffer not only from genuine health problems but also have a high dependency level in activities of daily living which hamper their discharge to the community. Community based rehabilitation using an intersectoral approach may help at least the less dependent to return home.

  4. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Kristensen, Karl Emil; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar

    2015-01-01

    OBJECTIVE: The renin-angiotensin system is thought to play a pivotal role in the pathogenesis of abdominal aortic aneurysms (AAAs). However, effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on human AAAs remain unclear. We therefore ex...

  5. Discontinuation of alpha-blocker therapy in male lower urinary tract symptoms: A systematic review

    NARCIS (Netherlands)

    Hordijk, I.; Korteschiel, L.; Steffens, M.; Lisman-van Leeuwen, Y.; Blanker, M.

    2016-01-01

    Hypothesis / aims of study Alpha-blockers are the cornerstone for the medical treatment of male LUTS [1]. Despite the positive recommendation in all relevant guidelines, the efficacy of these drugs has been debated [2]. The Dutch general practitioners guideline Male LUTS recommends the

  6. Topical ophthalmic beta blockers may cause release of histamine through cytotoxic effects of inflammatory cells

    NARCIS (Netherlands)

    Beek, van L.M.; Mulder, M.; Haeringen, van N.J.; Kijlstra, A.

    2000-01-01

    Aim - To evaluate the effects of β blockers used in ophthalmology on the release of histamine from mixed cell preparations containing human leucocytes and basophils. Methods - A mixed leucocyte and basophil preparation was obtained from venous blood of healthy non-atopic volunteers. Cell

  7. Polymer membrane electrodes for sensitive potentiometric determination of beta-blockers.

    Science.gov (United States)

    Wassil, Anwar A; Farag, Abd El-Ftaah Bastawy; Moukdad, Fatma A

    2007-01-01

    The construction of PVC matrix-type beta-blockers (sotalol, carvedilol, and betaxolol) ion selective electrodes and their use for direct potentiometry of their respective species are described. The proposed sensors are based on the complex ion associates of beta-blockers with tungstophosphate (TP) and Ammonium Reineckate (Rein) ionophoris in poly vinyl chloride membrane (PVC) with Dioctylphthalate (DOP) plasticizer. The four electrodes (Beta-TP), (Sota-TP), (Carve-TP), and (Cave-Rein) show stable potential response with near Nernstian slope of 50.8, 33.7, 32.35, and 33 mv per decade, range of concentration 10-2-10-7 M beta-blockers. Selectivity coefficients data obtained for 11 different organic and inorganic ions are presented. The electrodes have fast response time (30 and 40 s) and were used over wide range of pH 4.5-8.5. Validation of the method according to the quality assurance standers shows suitability of proposed sensors for use in the quality control assessment of these drugs. The results obtained for the determination of beta-blockers with the proposed electrodes show average recoveries of 100.78% and a mean standard deviation of +/-1.2. The nominal are obtained. The data agree well with those obtained by standard methods.

  8. Calcium channel blockers and cancer : a risk analysis using the UK Clinical Practice Research Datalink (CPRD)

    NARCIS (Netherlands)

    Grimaldi-Bensouda, Lamiae; Klungel, Olaf; Kurz, Xavier; de Groot, Mark C H; Maciel Afonso, Ana S; de Bruin, Marie L; Reynolds, Robert; Rossignol, Michel

    2016-01-01

    OBJECTIVE: The evidence of an association between calcium channel blockers (CCBs) and cancer is conflicting. The objective of the present study was to evaluate the risk of cancer (all, breast, prostate and colon cancers) in association with exposure to CCB. METHODS: This is a population-based cohort

  9. Calcium channel blockers and cancer : A risk analysis using the UK Clinical Practice Research Datalink (CPRD)

    NARCIS (Netherlands)

    Grimaldi-Bensouda, Lamiae; Klungel, Olaf; Kurz, Xavier; De Groot, Mark C H; Afonso, Ana S Maciel; De Bruin, Marie L.; Reynolds, Robert; Rossignol, Michel

    2016-01-01

    OBJECTIVE: The evidence of an association between calcium channel blockers (CCBs) and cancer is conflicting. The objective of the present study was to evaluate the risk of cancer (all, breast, prostate and colon cancers) in association with exposure to CCB. METHODS: This is a population-based cohort

  10. Radioprotective effect of calcium channel blockers against late rectal bleeding in prostate cancer.

    Science.gov (United States)

    Massaccesi, Mariangela; Ippolito, Edy; Deodato, Francesco; Cilla, Savino; Digesù, Cinzia; Macchia, Gabriella; Caravatta, Luciana; Picardi, Vincenzo; Mattiucci, Gian Carlo; Di Lallo, Alessandra; Cuscunà, Daniele; Cellini, Numa; Valentini, Vincenzo; Morganti, Alessio G

    2014-05-01

    This study was done to assess the impact of clinical factors and in particular the use of drugs for concomitant illnesses on late radiation-induced rectal bleeding in patients with prostate cancer. Patients with histologically proven prostate adenocarcinoma treated with radical radiotherapy and followed up for at least 6 months were selected. The correlation between late rectal bleeding and a number of factors was investigated by univariate and multivariate analysis. A total of 278 patients who underwent radiotherapy at our institution between October 2002 and May 2011 were selected. At univariate analysis, delivery of radiation doses higher than 70 Gy and use of angiotensin-converting enzyme inhibitors were associated with a higher incidence of rectal bleeding. Conversely, patients who used calcium channel blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5 %, p = 0.043). At multivariate analysis, use of calcium channel blockers was found to have a protective effect with a hazard ratio of 0.3 (95 % CI 0.12-0.96). Delivery of higher radiation doses was associated with an increased risk of rectal bleeding (hazard ratio 3.02, 95 % CI 1.23-7.38). Use of calcium channel blockers during and after radiotherapy treatment might have a protective effect against late rectal bleeding. If these results are reconfirmed by larger clinical series, calcium channel blockers may be tested as radioprotector agents in clinical trials.

  11. The pharmaco-economics of peri-operative beta-blocker and statin ...

    African Journals Online (AJOL)

    We conducted a pharmaco-economic analysis of the prospective peri-operative studies of beta-blocker and statin administration for major elective non-cardiac surgery, using the Discovery Health claims costs for 2004. This analysis shows that acute peri-operative beta-blockade and statin therapy could result in a cost ...

  12. Structural adaptation to ischemia in skeletal muscle: effects of blockers of the renin-angiotensin system

    NARCIS (Netherlands)

    Scheidegger, K. J.; Nelissen-Vrancken, M. H.; Leenders, P. J.; Daemen, M. J.; Smits, J. F.; Wood, J. M.

    1997-01-01

    To investigate the effects of long-term treatment with blockers of the renin-angiotensin system on capillarization and growth of fibers in ischemic hind-limb muscles and in muscles under normal growth conditions. Ischemia was induced by partial ligation of the left common iliac artery. Ischemia

  13. Allergy, histamine 1 receptor blockers, and the risk of multiple sclerosis.

    Science.gov (United States)

    Alonso, Alvaro; Jick, Susan S; Hernán, Miguel A

    2006-02-28

    It is unclear whether allergic diseases are associated with multiple sclerosis (MS), but histamine 1 receptor blockers, used in the treatment of allergic conditions, decreased the severity of experimental autoimmune encephalomyelitis (an animal model of MS). To assess the association of allergy history and use of histamine 1 receptor blockers with the risk of MS. Using a case-control study nested in the United Kingdom-based General Practice Research Database cohort, the authors identified 163 incident cases of MS with at least 3 years of follow-up before their first symptoms (index date). Up to 10 controls matched to the cases by age, sex, general practice, and time in the cohort were selected. Previous history of allergic disease and use of histamine 1 receptor blockers in the 3 years before the index date were assessed through computerized medical records. History of any allergic condition in the 3 years before the index date was not associated with MS risk (adjusted odds ratio [OR] 1.2, 95% CI 0.8 to 1.8). However, use of sedating histamine 1 receptor blockers was associated with decreased MS risk (adjusted OR 0.2, 95% CI 0.1 to 0.8). These results do not support a strong link between allergic conditions and multiple sclerosis (MS) risk but suggest a possible beneficial effect of antihistamines on the onset of MS.

  14. Interaction among hERG channel blockers is a potential mechanism of death in caffeine overdose.

    Science.gov (United States)

    Zheng, Jifeng; Zhao, Wei; Xu, Kai; Chen, Qingmao; Chen, Yingying; Shen, Yueliang; Xiao, Liping; Jiang, Liqin; Chen, Yuan

    2017-04-05

    Caffeine overdose death is due to cardiac arrest, but its mechanism has not been explored in detail. In this study, our data showed that caffeine significantly prolonged the heart rate-corrected QT interval (QTc) of rabbits in vivo (PCaffeine was also found to be a hERG channel blocker with an IC 50 of 5.04mM (n=5). Although these two findings likely link caffeine overdose death with hERG channel blockade, the amount of caffeine consumption needed to reach the IC 50 is very high. Further study demonstrated that addition another hERG blocker could lower the consumption of caffeine significantly, no matter whether two hERG blockers share the same binding sites. Our data does not rule out other possibility, however, it suggests that there is a potential causal relationship between caffeine overdose death with hERG channel and the interaction among these hERG blockers. Published by Elsevier B.V.

  15. Beta-Blockers and the Kidney: Implications for Renal Function and Renin Release.

    Science.gov (United States)

    Epstein, Murray; And Others

    1985-01-01

    Reviews and discusses current information on the human renal response as related to beta-blockers (antihypertension agents). Topic areas considered include cardioselectivity, renal hemodynamics, systemic hemodynamics, changes with acute and chronic administration, influence of dose, and others. Implications and an 11-item multiple-choice self-quiz…

  16. Muscle cramps and elevated serum creatine phosphokinase levels induced by beta-adrenoceptor blockers.

    Science.gov (United States)

    Imai, Y; Watanabe, N; Hashimoto, J; Nishiyama, A; Sakuma, H; Sekino, H; Omata, K; Abe, K

    1995-01-01

    We have assessed the propensity of beta-adrenoceptor blockers to cause muscle cramps and to raise the serum creatine phosphokinase (CPK) level in 78 patients with essential hypertension. After a control period, a beta-adrenoceptor blocker without intrinsic sympathomimetic activity (ISA; propranolol, metoprolol or arotinolol) was administered for three months. Thereafter, the patients were randomised to receive a beta-adrenoceptor blocker with ISA (pindolol or carteolol) for three months or a beta-adrenoceptor blocker without ISA for a further three months. This pattern was continued until all beta-adrenoceptor blockers had been given. At the end of each period, CPK and CPK-MB levels were measured. Of the 78 subjects, muscle cramps occurred in 27 during treatment with pindolol and 32 during treatment with carteolol. No complaints were made by subjects treated with propranolol and arotinolol, but muscle cramps were reported in 2 treated with metoprolol. While muscle cramps were caused both by pindolol and carteolol in 16 subjects, they were caused by either of these drugs in the remainder of the subjects. Muscle cramp occurred mainly in the calves when the patients were in bed at night. Serum CPK and CPK-MB levels increased significantly during treatment with pindolol (control period vs pindolol, CPK = 96 vs 133 IU.ml-1, CPK-MB = 14 vs 18 IU.ml-1) or carteolol (CPK = 117 IU.ml-1, CPK-MB = 18 IU.ml-1) while the levels during treatment with propranolol, arotinolol and metoprolol did not change from those in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Calcium-channel blockers for the prevention of stroke: from scientific evidences to the clinical practice

    Directory of Open Access Journals (Sweden)

    S. Taddei

    2013-05-01

    Full Text Available AIM OF THE REVIEW The present review aims to analyze the role of calcium-channel blockers, and particularly newer molecules, as first-line therapy for cerebrovascular disease. BACKGROUND Stroke is the leading cause of disability in the general population. Among traditional cardiovascular risk factors, hypertension has a key role in the genesis of both hemorrhagic and ischemic stroke and a direct correlation exists between blood pressure values and the risk of stroke. Moreover, blood pressure reduction has been demonstrated to be the most important route to reduce stroke incidence and recurrence. However, the mere reduction of blood pressure values does not normalize the cardiovascular risk of the hypertensive patient. It is therefore necessary to use drug classes that beyond their blood pressure-lowering effect have also an additional effect in terms of organ protection. Among these, calcium-channel blockers have a crucial profile. Firstly, they are effective in inducing left ventricular hypertrophy regression, with a strength at least equal to that of ACE-inhibitors. Secondly, they have an antithrombotic and an endothelium-protecting effect, mediated by their antioxidant activity. Finally, calcium-channel blockers are the most powerful drugs in preventing vascular remodeling. For these reasons this drug class has probably the strongest antiatherosclerotic effect, and it is the first-choice treatment mainly for cerebrovascular disease. Among different available calcium-channel blockers, the newer ones seem to possess pharmacokinetic characteristics allowing a more homogeneous 24 hours coverage as compared to older molecules, and preliminary data seem to suggest a greater beneficial effect also on left ventricular hypertrophy and lower incidence of side effects. CONCLUSIONS Although blood pressure reduction is the main tool to reduce cerebrovascular risk in hypertensive patients, some drug classes, such as calciumchannel blockers, seem to provide

  18. Beta-blocker use and fall risk in older individuals: Original results from two studies with meta-analysis.

    Science.gov (United States)

    Ham, Annelies C; van Dijk, Suzanne C; Swart, Karin M A; Enneman, Anke W; van der Zwaluw, Nikita L; Brouwer-Brolsma, Elske M; van Schoor, Natasja M; Zillikens, M Carola; Lips, Paul; de Groot, Lisette C P G M; Hofman, Albert; Witkamp, Renger F; Uitterlinden, André G; Stricker, Bruno H; van der Velde, Nathalie

    2017-10-01

    To investigate the association between use of β-blockers and β-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism - and fall risk. Data from two prospective studies were used, including community-dwelling individuals, n = 7662 (the Rotterdam Study) and 2407 (B-PROOF), all aged ≥55 years. Fall incidents were recorded prospectively. Time-varying β-blocker use was determined using pharmacy dispensing records. Cox proportional hazard models adjusted for age and sex were applied to determine the association between β-blocker use, their characteristics - selectivity, lipid solubility, ISA and CYP2D6 enzyme metabolism - and fall risk. The results of the studies were combined using meta-analyses. In total 2917 participants encountered a fall during a total follow-up time of 89 529 years. Meta-analysis indicated no association between use of any β-blocker, compared to nonuse, and fall risk, hazard ratio (HR) = 0.97 [95% confidence interval (CI) 0.88-1.06]. Use of a selective β-blocker was also not associated with fall risk, HR = 0.92 (95%CI 0.83-1.01). Use of a nonselective β-blocker was associated with an increased fall risk, HR = 1.22 (95%CI 1.01-1.48). Other β-blocker characteristics including lipid solubility and CYP2D6 enzyme metabolism were not associated with fall risk. Our study suggests that use of a nonselective β-blocker, contrary to selective β-blockers, is associated with an increased fall risk in an older population. In clinical practice, β-blockers have been shown effective for a variety of cardiovascular indications. However, fall risk should be considered when prescribing a β-blocker in this age group, and the pros and cons for β-blocker classes should be taken into consideration. © 2017 The British Pharmacological Society.

  19. Application of first-derivative, ratio derivative spectrophotometry, TLC-densitometry and spectrofluorimetry for the simultaneous determination of telmisartan and hydrochlorothiazide in pharmaceutical dosage forms and plasma.

    Science.gov (United States)

    Bebawy, Lories I; Abbas, Samah S; Fattah, Laila A; Refaat, Heba H

    2005-10-01

    Four sensitive methods are described for the direct determination of telmisartan (TELM) and hydrochlorothiazide (HCT) in combined dosage forms without prior separation. The first method is a first derivative spectophotometry (1D) using a zero- crossing technique of measurement at 241.6 and 227.6 nm for TELM and HCT, respectively. The second method is the first derivative of ratio spectrophotometry (1DD) where the amplitudes were measured at 242.7 nm for TELM and 274.9 nm for HCT. The third method is based on TLC separation of the two drugs followed by the densitometric measurements of their spots at 295 and 225 nm for TELM and HCT, respectively. The separation was carried out on silica gel 60 F254 using butanol: ammonia 25% (8:2 v/v) as mobile phase. The fourth method is spectrofluorimetric determination of TELM, depending on measuring the native fluorescence of the drug in 1 M sodium hydroxide at lambda excitation 230 nm and emission at 365 nm. The proposed methods were applied successfully for the determination of the two drugs in bulk powder and in pharmaceutical formulations. The spectrofluorimetric method was utilized for the analysis of TELM in human plasma.

  20. Trends in Prescription and Determinants of Persistence to Antihypertensive Therapy : The PAPEETE Study.

    Science.gov (United States)

    Costa, Francesco Vittorio; Degli Esposti, Luca; Cerra, Carlo; Veronesi, Chiara; Buda, Stefano

    2009-12-01

    To assess trends in prescriptions, determinants and timing of treatment discontinuation and/or changes in antihypertensive drug therapy in a cohort of hypertensive patients living in Pavia, a city in the north of Italy. The cohort included 61 493 patients aged ≥18 years who received their first antihypertensive drug prescription (monotherapy, fixed or extemporaneous combination) during the period 2003-6. Patients were classified as 'persistent' if 12 months after the beginning of treatment they were still taking a regular therapy (same drug = 'same therapy users', added one or more drugs = 'add-on therapy users', different drug = 'switchers'). Otherwise, they were classified as 'non-persistent' (stopping therapy after the first prescription = 'occasional users'; stopping treatment early = 'stoppers'; taking medicines in an erratic fashion = 'intermittent users'). ACE inhibitors were the most frequently prescribed drugs (22.8%), followed by β-adrenoceptor antagonists (β-blockers) [14.3%], diuretics (13.9%), Ca(2+) antagonists (11.4%) and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) [9.3%]. After 12 months, persistent patients were only 11.2% (same therapy users 6.7%, switchers 3.2%, add-on therapy users 1.3%). Non-persistent patients were 88.8% (35.3% occasional users, 20.6% stoppers, 32.8% intermittent users). Patient-related predictors of persistence were older age, male sex, concomitant treatment with antidiabetic and hypolipidaemic drugs and previous hospitalizations for cardiovascular events. Highest level of persistence was seen in patients starting with ARBs (18.8%), followed by ACE inhibitors (11.4%), β-blockers (11.0%), Ca(2+) antagonists (10.8%) and diuretics (3.0%). Among ARBs, considering separately monotherapy and fixed-combination therapy, highest level of persistence was observed in patients starting with candesartan, irbesartan, valsartan and telmisartan given in monotherapy, and with valsartan and

  1. Beta-blockers and health-related quality of life in patients with peripheral arterial disease and COPD.

    Science.gov (United States)

    van Gestel, Yvette R B M; Hoeks, Sanne E; Sin, Don D; Stam, Henk; Mertens, Frans W; Bax, Jeroen J; van Domburg, Ron T; Poldermans, Don

    2009-01-01

    Beta-blockers are frequently withheld in patients with cardiovascular disease who also have chronic obstructive pulmonary disease (COPD) because of concerns that they might provoke bronchospasm and cause deterioration in health status. Although beta1-selective beta-blockers are associated with reduced mortality in COPD patients, their effects on health status are unknown. The aim of this study was to investigate the relationship between beta-blockers and health-related quality of life (HRQOL) in patients with peripheral arterial disease and COPD. Of the original cohort of 3371 vascular surgery patients, 1310 had COPD of whom 469 survived during long-term follow-up. These COPD patients were sent the Short Form-36 (SF-36) health-related quality of life questionnaire, which was completed and returned by 326 (70%) patients. No significant differences in any of the SF-36 domains were observed between COPD patients who did and did not use beta-blockers (p > 0.05 for all). Furthermore, beta-blockers were not associated with any impairment in HRQOL among patients with COPD. Beta-blockers had no material impact on the HRQOL of patients with peripheral arterial disease who also had COPD. This suggests that beta-blockers can, in most circumstances, be administered to patients with COPD without impairment in HRQOL.

  2. Impact of beta-blocker treatment and nutritional status on glycemic response during exercise in patients with type 2 diabetes.

    Science.gov (United States)

    Ferland, Annie; Brassard, Patrice; Croteau, Sara; Lemieux, Simone; Bergeron, Jean; Lacroix, Stéphanie; Fournier, Lison; Poirier, Paul

    2007-01-01

    Most individuals with type 2 diabetes are affected by hypertension and thus have higher risk of cardiac complications. In addition to behavioural modifications, such as healthy food choices and regular physical activity, beta-blocker treatment may be considered to reduce morbidity and mortality, especially after a cardiovascular event. However, this medication is generally associated with a deleterious impact on glucose metabolism. The objective of the study was to assess the impact of beta-blocker treatment on glucose response during exercise in patients with type 2 diabetes, free of cardiovascular complications. Ten sedentary men, treated with diet and/or hypoglycemic agents have performed four exercise sessions at 60% of their V O2peak, in the fasted state or 2 hours following a standardized breakfast, with and without beta-blockers (atenolol 100 mg id for five consecutive days). Blood samples were drawn during the resting period, at 15-min intervals during the exercise session and during the recovery period. A reduction of blood glucose levels was observed following the exercise session in the postprandial state (48% and 44% reduction with and without beta-blockers respectively; P exercise performed in the fasted state had a minimal impact on glucose and insulin levels, whether with or without beta-blockers. beta-blocker treatment was not associated with increased baseline blood glucose or insulin levels in the fasted or the postprandial situation. Dietary status has a more important impact on plasma glucose and insulin modulation than short-term use of beta-blockers.

  3. Comparison the Efficacy of Four Different Alpha Blockers in the Treatment of Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Fatih Fırat

    2011-05-01

    Full Text Available Aim: Benign prostatic hyperplasia (BPH also known as nodular hyperplasia, benign enlargement of the prostate refers to the increase in size of the prostate in middle aged and elderly men. Although four different types of specific alpha blocker have been used in the treatment of BPH it remains controversial that which alpha adrenergic blocker is effective than others. The aim of this study is to compare the efficacy of 4 different alpha blockers agents on the treatment of BPH. Material and Methods: Between June 2005 and December 2008 a total of 135 consecutive patients with diagnosed of BPH were evaluated in our clinic. Patients were randomized into four groups according to alpha blocker types as fallows: group I, doxazosin 4 mg; group II, tamsulosin 0.4 mg; group III, terazosin 5 mg; and group IV, alfuzosin 10 mg. All patients were followed up with International Prostatic Symptom Score (IPSS, maximal urinary flow rates (Qmax and adverse effects were determined at baseline and again at least 3 months as efficacy parameters. Results: The mean age of the patients were 59.8±5.4 years, 58.9±6.4 years, 58.7±5.1 years, and 59.2±5.5 years in group I, group II, group III, and group IV, respectively (p>0.05. After 3 months treatment with alpha blockers the improvements in IPSS were found as 2.73, 3.73, 3.55 and 4.44 in group I, group II, group III, and group IV, respectively. Maximum urine flow rates increased as 2.81 ml/sec, 3.24 ml/sec, 3.88 ml/sec and 4.49 ml/sec in group I, group II, group III, and group IV, respectively. However, among 4 alpha blockers statistically significant difference was found only between doxazosin and alfuzosin groups according to uroflowmetry and IPSS results. According to these results, when compared adverse effect, the significant difference was observed only in tamsulosine group. Conclusions: As a result we can say that except retrograde ejaculation in tamsulosine group, adverse effects are not different between the

  4. Alpha blockers in the management of ureteric lithiasis: A meta-analysis.

    Science.gov (United States)

    Raison, Nicholas; Ahmed, Kamran; Brunckhorst, Oliver; Dasgupta, Prokar

    2017-01-01

    Effective medical expulsion for ureteric stones with α-blockers offers numerous advantages over surgical alternatives. However, its effectiveness remains uncertain and with the publication of new trial data, the available evidence requires reappraisal. The aim of this study was to assess the efficacy of α-blockers the management of ureteric lithiasis. A systematic review of the literature, with predefined search criteria, was conducted using PubMed and Embase. All randomised trials comparing α-blocker monotherapy to placebo or standard therapy were included. Stone expulsion rate was the primary outcome measure. Secondary outcome measures were time to stone expulsion, analgesic usage and pain scores. Subgroup analyses assessed individual adrenergic antagonists and variations in standard therapy. Sensitivity analysis was based on stone location, stone size, Cochrane Risk of Bias score and study protocol. Summary effects were calculated using a random-effect model and presented as Relative risks (RR) and mean differences (MD) for dichotomous and continuous outcome measures, respectively. Sixty-seven studies randomising 6654 patients were included in the meta-analysis. Stone expulsion rates improved with α-blockers (RR, 1.49; 95% CI 1.38-1.61). Contrast enhanced funnel showed evidence of publication bias. Stone expulsion time was 3.99 days (CI -4.75 to -3.23) shorter with α-blockers. Similarly, patients required 106.53 mg [CI -148.20 to -64.86] less diclofenac compared with control/placebo, and had 0.80 [CI -1.07 to -0.54] fewer pain episodes. Visual Analogue Scores were also reduced, -2.43 [CI -3.87 to -0.99]. All formulations of α-antagonists all demonstrated beneficial effects over conservative treatment/placebo. Sensitivity analysis demonstrated significant effects of stone location, stone size and study design. Despite the opposing results of recently published trial, current evidence continues to demonstrate a potential benefit of α-blocker treatment

  5. Antiproliferative effects of β-blockers on human colorectal cancer cells.

    Science.gov (United States)

    Coelho, M; Moz, M; Correia, G; Teixeira, A; Medeiros, R; Ribeiro, L

    2015-05-01

    Colon cancer is the fourth and third most common cancer, respectively in men and women worldwide and its incidence is on the increase. Stress response has been associated with the incidence and development of cancer. The catecholamines (CA), adrenaline (AD) and noradrenaline (NA), are crucial mediators of stress response, exerting their effects through interaction with α- and β-adrenergic receptors (AR). Colon cancer cells express β-AR, and their activation has been implicated in carcinogenesis and tumor progression. Interest concerning the efficacy of β-AR blockers as possible additions to cancer treatment has increased. The aim of this study was to investigate the effect of several AR agonists and β-blockers following cell proliferation of HT-29 cells, a human colon adenocarcinoma cell line. For this purpose, HT-29 cells were incubated in the absence (control) or in the presence of the AR-agonists, AD, NA and isoprenaline (ISO) (0.1-100 µM) for 12 or 24 h. The tested AR agonists revealed proliferative effects on HT-29 cells. In order to study the effect of several β-blockers following proliferation induced by AR activation, the cells were treated with propranolol (PRO; 50 µM), carvedilol (CAR; 5 µM), atenolol (ATE; 50 µM), or ICI 118,551 (ICI; 5 µM) for 45 min prior, and simultaneously, to incubation with each of the AR agonists, AD and ISO, both at 1 and 10 µM. The results suggested that adrenergic activation plays an important role in colon cancer cell proliferation, most probably through β-AR. The β-blockers under study were able to reverse the proliferation induced by AD and ISO, and some of these blockers significantly decreased the proliferation of HT-29 cells. The elucidation of the intracellular pathways involved in CA-induced proliferation of colon cancer cells, and in the reversion of this effect by β-blockers, may contribute to identifying promising strategies in cancer treatment.

  6. Assessment of serum lipid metabolism index and cytokine levels in patients with type 2 diabetes mellitus complicated by coronary heart disease after telmisartan combined with lipid-lowering drug treatment

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2017-07-01

    Full Text Available Objective: To study the effect of telmisartan combined with lipid-lowering drug therapy on serum lipid metabolism index and cytokine levels in patients with type 2 diabetes mellitus complicated by coronary heart disease. Methods: A total of 106 patients with type 2 diabetes mellitus complicated by coronary heart disease who were treated in our hospital between September 2013 and October 2016 were collected and then divided into the control group (n=55 who received conventional treatment + lipid-lowering drug treatment and the observation group (n=51 who received conventional treatment + lipid-lowering drug + telmisartan treatment after the therapies were reviewed. Before and after treatment, serum levels of lipid metabolism indexes, inflammatory mediators and oxidative stress indexes were compared between two groups of patients. Results: Before treatment, the differences in serum levels of lipid metabolism indexes, inflammatory mediators and oxidative stress indexes were not statistically significant between two groups of patients. After treatment, serum TG and LDL-C levels in observation group were lower than those in control group while HDL-C level was higher than that in control group; serum inflammatory mediators IL-6, IL-8, HMGB1 and TNF-α levels were lower than those in control group; serum oxidative stress indexes MDA and ROS levels were lower than those in control group while GSH-Px level was higher than that in control group. Conclusion: Telmisartan combined with lipid-lowering drug therapy can effectively optimize the lipid metabolism and reduce the systemic inflammatory response and oxidative stress response in patients with type 2 diabetes mellitus complicated by coronary heart disease.

  7. Calcium channel blocker enhances beneficial effects of an angiotensin II AT1 receptor blocker against cerebrovascular-renal injury in type 2 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Kazi Rafiq

    Full Text Available Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-A(y mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB disruption, albuminuria, glomerular sclerosis and podocyte injury. These brain and renal injuries were associated with increased gene expression of NADPH oxidase components, NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day reduced blood pressure in saline-drinking KK-A(y mice and attenuated cognitive decline, BBB disruption, glomerular injury and albuminuria, which were associated with a reduction of NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Furthermore, a suppressive dose of azelnidipine (3 mg/kg/day exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associated cerebrovascular-renal protective effects through suppression of NADPH oxidase-dependent oxidative stress in type 2 diabetes.

  8. Use of statins and beta-blockers after acute myocardial infarction according to income and education

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Nørgaard; Gislason, Gunnar H; Rasmussen, Søren

    2007-01-01

    OBJECTIVE: To study the initiation of and long-term refill persistency with statins and beta-blockers after acute myocardial infarction (AMI) according to income and education. DESIGN AND SETTING: Linkage of individuals through national registers of hospitalisations, drug dispensation, income...... and education. PARTICIPANTS: 30 078 patients aged 30-74 years surviving first hospitalisation for AMI in Denmark between 1995 and 2001. MAIN OUTCOME MEASURES: Initiation of statin or beta-blocker treatment (out-patient claim of prescriptions within 6 months of discharge) and refill persistency (first break...... in treatment lasting at least 90 days, and re-initiation of treatment after a break). RESULTS: When simultaneously estimating the effect of income and education on initiation of treatment, the effect of education attenuated and a clear income gradient remained for both drugs. Among patients aged 30-64 years...

  9. Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies

    DEFF Research Database (Denmark)

    Bergman, Jorieke E H; Lutke, L Renée; Gans, Rijk O B

    2018-01-01

    the risk of specific congenital anomalies in offspring. METHODS: A population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data...... compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies. RESULTS: The signals from the literature (congenital heart defects, oral clefts, neural......-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm...

  10. Facile diverted synthesis of pyrrolidinyl triazoles using organotrifluoroborate: discovery of potential mPTP blockers.

    Science.gov (United States)

    Jung, Sun hwa; Choi, Kihang; Pae, Ae Nim; Lee, Jae Kyun; Choo, Hyunah; Keum, Gyochang; Cho, Yong Seo; Min, Sun-Joon

    2014-12-21

    This article describes the rapid and diversified synthesis of pyrrolidinyl triazoles for the discovery of mitochondrial permeability transition pore (mPTP) blockers. The 1,3-dipolar cycloaddition of ethynyl trifluoroborate with azidopyrrolidine produced a key intermediate, triazolyl trifluoroborate 4, which subsequently underwent a Suzuki-Miyaura coupling reaction to afford a series of 1,4-disubstituted triazoles 2. Subsequent biological evaluation of these derivatives indicated 2ag and 2aj as the most potent mPTP blockers exhibiting excellent cytochrome P450 (CYP) stability when compared to the previously reported oxime analogue 1. The present work clearly demonstrates that a 1,2,3-triazole can be used as a stable oxime surrogate. Furthermore, it suggests that late-stage diversification through coupling reactions of organotrifluoroborates is suitable for the rapid discovery of biologically active molecules.

  11. IRBESARTAN IN THE CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2015-09-01

    Full Text Available Only few hypertensive patients are treated effectively despite of the variety of antihypertensive drugs. There is a linear relationship between blood pressure levels and the risk of complications (myocardial infarction, stroke, chronic heart and renal failure. Angiotensin receptor blockers are the first-line drugs for initial therapy of uncomplicated hypertension. Irbesartan is one of the most studied angiotensin receptor blockers. Data supporting the high antihypertensive and nephroprotection efficacy of irbesartan as well as its ability to reduce cardiovascular risk in hypertensive patients are presented.

  12. IRBESARTAN IN THE CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2014-01-01

    Full Text Available Only few hypertensive patients are treated effectively despite of the variety of antihypertensive drugs. There is a linear relationship between blood pressure levels and the risk of complications (myocardial infarction, stroke, chronic heart and renal failure. Angiotensin receptor blockers are the first-line drugs for initial therapy of uncomplicated hypertension. Irbesartan is one of the most studied angiotensin receptor blockers. Data supporting the high antihypertensive and nephroprotection efficacy of irbesartan as well as its ability to reduce cardiovascular risk in hypertensive patients are presented.

  13. Syncope caused by iatrogenic hyperkalemia.

    Science.gov (United States)

    Giancaspro, Giuseppe; Suppa, Marianna; Genuini, Igino; Caselli, Stefano; Fedele, Francesco

    2009-01-01

    Symptomatic bradycardia in the emergency department may have several causes (excessive vagal tone, drug toxicity, acute myocardial ischemia, sick sinus syndrome, heart block, and electrolyte imbalance); among these, hyperkalemia may develop as a complication of chronic medical treatment with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and must be considered in the early approach to the bradyarrhythmic patient with possible electrocardiographic signs of hyperkalemia. We report a case of an 87-year-old woman with a clinical history of chronic angiotensin-receptor blocker consumption that led her to dangerous bradyarrhythmia, cardiogenic syncope, and risk of sudden cardiac death.

  14. Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance.

    Science.gov (United States)

    Cohen-Solal, Alain; Jacobson, Arnold F; Piña, Ileana L

    2017-11-01

    Extent of cardiac sympathetic activation can be estimated from physiological parameters, blood biomarkers, and imaging findings. This study examined the prognostic value of three markers of sympathetic activity and their relationship to beta blocker dose in heart failure patients. A post hoc analysis of 858 heart failure subjects in the ADMIRE-HF trial was performed. Variables related to sympathetic activity were plasma norepinephrine, baseline heart rate, the heart to mediastinum (H/M) ratio of 123 I-mIBG uptake, and beta blocker dose. Univariate and multivariate analyses for occurrence of mortality (all-cause and cardiac) and arrhythmic events were performed. Beta blocker dose was significantly related to age, heart rate, b-type natriuretic peptide (negatively), body mass index, body weight and plasma norepinephrine. Univariate predictors of all-cause and cardiac mortality were baseline heart rate (χ 2  = 4.5, P = 0.029 and χ 2  = 5 .2, P = 0.022, respectively), plasma norepinephrine level (χ 2  = 8.9, P = 0.0006 and χ 2  = 8.6, P = 0.003, respectively), and H/M (χ = 22.4, P heart rate, mean heart rate >67 b.p.m. was associated with significantly higher cardiac mortality. Higher beta blocker dose was associated with lower mortality, but of the variables associated with sympathetic activity examined, cardiac 123 I-mIBG uptake was the most powerful prognostic marker in heart failure patients. Elevated heart rate was associated with greater risk for cardiac death. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  15. Interactions between calcium channel blockers and the anticonvulsants carbamazepine and phenytoin.

    Science.gov (United States)

    Bahls, F H; Ozuna, J; Ritchie, D E

    1991-05-01

    We describe a retrospective analysis of the frequency of adverse interactions between calcium channel blockers and anticonvulsant drugs (phenytoin and carbamazepine) in a series of 43 patients. Ten patients receiving carbamazepine and three patients receiving phenytoin exhibited symptoms or signs of toxicity. Toxicity occurred with both diltiazem and verapamil, but not with nifedipine. These results emphasize the need for careful clinical and laboratory monitoring of patients receiving both classes of medication.

  16. Growth inhibition of human cancer cells in vitro by T-type calcium channel blockers.

    Science.gov (United States)

    Lee, Jae Yeol; Park, Seong Jun; Park, Sung Jun; Lee, Min Joo; Rhim, Hyewhon; Seo, Seon Hee; Kim, Ki-Sun

    2006-10-01

    This paper describes the preliminary biological results that novel T-type calcium channel blockers inhibit the growth of human cancer cells by blocking calcium influx into the cell, based on unknown mechanism on the cell cycle responsible for cellular proliferation. Among the selected compounds from compound library, compound 9c (KYS05041) was identified to be nearly equipotent with Cisplatin against some human cancers in the micromolar range.

  17. Recent developments in HPLC analysis of β-blockers in biological samples.

    Science.gov (United States)

    Saleem, Kishwar; Ali, Imran; Kulsum, Umma; Aboul-Enein, Hassan Y

    2013-09-01

    β-Adrenergic blockers represent a very important class of drugs that are used worldwide for treating various cardiac diseases. The present article describes the state-of-the art of analyses of β-adrenergic blockers using high-performance liquid chromatography (HPLC). Sample preparation techniques such as liquid-liquid extraction, solid-phase extraction and solid-phase microextraction have been discussed, which are essential prior to HPLC analysis. Additionally, applications of liquid chromatography coupled with tandem mass spectrometry are included. HPLC methods have been reported to include 0.6-26 min as the run times and 0.01 ng/mL to 25 µg/mL as detection limits. The most commonly used columns were C18 with various buffers as the mobile phases, along with various organic modifiers. The optimization of HPLC conditions has been discussed. It has been observed that the reported methods are quite satisfactory for the analyses of β-adrenergic blockers in biological samples. Future perspectives in the hyphenation of solid-phase microextraction-nano-liquid chromatography-tandem mass spectrometry have also been highlighted to achieve detections at nanogram and picogram levels. The present article is very useful for academicians, scientists, drug and pharmaceutical personnel and government regulatory authorities.

  18. Management of untreatable ventricular arrhythmias during pharmacologic challenges with sodium channel blockers for suspected Brugada syndrome.

    Science.gov (United States)

    Poli, Stefano; Toniolo, Mauro; Maiani, Massimo; Zanuttini, Davide; Rebellato, Luca; Vendramin, Igor; Dametto, Ermanno; Bernardi, Guglielmo; Bassi, Flavio; Napolitano, Carlo; Livi, Ugolino; Proclemer, Alessandro

    2018-02-01

    Pharmacologic challenge with sodium channel blockers is part of the diagnostic workout in patients with suspected Brugada syndrome. The test is overall considered safe but both ajmaline and flecainide detain well known pro-arrhythmic properties. Moreover, the treatment of patients with life-threatening arrhythmias during these diagnostic procedures is not well defined. Current consensus guidelines suggest to adopt cautious protocols interrupting the sodium channel blockers as soon as any ECG alteration appears. Nevertheless, the risk of life-threatening arrhythmias persists, even adopting a safe and cautious protocol and in absence of major arrhythmic risk factors. The authors revise the main published case studies of sodium channel blockers challenge in adults and in children, and summarize three cases of untreatable ventricular arrhythmias discussing their management. In particular, the role of advanced cardiopulmonary resuscitation with extra-corporeal membrane oxygenation is stressed as it can reveal to be the only reliable lifesaving facility in prolonged cardiac arrest. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  19. β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon.

    Science.gov (United States)

    Richards, John R; Hollander, Judd E; Ramoska, Edward A; Fareed, Fareed N; Sand, I Charles; Izquierdo Gómez, María Manuela; Lange, Richard A

    2017-05-01

    Cocaine abuse remains a significant worldwide health problem. Patients with cardiovascular toxicity from cocaine abuse frequently present to the emergency department for treatment. These patients may be tachycardic, hypertensive, agitated, and have chest pain. Several pharmacological options exist for treatment of cocaine-induced cardiovascular toxicity. For the past 3 decades, the phenomenon of unopposed α-stimulation after β-blocker use in cocaine-positive patients has been cited as an absolute contraindication, despite limited and inconsistent clinical evidence. In this review, the authors of the original studies, case reports, and systematic review in which unopposed α-stimulation was believed to be a factor investigate the pathophysiology, pharmacology, and published evidence behind the unopposed α-stimulation phenomenon. We also investigate other potential explanations for unopposed α-stimulation, including the unique and deleterious pharmacologic properties of cocaine in the absence of β-blockers. The safety and efficacy of the mixed β-/α-blockers labetalol and carvedilol are also discussed in relation to unopposed α-stimulation.

  20. Agile Blocker and Clock Jitter Tolerant Low-Power Frequency Selective Receiver with Energy Harvesting Capability.

    Science.gov (United States)

    Hasan, Abul; Helaoui, Mohamed; Ghannouchi, Fadhel M

    2017-08-29

    In this article, a novel tunable, blocker and clock jitter tolerant, low power, quadrature phase shift frequency selective (QPS-FS) receiver with energy harvesting capability is proposed. The receiver's design embraces and integrates (i) the baseband to radio frequency (RF) impedance translation concept to improve selectivity over that of conventional homodyne receiver topologies and (ii) broadband quadrature phase shift circuitry in the RF path to remove an active multi-phase clock generation circuit in passive mixer (PM) receivers. The use of a single local oscillator clock signal with a passive clock division network improves the receiver's robustness against clock jitter and reduces the source clock frequency by a factor of N, compared to PM receivers using N switches (N≥4). As a consequence, the frequency coverage of the QPS-FS receiver is improved by a factor of N, given a clock source of maximum frequency; and, the power consumption of the whole receiver system can eventually be reduced. The tunable QPS-FS receiver separates the wanted RF band signal from the unwanted blockers/interferers. The desired RF signal is frequency down-converted to baseband, while the undesired blocker/interferer signals are reflected by the receiver, collected and could be energy recycled using an auxiliary energy harvesting device.

  1. Cochrane Corner: Antihypertensive efficacy of beta-1 selective beta blockers for primary hypertension.

    Science.gov (United States)

    Nogueira-Silva, Luís; Marques, Pedro Sousa; Lima, Maria João

    2017-05-01

    Beta blockers are commonly used to treat hypertension. This Cochrane systematic review assessed the effect of beta-1 selective beta blockers on blood pressure (BP), pulse pressure (PP), heart rate (HR) and withdrawal due to adverse effects in patients with primary hypertension. Fifty-six randomized placebo-controlled trials were included, with a total of 7812 patients. These drugs reduced systolic/diastolic BP by 10/8 mmHg, PP by 2 mmHg and HR by 11 bpm; no difference was found between treatment and placebo regarding withdrawal due to adverse effects. Differences in efficacy were observed between the various beta-1 selective beta blockers, which may be due to methodological differences in the trials. The choice of an antihypertensive drug should take into account not only its efficacy in reducing BP but also its tolerability, its efficacy in preventing cardiovascular events, and other factors such as undesirable metabolic effects. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats.

    Science.gov (United States)

    Ludens, J H; Clark, M A; Lawson, J A

    1995-06-01

    Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats were observed. Effects of K+ channel modulation on glomerular filtration rate and electrolyte excretion were studied using the adenosine-triphosphate- (ATP)-sensitive K+ channel blocker 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U-37883A) in conscious rats previously equipped with catheters for clearance studies. In saline-loaded rats, i.v. doses of U-37883A of 1.7, 5.0 and 15 mg/kg increased absolute and fractional Na+ excretion dose-dependently without changing K+ excretion. The glomerular filtration rate remained constant during diuresis. In water-loaded (hypotonic dextrose) rats, free-water clearance studies revealed that the ATP-sensitive K+ channel blocker significantly decreased an index of solute reabsorption (free-water clearance adjusted for chloride clearance) in the diluting segment during peak natriuretic activity. In addition, U-37883A significantly decreased the osmolality of renal papillary interstitial fluid, indicative of an effect in the medullary portion of the diluting segment. Together, these findings suggest that ATP-sensitive K+ channels, possibly those located at the apical boarder, play a pivotal role in Na+ reabsorption in the thick ascending limb of the loop of Henle.

  3. The effect of calcium channel blockers on prevention of preeclampsia in pregnant women with chronic hypertension.

    Science.gov (United States)

    Jiang, N; Liu, Q; Liu, L; Yang, W W; Zeng, Y

    2015-01-01

    Pregnant women with chronic hypertension are at increased risk for complications. This study aims to investigate whether calcium channel blockers plus low dosage aspirin therapy can reduce the incidence of complications during pregnancy with chronic hypertension and improve the prognosis of neonates. From March 2011 to June 2013, 33 patients were selected to join this trial according to the chronic hypertension criteria set by the Preface Bulletin of American College of Obstetricians and Gynecologists, (ACOG). Patients were administrated calcium channel blockers plus low-dosage aspirin and vitamin C. The statistic data of baseline and prognosis from the patients were retrospectively reviewed and compared. Blood pressure of patients was controlled by these medicines with average systolic pressure from 146.3 to 148.7 mmHg and average diastolic pressure from 93.8 to 97.9 mmHg; 39.4% patients complicated mild preeclampsia; however, none of them developed severe preeclampsia or eclampsia, or complicate placental abruption. 30.3% patients delivered at preterm labour; 84.8% patients underwent cesarean section. The neonatal average weight was 3,008 ± 629.6 g, in which seven neonatal weights were less than 2,500 g. All of the neonatal Apgar scores were 9 to 10 at one to five minutes. Small for gestational age (SGA) occurred in five (15%). Calcium channel blockers can improve the outcome of pregnancy women with chronic hypertension to avoid the occurrence of severe pregnancy complication or neonatal morbidity.

  4. L-Carnitine for the treatment of a calcium channel blocker and metformin poisoning.

    Science.gov (United States)

    St-Onge, Maude; Ajmo, Ian; Poirier, Diane; Laliberté, Martin

    2013-09-01

    The object of the current communication is to discuss the theory and the evidence for the use of L-carnitine in calcium channel blocker and metformin poisonings. A 68-year-old male known for hypertension and type II diabetes was admitted to the critical care unit of a community hospital following an overdose of amlodipine and metformin. The patient was intubated, ventilated, and hemodynamically supported with vasopressors. Despite calcium, glucagon, high-dose insulin (HDI), and lipid emulsion for calcium channel blocker and bicarbonate for metabolic acidosis, the patient remained hemodynamically unstable. The patient was considered too unstable to initiate continuous renal replacement therapy; and without access to extracorporeal life support, the administration of L-carnitine was administered as a last resort. One hour after L-carnitine, the norepinephrine requirements started to decrease, the patient began to improve and was subsequently extubated successfully without apparent sequelae in less than 4 days. L-Carnitine combined with HDI may have helped with the calcium channel blocker (CCB) poisoning by decreasing insulin resistance, promoting intracellular glucose transport, facilitating the metabolism of free fatty acids, and increasing calcium channel sensitivity. It may have also stimulated oxidative utilization of glucose instead of converting pyruvate into lactate and contributed to decrease lactate production with metformin poisoning.

  5. Effects of treatment with β-blocker and aldosterone antagonist on central and peripheral haemodynamics and oxygenation in cirrhosis

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander

    2011-01-01

    Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics and oxyg......Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics...

  6. HIGH SELECTIVE LONG-ACTING Β1-BLOCKER WITH A VASODILATING EFFECT NEBIVOLOL IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    V. P. Lupanov

    2012-01-01

    Full Text Available Review is devoted to the role of modern beta-blocker nebivolol in the treatment of stable ischemic heart disease (IHD. The mode of nebivolol anti-ischemic activity is considered, as well as its use particularities in IHD patients with different concomitant diseases. Nebivolol effects are compared with these of other beta-blockers and other antianginal drugs in terms of angina symptoms reduction, quality of life improvement and decrease in cardiovascular complications risk.

  7. HIGH SELECTIVE LONG-ACTING Β1-BLOCKER WITH A VASODILATING EFFECT NEBIVOLOL IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    V. P. Lupanov

    2015-12-01

    Full Text Available Review is devoted to the role of modern beta-blocker nebivolol in the treatment of stable ischemic heart disease (IHD. The mode of nebivolol anti-ischemic activity is considered, as well as its use particularities in IHD patients with different concomitant diseases. Nebivolol effects are compared with these of other beta-blockers and other antianginal drugs in terms of angina symptoms reduction, quality of life improvement and decrease in cardiovascular complications risk.

  8. Chiral separation of beta-blockers after derivatization with (-)-menthyl chloroformate by reversed-phase high performance liquid chromatography.

    Science.gov (United States)

    Kim, K H; Choi, P W; Hong, S P; Kim, H J

    1999-12-01

    Optimum conditions of chiral derivatization reaction of beta-blockers acebutolol, arotinolol, beta-xolol, bisoprolol, celiprolol, metoprolol and pindolol) with (-)-menthyl chloroformate were investigated for the resolution by HPLC. With more than 30 times molar excess of (-)-menthyl chloroformate chiral derivatization reactions were completed within one hour at room temperature except arotinolol and celiprolol. Diastereomeric derivatives of beta-blockers were well resolved on the ODS column using acetonitrile-methanol-water as a mobile phase.

  9. Barriers to Beta-Blocker Use and Up-Titration Among Patients with Heart Failure with Reduced Ejection Fraction.

    Science.gov (United States)

    Levitan, Emily B; Van Dyke, Melissa K; Loop, Matthew Shane; O'Beirne, Ronan; Safford, Monika M

    2017-12-01

    For patients with heart failure with reduced ejection fraction (HFrEF), guidelines recommend use of beta-blockers with gradual up-titration. However, many patients with HFrEF do not use beta-blockers and up-titration is rare. Our purpose was to identify and rank barriers to beta-blocker use and up-titration from the perspective of primary care physicians. We conducted 4 moderated, structured group discussions among 19 primary care physicians using the nominal group technique; 16 participants also completed a survey. Participants generated lists of barriers to beta-blocker use and up-titration among patients with HFrEF. Each participant had six votes with three votes assigned to the item ranked most important, two to the second most important item, and one to the third most important item. Investigators characterized items into themes. The percentage of available votes was calculated for each theme. Fifteen of 16 participating primary care physicians who completed the survey reported that management of beta-blockers was their responsibility. Treatment/side effects, particularly hypotension, were identified as the most important barrier for beta-blocker use (72% of available votes) followed by polypharmacy (11%), healthcare system barriers (10%), and comorbidities (6%). Barriers to up-titration included treatment/side effects (49% of available votes), patient communication/buy-in (21%), polypharmacy (13%), and healthcare system barriers (8%). Many barriers to guideline concordant use of beta-blockers among patients with HFrEF identified by primary care providers are not readily modifiable. Addressing these barriers may require development, testing, and dissemination of protocols for beta-blocker initiation and up-titration that are safe and appropriate in primary care.

  10. Effects of captopril, telmisartan and bardoxolone methyl (CDDO-Me) in ischemia-reperfusion-induced acute kidney injury in rats: an experimental comparative study.

    Science.gov (United States)

    Kocak, Cengiz; Kocak, Fatma Emel; Akcilar, Raziye; Bayat, Zeynep; Aras, Bekir; Metineren, Mehmet Huseyin; Yucel, Mehmet; Simsek, Hasan

    2016-02-01

    Renal ischemia-reperfusion (IR) injury is one of the most common causes of acute kidney injury. This study investigated the effects of captopril (CAP), telmisartan (TEL) and bardoxolone methyl (BM) in animals with renal IR injury. Adult male Wistar-Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60-min ischemia and a 120-min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) levels, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), asymmetric dimethylarginine (ADMA) levels, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator-activated receptor-ɣ (PPAR-ɣ), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide (NO) and ADMA levels, NF-κB, inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) expressions (P < 0.001). All tested drugs increased SOD activity, GSH-Px activity, TAS levels, TT levels, endothelial nitric oxide synthase (eNOS) expression, dimethylarginine dimethylaminohydrolases (DDAHs) expression, Nrf2 expression and PPAR-ɣ expression (P < 0.001, P < 0.003). These results suggest that CAP, TEL and BM pretreatment could reduce renal IR injury via anti-inflammatory, antioxidant and anti-apoptotic effects. © 2016 John Wiley & Sons Australia, Ltd.

  11. Roles of MgO release from polyethylene glycol 6000-based solid dispersions on microenvironmental pH, enhanced dissolution and reduced gastrointestinal damage of telmisartan.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Seung Aeon; Nho, Vo Hong; Chi, Sang-Cheol; Lee, Beom-Jin

    2011-05-01

    The roles of magnesium oxide (MgO) release from solid dispersions (SDs) in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and water were investigated to elucidate the enhanced dissolution and reduced intestinal damages of telmisartan as a model drug. The polyethylene glycol 6000 (PEG 6000) was used to prepare the SDs. Three SDs were prepared: SD1 (PEG, MgO, TEL), SD2 (PEG 6000, TEL), SD3 (MgO, TEL). The physical mixture (PM) consisting of SD2 and MgO was also prepared. A binary SD without MgO (SD2) was also prepared for comparison in microenvironmental pH (pH(M)) modulation. The faster MgO released, the less control of pH(M) and the less enhanced dissolution of TEL were in consequences. SD3 increased dissolution in SIF and water (about 67%). Interestingly, ternary SD1 showed almost complete dissolution in all three media but dissolution of PM was the lowest due to the fast release of MgO and poor modulation of pH(M). MgO did not change the drug crystallinity but did have a strong molecular interaction with the drug. Additionally, the SD3-bearing tablet quickly increased pH(M) but then gradually decreased due to faster release of MgO while the SD1-bearing tablet gradually increased pH(M) at all fractional dimensions of the tablet by the MgO slowly released. The pH(M) of PM-bearing tablets was not varied as a function of time. Thus, the MgO-bearing SD1 also minimized gastrointestinal tissue damage caused by the model drug.

  12. Regression of glomerular and tubulointerstitial injuries by dietary salt reduction with combination therapy of angiotensin II receptor blocker and calcium channel blocker in Dahl salt-sensitive rats.

    Directory of Open Access Journals (Sweden)

    Kazi Rafiq

    Full Text Available A growing body of evidence indicates that renal tissue injuries are reversible. We investigated whether dietary salt reduction with the combination therapy of angiotensin II type 1 receptor blocker (ARB plus calcium channel blocker (CCB reverses renal tissue injury in Dahl salt-sensitive (DSS hypertensive rats. DSS rats were fed a high-salt diet (HS; 4% NaCl for 4 weeks. Then, DSS rats were given one of the following for 10 weeks: HS diet; normal-salt diet (NS; 0.5% NaCl, NS + an ARB (olmesartan, 10 mg/kg/day, NS + a CCB (azelnidipine, 3 mg/kg/day, NS + olmesartan + azelnidipine or NS + hydralazine (50 mg/kg/day. Four weeks of treatment with HS diet induced hypertension, proteinuria, glomerular sclerosis and hypertrophy, glomerular podocyte injury, and tubulointerstitial fibrosis in DSS rats. A continued HS diet progressed hypertension, proteinuria and renal tissue injury, which was associated with inflammatory cell infiltration and increased proinflammatory cytokine mRNA levels, NADPH oxidase activity and NADPH oxidase-dependent superoxide production in the kidney. In contrast, switching to NS halted the progression of hypertension, renal glomerular and tubular injuries. Dietary salt reduction with ARB or with CCB treatment further reduced blood pressure and partially reversed renal tissues injury. Furthermore, dietary salt reduction with the combination of ARB plus CCB elicited a strong recovery from HS-induced renal tissue injury including the attenuation of inflammation and oxidative stress. These data support the hypothesis that dietary salt reduction with combination therapy of an ARB plus CCB restores glomerular and tubulointerstitial injury in DSS rats.

  13. Disconnection technique with a bronchial blocker for improving lung deflation: a comparison with a double-lumen tube and bronchial blocker without disconnection.

    Science.gov (United States)

    Yoo, Ji Young; Kim, Dae Hee; Choi, Ho; Kim, Kun; Chae, Yun Jeong; Park, Sung Yong

    2014-08-01

    One-lung ventilation (OLV) is accomplished with a double-lumen tube (DLT) or a bronchial blocker (BB). The authors compared the effectiveness of lung collapse using DLT, BB, and BB with the disconnection technique. Prospective, randomized, blind trial. A university hospital. Fifty-two patients undergoing elective pneumothorax surgery. Patients were assigned randomly to 1 of 3 groups: The DLT group (group 1), the BB group (group 2), and the BB with the disconnection technique group (group 3). The authors modified the disconnection technique in group 3 as follows: (1) turned off the ventilator and opened the adjustable pressure-limiting valve, allowing both lungs to collapse and (2) after loss of the CO2 trace on the capnograph, inflated the blocker cuff and turned on the ventilator, allowing only dependent-lung ventilation. Five and ten minutes after OLV, the degree of lung collapse was assessed by the surgeon, who was blinded to the isolation technique. The quality of lung collapse at 5 and 10 minutes was significantly better in groups 1 and 3 than in group 2. No significant differences were observed for the degree of lung collapse at any time point between groups 1 and 3. The average time for loss of the CO2 trace on the capnograph was 32.3±7.0 seconds in group 3. A BB with spontaneous collapse took longer to deflate and did not provide equivalent surgical exposure to the DLT. The disconnection technique could be helpful to accelerate lung collapse with a BB. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Long-term effects of beta-blocker use on lung function in Japanese patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Oda N

    2017-04-01

    Full Text Available Naohiro Oda,1 Nobuaki Miyahara,1,2 Hirohisa Ichikawa,3 Yasushi Tanimoto,4 Kazuhiro Kajimoto,5 Makoto Sakugawa,6 Haruyuki Kawai,7 Akihiko Taniguchi,1 Daisuke Morichika,1 Mitsune Tanimoto,1 Arihiko Kanehiro,1 Katsuyuki Kiura1 1Department of Allergy and Respiratory Medicine, Okayama University Hospital, 2Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama, 3Department of Respiratory Medicine, KKR Takamatsu Hospital, Takamatsu, 4Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center, Okayama, 5Department of Respiratory Medicine, Kobe Red Cross Hospital, Kobe, 6Department of Respiratory Medicine, Okayama Red Cross Hospital, 7Department of Respiratory Medicine, Okayama Saiseikai Hospital, Okayama, Japan Background: Some recent studies have suggested that beta-blocker use in patients with chronic obstructive pulmonary disease (COPD is associated with a reduction in the frequency of acute exacerbations. However, the long-term effects of beta-blocker use on lung function of COPD patients have hardly been evaluated. Patients and methods: We retrospectively reviewed 31 Japanese COPD patients taking beta-blockers for >1 year and 72 patients not taking them. The association between beta-blocker use and the annual change in forced expiratory volume in 1 second (FEV1 was assessed. Results: At baseline, patient demographic characteristics were as follows: 97 males (mean age 67.0±8.2 years; 32 current smokers; and Global Initiative for Chronic Obstructive Lung disease (GOLD stages I: n=26, II: n=52, III: n=19, and IV: n=6. Patients taking beta-blockers exhibited a significantly lower forced vital capacity (FVC, FEV1, and %FVC, and a more advanced GOLD stage. The mean duration of beta-blocker administration was 2.8±1.7 years. There were no differences in the annual change in FEV1 between patients who did and did not use beta-blockers (-7.6±93.5 mL/year vs -4.7±118.9 m

  15. Costs of tumor necrosis factor blockers per treated patient using real-world drug data in a managed care population.

    Science.gov (United States)

    Schabert, Vernon F; Watson, Crystal; Joseph, George J; Iversen, Paige; Burudpakdee, Chakkarin; Harrison, David J

    2013-10-01

    Several anti-inflammatory biologic medications are available in the United States for the treatment of moderate-to-severe rheumatoid arthritis, moderate-to-severe psoriasis, psoriatic arthritis, or ankylosing spondylitis. The tumor necrosis factor (TNF) blockers etanercept, adalimumab, and infliximab are approved for use in adults with any of these conditions, but predicting the annual costs of TNF-blocker treatment is complex due to differences in dosing schedules, treatment gaps, switching between TNF blockers, and dose escalation over time. To estimate the annual cost per treated patient from the payer perspective for etanercept, adalimumab, or infliximab in adults with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Adults in the IMS LifeLink Health Plan Claims Database were analyzed if they had at least 1 claim for etanercept, adalimumab, or infliximab between February 1, 2008, and July 5, 2010, and were continuously enrolled for at least 180 days before (pre-index period) through 360 days after the index claim (the first TNF-blocker claim after 6 months of continuous enrollment in the study period). Patients had a diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis, or a combination of these conditions, in the pre-index period. Cost was based on dose and price using April 2012 wholesale acquisition cost. Costs of administration were included for the first subcutaneous dose (etanercept or adalimumab) for new patients and for every intravenous dose (infliximab). Total TNF-blocker drug and administration costs, including nonindex TNF-blocker costs among patients who switched treatments, were divided by number of patients to yield cost per treated patient for each index TNF blocker. Subgroup analyses included cost by condition and cost for patients who were new to TNF-blocker treatment (no index TNF-blocker claim in the pre-index period) or continuing TNF-blocker treatment. Of the 30

  16. Old Friends With New Faces: Are Sodium Channel Blockers the Future of Adjunct Pain Medication Management?

    Science.gov (United States)

    Thomas, Ashley M; Atkinson, Timothy J

    2018-01-01

    Providers are being asked to decrease the emphasis and overutilization of long-term opioid therapy, but many are left without proper guidance on appropriate utilization of nonopioid therapies. Furthermore, therapeutic options are quite limited and many providers lack confidence in distinguishing available alternatives. When first-line therapy has failed in a patient, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy. To choose among alternative agents, an understanding of pharmacology, pharmacokinetics, and efficacy in targeting various pain conditions is necessary. This article focuses on the use of the carboxamide class of sodium channel blockers (carbamazepine, oxcarbazepine, eslicarbazepine) for adjunct pain medication management including research updates in pharmacology, pharmacokinetics, and current evidence for pain along with promising areas of research. It is an evidence update for clinical use of sodium channel blockers, clarifies misconceptions regarding their use, and highlights emerging research for improved pain targets that justifies additional study. We performed a complete review of the literature using the search terms, "oxcarbazepine," "carbamazepine," and "eslicarbazepine" in conjunction with "pharmacokinetics," "adverse effects," "pharmacology," "voltage-gated sodium channel subtype," "neuropathic pain," "inflammatory pain," "metabolism," "epoxide metabolite formation," "drug interactions," "CYP450 interactions," "pain phenotype," and "chronic pain management." Databases searched included PubMed and Google Scholar. Package inserts were used for drug structure illustration, adverse reactions, and bioavailability. Pharmacology and pharmacokinetic data were taken from randomized controlled trials evaluating this area as well as in vitro published results. For validity, only peer-reviewed literature was included. Evidence for sodium channel blockers in chronic pain management was limited. This review focuses

  17. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

    Science.gov (United States)

    Montoya, Alexa; Amaya, Clarissa N; Belmont, Andres; Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T; Aguilera, Renato J; Dickerson, Erin B; Torabi, Alireza; Dwivedi, Alok K; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A; Nahleh, Zeina

    2017-01-24

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

  18. Has beta-blocker use increased in patients with heart failure in internal medicine settings? Prognostic implications: RICA registry.

    Science.gov (United States)

    González-García, Andrés; Montero Pérez-Barquero, Manuel; Formiga, Francesc; González-Juanatey, José R; Quesada, M Angustias; Epelde, Francisco; Oropesa, Roberto; Díez-Manglano, Jesús; Cerqueiro, José M; Manzano, Luis

    2014-03-01

    Underuse of beta-blockers has been reported in elderly patients with heart failure. The aim of this study was to evaluate the current prescription of beta-blockers in the internal medicine setting, and its association with morbidity and mortality in heart failure patients. The information analyzed was obtained from a prospective cohort of patients hospitalized for heart failure (RICA registry] database, patients included from March 2008 to September 2011) with at least one year of follow-up. We investigated the percentage of patients prescribed beta-blockers at hospital discharge, and at 3 and 12 months, and the relationship of beta-blocker use with mortality and readmissions for heart failure. Patients with significant valve disease were excluded. A total of 515 patients were analyzed (53.5% women), with a mean age of 77.1 (8.7) years. Beta-blockers were prescribed in 62.1% of patients at discharge. A similar percentage was found at 3 months (65.6%) and 12 months (67.9%) after discharge. All-cause mortality and the composite of all-cause mortality and readmission for heart failure were significantly lower in patients treated with beta-blockers (hazard ratio=0.59, 95% confidence interval, 0.41-0.84 vs hazard ratio=0.64, 95% confidence interval, 0.49-0.83). This decrease in mortality was maintained after adjusting by age, sex, ejection fraction, functional class, comorbidities, and concomitant treatment. The findings of this study indicate that beta-blocker use is increasing in heart failure patients (mainly elderly) treated in the internal medicine setting, and suggest that the use of these drugs is associated with a reduction in clinical events. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  19. α-adrenergic blockers for the treatment of lower-urinary-tract symptoms and dysfunction in women.

    Science.gov (United States)

    Boyd, Katie; Hilas, Olga

    2014-06-01

    To evaluate the efficacy and safety of α-adrenergic blockers in the treatment of female lower-urinary-tract symptoms and dysfunction. Literature searches were conducted using EMBASE (1974 to January 2014), International Pharmaceutical Abstracts (1970 to January 2014), and MEDLINE (1946 to January 2014) to identify clinical trials evaluating the effects of α-adrenergic blockers in the treatment of women with lower-urinary-tract dysfunction. Bibliographies from relevant research articles were also reviewed for inclusion. All original research articles available in the English language were identified from the data sources. Primary literature evaluating outcomes related to urinary dysfunction and associated symptoms in women were included in this review. Articles describing the use of α-adrenergic blockers in other medical conditions or in men were excluded. A total of 15 clinical studies were identified and evaluated. Many studies showed an improvement in female lower-urinary-tract symptoms and dysfunction using α-adrenergic blockers. Most studies also reported adverse drug events of α-adrenergic blockers such as dizziness and hypotension. However, limitations of the studies conducted to date include small sample sizes, inconsistent study designs, and short duration of therapy. The role of α-adrenergic blockers in the treatment of urinary dysfunction and associated symptoms in women remains unclear. The majority of evidence suggests that these agents may have a place in therapy for female lower-urinary-tract symptoms and/or bladder outlet obstruction; however, data are conflicting. Clinicians should be aware of the potential clinical benefits but also recognize the potential adverse drug effects of α-adrenergic blockers.

  20. Comparative effects of sodium channel blockers in short term rat whole embryo culture

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, Mats F, E-mail: Mats.Nilsson@farmbio.uu.se [Department of Pharmaceutical Biosciences, Uppsala University (Sweden); Sköld, Anna-Carin; Ericson, Ann-Christin; Annas, Anita; Villar, Rodrigo Palma [AstraZeneca R and D Södertälje (Sweden); Cebers, Gvido [AstraZeneca R and D, iMed, 141 Portland Street, Cambridge, MA 02139 (United States); Hellmold, Heike; Gustafson, Anne-Lee [AstraZeneca R and D Södertälje (Sweden); Webster, William S [Department of Anatomy and Histology, University of Sydney (Australia)

    2013-10-15

    This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development.

  1. Detection of low-level DNA mutation by ARMS-blocker-Tm PCR.

    Science.gov (United States)

    Qu, Shoufang; Liu, Licheng; Gan, Shuzhen; Feng, Huahua; Zhao, Jingyin; Zhao, Jing; Liu, Qi; Gao, Shangxiang; Chen, Weijun; Wang, Mengzhao; Jiang, Yongqiang; Huang, Jie

    2016-02-01

    Low-level DNA mutations play important roles in cancer prognosis and treatment. However, most existing methods for the detection of low-level DNA mutations are insufficient for clinical applications because of the high background of wild-type DNA. In this study, a novel assay based on Tm-dependent inhibition of wild type template amplification was developed. The defining characteristic of this assay is an additional annealing step was introduced into the ARMS-blocker PCR. The temperature of this additional annealing step is equal to the Tm of the blocker. Due to this additional annealing step, the blocker can preferentially and specifically bind the wild-type DNA. Thus, the inhibition of wild type template is realized and the mutant DNA is enriched. The sensitivity of this assay was between 10(-4) and 10(-5), which is approximately 5 to 10 times greater than the sensitivity of the assay without the additional annealing step. To evaluate the performance of this assay in detecting K-ras mutation, we analyzed 100 formalin-fixed paraffin-embedded (FFPE) specimens from colorectal cancer patients using this new assay and Sanger sequencing. Of the clinical samples, 27 samples were positive for K-ras mutation by both methods. Our results indicated that this new assay is a highly selective, convenient, and economical method for detecting rare mutations in the presence of higher concentrations of wild-type DNA. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  2. Covered transjugular intrahepatic portosystemic shunt versus endoscopic therapy + β-blocker for prevention of variceal rebleeding.

    Science.gov (United States)

    Holster, I Lisanne; Tjwa, Eric T T L; Moelker, Adriaan; Wils, Alexandra; Hansen, Bettina E; Vermeijden, J Reinoud; Scholten, Pieter; van Hoek, Bart; Nicolai, Jan J; Kuipers, Ernst J; Pattynama, Peter M T; van Buuren, Henk R

    2016-02-01

    Gastroesophageal variceal bleeding in patients with cirrhosis is associated with significant morbidity and mortality, as well as a high rebleeding risk. Limited data are available on the role of transjugular intrahepatic portosystemic shunt (TIPS) with covered stents in patients receiving standard endoscopic, vasoactive, and antibiotic treatment. In this multicenter randomized trial, long-term endoscopic variceal ligation (EVL) or glue injection + β-blocker treatment was compared with TIPS placement in 72 patients with a first or second episode of gastric and/or esophageal variceal bleeding, after hemodynamic stabilization upon endoscopic, vasoactive, and antibiotic treatment. Randomization was stratified according to Child-Pugh score. Kaplan-Meier (event-free) survival estimates were used for the endpoints rebleeding, death, treatment failure, and hepatic encephalopathy. During a median follow-up of 23 months, 10 (29%) of 35 patients in the endoscopy + β-blocker group, as compared to 0 of 37 (0%) patients in the TIPS group, developed variceal rebleeding (P = 0.001). Mortality (TIPS 32% vs. endoscopy 26%; P = 0.418) and treatment failure (TIPS 38% vs. endoscopy 34%; P = 0.685) did not differ between groups. Early hepatic encephalopathy (within 1 year) was significantly more frequent in the TIPS group (35% vs. 14%; P = 0.035), but during long-term follow-up this difference diminished (38% vs. 23%; P = 0.121). In unselected patients with cirrhosis, who underwent successful endoscopic hemostasis for variceal bleeding, covered TIPS was superior to EVL + β-blocker for reduction of variceal rebleeding, but did not improve survival. TIPS was associated with higher rates of early hepatic encephalopathy. © 2015 by the American Association for the Study of Liver Diseases.

  3. Left Ventricular Remodeling after Myocardial Infarction: Characterization of a Swine Model on β-Blocker Therapy

    Science.gov (United States)

    Angeli, Franca S; Shapiro, Mia; Amabile, Nicolas; Orcino, Gina; Smith, Charles S; Tacy, Theresa; Boyle, Andrew J; Chatterjee, Kanu; Glantz, Stanton A; Grossman, William; Yeghiazarians, Yerem

    2009-01-01

    Current guidelines recommend β blockers for patients after myocardial infarction (MI). Novel therapies for heart failure should be tested in combination with this medication before entering clinical trials. In this methodologic study, we sought to describe the time course of systolic and diastolic parameters of cardiac performance over a 6-wk period in closed-chest model of swine MI treated with a β blocker. Myocardial infarction in pigs (n = 10) was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Echocardiography and pressure–volume data were collected before and at 1 and 6 wk after MI; histopathology was assessed at 6 wk. Left-ventricular (LV) volume increased significantly over 6 wk, with significant decreases in ejection fraction, wall motion index, stroke work, rate of pressure development (dP/dtmax), preload recruitable stroke work, and mechanical efficiency. Impairment of diastolic function was manifested by a significant increase in the exponential β coefficient of the LV end-diastolic pressure–volume relation and reduction of LV pressure decay. At 6 wk, histopathologic analysis showed that the size of the infarct area was 16.3% ± 4.4%, and the LV mass and myocyte cross-sectional area in both the infarct border and remote zones were increased compared with those of noninfarcted pigs (n = 5). These findings suggest a dynamic pattern of remodeling over time in a closed-chest ischemia–reperfusion swine model of acute MI on β-blocker therapy and may guide future studies. PMID:19619418

  4. Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, biophysical and physiological relevance.

    Science.gov (United States)

    Linsdell, Paul

    2014-02-26

    Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel causes cystic fibrosis, while inappropriate activity of this channel occurs in secretory diarrhea and polycystic kidney disease. Drugs that interact directly with CFTR are therefore of interest in the treatment of a number of disease states. This review focuses on one class of small molecules that interacts directly with CFTR, namely inhibitors that act by directly blocking chloride movement through the open channel pore. In theory such compounds could be of use in the treatment of diarrhea and polycystic kidney disease, however in practice all known substances acting by this mechanism to inhibit CFTR function lack either the potency or specificity for in vivo use. Nevertheless, this theoretical pharmacological usefulness set the scene for the development of more potent, specific CFTR inhibitors. Biophysically, open channel blockers have proven most useful as experimental probes of the structure and function of the CFTR chloride channel pore. Most importantly, the use of these blockers has been fundamental in developing a functional model of the pore that includes a wide inner vestibule that uses positively charged amino acid side chains to attract both permeant and blocking anions from the cell cytoplasm. CFTR channels are also subject to this kind of blocking action by endogenous anions present in the cell cytoplasm, and recently this blocking effect has been suggested to play a role in the physiological control of CFTR channel function, in particular as a novel mechanism linking CFTR function dynamically to the composition of epithelial cell secretions. It has also been suggested that future drugs could target this same pathway as a way of pharmacologically increasing CFTR activity in cystic fibrosis. Studying open channel blockers and their mechanisms of action has resulted in significant advances in our understanding of CFTR as a pharmacological target in disease

  5. Relationships of beta-blockers and anxiolytics intake and salivary secretion, masticatory performance and taste perception.

    Science.gov (United States)

    de Matos, Leandro Faria; Pereira, Stela Márcia; Kaminagakura, Estela; Marques, Leandro Silva; Pereira, Cássio Vicente; van der Bilt, Andries; Pereira, Luciano José

    2010-02-01

    Assess the influence of salivary flow on physiological parameters of the stomatognathic system in patients who take beta-blockers or anxiolytic medications. Sixty patients were divided into three groups based on the following criteria: Group 1, control (n=20; no use of medication); Group 2, use of antihypertensive beta-blockers (n=20); and Group 3, use of benzodiazepine anxiolytics (n=20). Salivary flow was assessed by determining stimulated and non-stimulated flow/minute. The quantification of the sense of taste was determined on a visual analogue scale (VAS) using solutions of 0.9% NaCl (salty), 50% sucrose (sweet), 20% unsweetened coffee (bitter) and 4.2% vinegar (sour). The DMFT index (number of decayed/missing/filled teeth) was determined by a calibrated examination, following the criteria of the World Health Organization (WHO). Masticatory performance was assessed with an Optosil comminution test and Rosim-Ramler equation. The results did not reveal a significant correlation between salivary flow and masticatory performance (p>0.05). We observed significant decreased non-stimulated salivary flow for Group 2 (p=0.05) when compared to controls. However, taste perception was not influenced by salivary secretion amongst groups. Furthermore, we observed a significant negative correlation between non-stimulated salivary flow and DMFT in Group 1 (p=0.02; r=-0.52). Patients under beta-blockers therapy presented reduced non-stimulated salivary flow when compared to controls, without influencing the sense of taste or masticatory performance. The use of anxiolytics did not affect salivary flow and taste perception in the studied sample. Copyright 2009 Elsevier Ltd. All rights reserved.

  6. Effects of prostatic inflammation on LUTS and alpha blocker treatment outcomes

    Directory of Open Access Journals (Sweden)

    Ha Na Lee

    2014-06-01

    Full Text Available Purpose To evaluate the association between prostatic inflammation and lower urinary tract symptoms (LUTS, and to identify the effects of prostatic inflammation on the treatment with an alpha blocker. Materials and Methods 111 Participants who were aged ≥ 50 years, the presence of LUTS (maximal flow rate < 20 m/s, IPSS ≥ 11, and an elevated PSA level (3-20ng/mL were treated with tamsulosin 0.2mg once daily for 3 months after prostate biopsies. Prostatic inflammation was scored as none (0, mild (I, moderate (II, or marked (III. LUTS parameters including urine flow rates, IPSS, PSA, and prostate volume were evaluated. Results Inflammation grading resulted in 25, 60, and 26 patients that were grade 0, I, and II, respectively. Lower grade inflammation was related to higher urine flow rate at baseline. Patients with higher inflammation grades had larger prostate volumes, larger total and transitional zone volumes, and higher PSA levels. Overall, urine flow rates and residual urine volume were improved after 3 months of alpha blocker therapy. Eighty percent of patients with grade 0 inflammation, 73% of patients with grade I inflammation, and 92.3% of patients with grade II inflammation showed improvement of LUTS after treatment. Longer duration of treatment was related to a decreased chance of improvement of LUTS. Patients with increased IPSS voiding subscales could be predictive of improvement of LUTS. Conclusions Patients with high grade inflammation had lower flow rates and higher prostatic volumes than patients with low grade inflammation. Inflammation grade did not affect the outcomes of alpha blocker treatment.

  7. Acrolein-mediated conduction loss is partially restored by K+ channel blockers

    Science.gov (United States)

    Yan, Rui; Page, Jessica C.

    2015-01-01

    Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K+ channels due to myelin damage leads to conduction block, and K+ channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K+ channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K+ channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases. PMID:26581866

  8. Calcium channel blockers in the management of hypertension in the elderly.

    Science.gov (United States)

    Caballero-Gonzalez, Francisco J

    2015-01-01

    The aging population is rapidly increasing, and is mainly due to medical advances and the control of chronic diseases, with a real worldwide increase in the elderly population. Special emphasis has been placed on the management of hypertension in the geriatric patient, since its long-term benefits have been shown to prevent both cerebral and cardiac infarctions. Calcium channel blockers have been shown to be effective in this condition in the elderly. Their success depends on their mechanism of action, as well as on the physiological changes observed, and on the aging process itself, which include cardiac hypertrophy, calcification of cardiac valves, and a decrease in the excitation-conduction system. There is thickening of the tunica intima of the arteries, and the production of nitric oxide at cellular level decreases with age, along with an increase in endothelin 1, which leads to vascular endothelium dysfunction. In the kidneys, there is a decrease in prostacyclin, endothelial hyperpolarization factor, as well as the Klotho anti-aging protein, which leads to an increase in blood pressure. Calcium channel blocker drugs have been shown to be effective in any age group for the management of hypertension, and are safe in the elderly patients. These drugs block L-type calcium channels, with the long-acting or latest generation dihydropyridines being the most effective of this group. Several studies, including SYST-EUR2, NORDIL, and STOP-2, have demonstrated the effectiveness of these drugs in the geriatric patient. The prescribing of long-acting calcium channel blocker drugs in a single dose is the most recommended. The safety in the use of this drug group has been demonstrated in the treatment of hypertension in the elderly patient, with a level of effectiveness similar to other widely used drugs.

  9. The β-blocker Nebivolol Is a GRK/β-arrestin biased agonist.

    Directory of Open Access Journals (Sweden)

    Catherine E Erickson

    Full Text Available Nebivolol, a third generation β-adrenoceptor (β-AR antagonist (β-blocker, causes vasodilation by inducing nitric oxide (NO production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the controversy regarding the pharmacological action of nebivolol. Carvedilol is another β-blocker that induces NO production. A prominent pharmacological mechanism of carvedilol is biased agonism that is independent of Gαs and involves G protein-coupled receptor kinase (GRK/β-arrestin signaling with downstream activation of the epidermal growth factor receptor (EGFR and extracellular signal-regulated kinase (ERK. Due to the pharmacological similarities between nebivolol and carvedilol, we hypothesized that nebivolol is also a GRK/β-arrestin biased agonist. We tested this hypothesis utilizing mouse embryonic fibroblasts (MEFs that solely express β2-ARs, and HL-1 cardiac myocytes that express β1- and β2-ARs and no detectable β3-ARs. We confirmed previous reports that nebivolol does not significantly alter cAMP levels and thus is not a classical agonist. Moreover, in both cell types, nebivolol induced rapid internalization of β-ARs indicating that nebivolol is also not a classical β-blocker. Furthermore, nebivolol treatment resulted in a time-dependent phosphorylation of ERK that was indistinguishable from carvedilol and similar in duration, but not amplitude, to isoproterenol. Nebivolol-mediated phosphorylation of ERK was sensitive to propranolol (non-selective β-AR-blocker, AG1478 (EGFR inhibitor, indicating that the signaling emanates from β-ARs and involves the EGFR. Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. Additionally, nebivolol induced redistribution of β-arrestin 2 from a diffuse staining pattern into more intense punctate spots. We conclude that nebivolol is a β2

  10. In Silico Predictions of hERG Channel Blockers in Drug Discovery

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Sørensen, Flemming Steen

    2011-01-01

    whereas QSAR and classification models provide a faster assessment and detection of hERG-related drug toxicity, limitation on the applicability domain of the current models and integration of data from diverse in vitro approaches are still issues to challenge.Therefore, this review will emphasize...... on current methods to predict hERG blockers and the need of consistent data to improve the quality and performance of the in silico models. Finally, integration of network-based analysis on drugs inducing potentially long-QT syndrome and arrhythmia will be discussed as a new perspective for a better...

  11. Alpha blocker prazosin for the treatment of benign prostatic hypertrophy (BPH.

    Directory of Open Access Journals (Sweden)

    Punekar S

    1995-10-01

    Full Text Available In this study medical treatment with alpha blocker-prazosin is compared with transurethral resection of prostate (TURP in 62 patients suffering from benign enlargement of prostate with a gland size of less than 20 gms. After thorough interrogation patients were offered either TURP or prazosin therapy. Symptom scoring, residual volume of urine and urinary flow rates were estimated in both the groups before and 3 months after the therapy. 23.5% patients in prazosin group while 90% of patients in TURP group had significant improvement. This distinctly brings out the superiority of TURP for benign enlargement of prostate.

  12. Non-selective beta-blockers may reduce risk of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Thiele, Maja; Albillos, Agustín; Abazi, Rozeta

    2015-01-01

    BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are used in patients with cirrhosis and oesophageal varices. Experimental data suggest that NSBB inhibit angiogenesis and reduce bacterial translocation, which may prevent hepatocellular carcinoma (HCC). We therefore assessed the effect of NSBB.......052 to -0.001; number needed to treat 38 patients). There was no heterogeneity (I(2) = 7%) or evidence of small study effects (Eggers P = 0.402). The result was not confirmed in sequential analysis, which suggested that 3719 patients were needed to achieve the required information size. NSBB did not reduce...

  13. Cardiac arrest after esmolol administration: a review of acute beta-blocker toxicity.

    Science.gov (United States)

    Litman, R S; Zerngast, B A

    1996-10-01

    An 11-year-old, 25-kg girl with congenital myelomeningocele was scheduled for posterior spinal fusion because of progressive scoliosis. After induction of general anesthesia and administration of a standard dose of intravenous esmolol hydrochloride, her cardiac rhythm progressed to asystole. Although given ephedrine, epinephrine, and atropine sulfate, the patient's normal heart rhythm could not be restored until calcium chloride was administered. A review of the medical literature indicates that the optimal treatment for acute beta-blocker toxicity is intravenous glucagon. Calcium administration should also be considered. Acute esmolol toxicity may be self-limiting because of its extremely short half-life.

  14. Are there any positive effects of TNF-alpha blockers on bone metabolism?

    Directory of Open Access Journals (Sweden)

    A. Sulli

    2011-09-01

    Full Text Available Secondary osteoporosis (OP is a well-recognized complication of rheumatoid arthritis (RA. Treatment with TNF-a blockers, might influence bone metabolism and prevent structural bone damage in RA, in particular at the periarticular regions. Objective: To assess the influence of anti-TNF-a therapy, on bone metabolism in RA patients. 36 RA patients were treated with stable therapy of prednisone (7.5 mg/day and methotrexate (MTX=10 mg/week. Nine of these RA patients further received etanercept (25 mg, twice/weekly and eleven infliximab (3mg/kg on 0, 2, 6, and every 8 weeks thereafter. A control group included 16 RA patients only with stable therapy (some dosage of prednisone and MTX. Quantitative Ultrasound (QUS bone densitometry was obtained at the metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS device (IGEA, Carpi, Italy. Bone mineral density (BMD of the hip and lumbar spine were performed with a densitometer ( Lunar Prodigy, GE, USA at baseline and after 12 months. Soluble bone turnover markers [osteocalcin (OC, bone alkaline phospatase (ALP deoxypyridinoline/creatinine ratio (Dpd/Cr and cross-linked N-telopeptide of type I collagen / creatinine ratio (NTx/Cr] were measured using ELISA tests. Results: AD-SoS values were found increased by +4.55% after 12 months of treatment in the RA patients treated with anti-TNF-a therapy. On the contrary, the Ad-SoS levels decreased by -4.48% during the same period in the control RA group. BMD increased by +3.64% at lumbar spine and +2.90% at the hip (both p<0.001 in TNF-a blockers-treated patients and decreased by -2.89% and -3.10% (both p<0.001, respectively at lumbar spine and at the hip in RA patients without anti-TNF-a therapy. In RA patients treated with TNF-a blockers, OC and bone ALP levels were found significantly increased (p<0.01 and Dpd/Cr or NTx/Cr levels were found significantly decreased (p<0.01 at 12 months when compared to baseline values. Conclusion: During 12

  15. Intraoperative Extracorporeal Carbon Dioxide Removal During Apneic Oxygenation with an EZ-Blocker in Tracheal Surgery.

    Science.gov (United States)

    Rispoli, Marco; Nespoli, Moana Rossella; Mattiacci, Dario Maria; Esposito, Marianna; Corcione, Antonio; Buono, Salvatore

    2016-06-01

    Tracheal surgery requires continued innovation to manage the anesthetic during an open airway phase. A common approach is apneic oxygenation with continuous oxygen flow, but the lack of effective ventilation causes hypercapnia, with respiratory acidosis. We used extracorporeal carbon dioxide removal for intraoperative decapneization during apneic oxygenation in a 64-year-old woman who was scheduled for tracheal surgery because of tracheal stenosis caused by long-term intubation. Our findings demonstrate that even after 40 minutes of total apnea, using an EZ-blocker for oxygenation and external decapneization, hemodynamic and gas exchange variables never demonstrated any dangerous alterations.

  16. Association of β-Blockers With Functional Outcomes, Death, and Rehospitalization in Older Nursing Home Residents After Acute Myocardial Infarction.

    Science.gov (United States)

    Steinman, Michael A; Zullo, Andrew R; Lee, Yoojin; Daiello, Lori A; Boscardin, W John; Dore, David D; Gan, Siqi; Fung, Kathy; Lee, Sei J; Komaiko, Kiya D R; Mor, Vincent

    2017-02-01

    Although β-blockers are a mainstay of treatment after acute myocardial infarction (AMI), these medications are commonly not prescribed for older nursing home residents after AMI, in part owing to concerns about potential functional harms and uncertainty of benefit. To study the association of β-blockers after AMI with functional decline, mortality, and rehospitalization among long-stay nursing home residents 65 years or older. This cohort study of nursing home residents with AMI from May 1, 2007, to March 31, 2010, used national data from the Minimum Data Set, version 2.0, and Medicare Parts A and D. Individuals with β-blocker use before AMI were excluded. Propensity score-based methods were used to compare outcomes in people who did vs did not initiate β-blocker therapy after AMI hospitalization. Functional decline, death, and rehospitalization in the first 90 days after AMI. Functional status was measured using the Morris scale of independence in activities of daily living. The initial cohort of 15 720 patients (11 140 women [70.9%] and 4580 men [29.1%]; mean [SD] age, 83 [8] years) included 8953 new β-blocker users and 6767 nonusers. The propensity-matched cohort included 5496 new users of β-blockers and an equal number of nonusers for a total cohort of 10 992 participants (7788 women [70.9%]; 3204 men [29.1%]; mean [SD] age, 84 [8] years). Users of β-blockers were more likely than nonusers to experience functional decline (odds ratio [OR], 1.14; 95% CI, 1.02-1.28), with a number needed to harm of 52 (95% CI, 32-141). Conversely, β-blocker users were less likely than nonusers to die (hazard ratio [HR], 0.74; 95% CI, 0.67-0.83) and had similar rates of rehospitalization (HR, 1.06; 95% CI, 0.98-1.14). Nursing home residents with moderate or severe cognitive impairment or severe functional dependency were particularly likely to experience functional decline from β-blockers (OR, 1.34; 95% CI, 1.11-1.61 and OR, 1.32; 95% CI, 1.10-1.59, respectively

  17. Impact of selective and nonselective beta-blockers on the risk of severe exacerbations in patients with COPD

    Directory of Open Access Journals (Sweden)

    Huang YL

    2017-10-01

    Full Text Available Yueh Lan Huang,1 Chih-Cheng Lai,2 Ya-Hui Wang,3 Cheng-Yi Wang,1 Jen-Yu Wang,1 Hao-Chien Wang,4 Chong-Jen Yu,4 Likwang Chen5 On behalf of the Taiwan Clinical Trial Consortium for Respiratory Diseases (TCORE 1Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, 2Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, 3Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, 4Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, 5Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan Background: There is conflicting information regarding the effects of selective and nonselective beta-blocker treatment in patients with COPD.Participants and methods: This nested case–control study used the Taiwan National Health Insurance Research Database. We included COPD patients who used inhalation steroid and beta-blockers between 1998 and 2010. From this cohort, there were 16,067 patients with severe exacerbations included in the analysis and 55,970 controls matched on age, sex, COPD diagnosis year, and beta-blockers treatment duration by risk set sampling.Results: For the selective beta-blocker users, the current users had a lower risk of severe exacerbations than the nonusers (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.85–0.96. In contrast, for the nonselective beta-blocker users, the current users had a higher risk of severe acute exacerbations than the nonusers (OR, 1.21; 95% CI, 1.14–1.27. A higher risk of severe exacerbation during increasing mean daily dose or within about the initial 300 days was found in nonselective beta-blockers, but not in selective beta-blockers. One selective beta-blocker, betaxolol, had a

  18. Improving documentation of a beta-blocker quality measure through an anesthesia information management system and real-time notification of documentation errors.

    Science.gov (United States)

    Nair, Bala G; Peterson, Gene N; Newman, Shu-Fang; Wu, Wei-Ying; Kolios-Morris, Vickie; Schwid, Howard A

    2012-06-01

    Continuation of perioperative beta-blockers for surgical patients who are receiving beta-blockers prior to arrival for surgery is an important quality measure (SCIP-Card-2). For this measure to be considered successful, name, date, and time of the perioperative beta-blocker must be documented. Alternately, if the beta-blocker is not given, the medical reason for not administering must be documented. Before the study was conducted, the institution lacked a highly reliable process to document the date and time of self-administration of beta-blockers prior to hospital admission. Because of this, compliance with the beta-blocker quality measure was poor (-65%). To improve this measure, the anesthesia care team was made responsible for documenting perioperative beta-blockade. Clear documentation guidelines were outlined, and an electronic Anesthesia Information Management System (AIMS) was configured to facilitate complete documentation of the beta-blocker quality measure. In addition, real-time electronic alerts were generated using Smart Anesthesia Messenger (SAM), an internally developed decision-support system, to notify users concerning incomplete beta-blocker documentation. Weekly compliance for perioperative beta-blocker documentation before the study was 65.8 +/- 16.6%, which served as the baseline value. When the anesthesia care team started documenting perioperative beta-blocker in AIMS, compliance was 60.5 +/- 8.6% (p = .677 as compared with baseline). Electronic alerts with SAM improved documentation compliance to 94.6 +/- 3.5% (p < .001 as compared with baseline). To achieve high compliance for the beta-blocker measure, it is essential to (1) clearly assign a medical team to perform beta-blocker documentation and (2) enhance features in the electronic medical systems to alert the user concerning incomplete documentation.

  19. Coronary computed tomography angiography - Tolerability of β-blockers and contrast media, and temporal changes in radiation dose

    DEFF Research Database (Denmark)

    Pedersen, Charlotte; Thomsen, Camilla F; Hosbond, Susanne Elisabeth

    2014-01-01

    Abstract Objective: To determine the risk of administration of β-blockers, contrast induced nephropathy (CIN) and trend in x-rays use, during coronary computed tomography angiography (CCTA). Methods: A total of 416 patients were referred for elective CCTA. To achieve a resting heart rate below 60.......0001. Conclusions: In terms of side effects to β-blockers and contrast media, there were no short term complications to CCTA. Furthermore the radiation dose was dramatically diminished over the last three years.......Abstract Objective: To determine the risk of administration of β-blockers, contrast induced nephropathy (CIN) and trend in x-rays use, during coronary computed tomography angiography (CCTA). Methods: A total of 416 patients were referred for elective CCTA. To achieve a resting heart rate below 60...... beats per minute oral and / or intravenously β-blockers were administered. Information was collected from patients on the adverse effects of β-blockers in the form of questionnaires. S-creatinine and estimated GFR (eGFR) were measured before and after contrast enhanced CCTA. Radiation exposure...

  20. Effects of beta-adrenergic blockers with different ancillary properties on lipid peroxidation in hyperthyroid rat cardiac muscle.

    Science.gov (United States)

    Asayama, K; Dobashi, K; Hayashibe, H; Kato, K

    1989-10-01

    To determine whether beta-blockade protects rat heart against thyroxine (T4)-induced accelelation of lipid peroxidation, in vivo effects of 3 beta-blockers with different ancillary properties on the mitochondrial oxidative enzyme, antioxidant enzymes and lipid peroxide were investigated. The rats were rendered hyperthyroid by adding T4 to their drinking water for 3 weeks and were treated simultaneously with either carteolol (a blocker with partial agonist activity; 30 mg/kg/day), atenolol (50 mg/kg/day) or arotinolol (a blocker with weak alpha-blocking action; 50 mg/kg/day). The T4-induced tachycardia was alleviated completely by either atenolol or arotinolol, but only partially by carteolol. Cytochrome c oxidase activity in the heart muscle was increased by T4 with a parallel increase in manganese (mitochondrial) superoxide dismutase. Atenolol, but neither carteolol nor arotinolol, suppressed this increase. Similarly, the T4-induced acceleration of lipid peroxidation was suppressed by atenolol alone. Glutathione peroxidase was markedly decreased, and both copper zinc (cytosolic) superoxide dismutase and catalase were also decreased or tended to be decreased by T4. The levels of these 3 enzymes were only minimally affected by the beta-blocker treatments. These results suggest that beta-blockade suppresses mitochondrial hypermetabolism and protects heart muscle against oxidative stress in hyperthyroidism, and that the ancillary properties of beta-blockers such as partial agonist activity and alpha-blocking action negate the protection.

  1. Angiotensin receptor-binding molecule in leukocytes in association with the systemic and leukocyte inflammatory profile.

    Science.gov (United States)

    Haruhara, Kotaro; Wakui, Hiromichi; Azushima, Kengo; Kurotaki, Daisuke; Kawase, Wataru; Uneda, Kazushi; Haku, Sona; Kobayashi, Ryu; Ohki, Kohji; Kinguchi, Sho; Ohsawa, Masato; Minegishi, Shintaro; Ishigami, Tomoaki; Matsuda, Miyuki; Yamashita, Akio; Nakajima, Hideaki; Tamura, Tomohiko; Tsuboi, Nobuo; Yokoo, Takashi; Tamura, Kouichi

    2018-02-01

    The components of the renin-angiotensin system in leukocytes is involved in the pathophysiology of non-communicable diseases (NCDs), including hypertension, atherosclerosis and chronic kidney disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) is an AT1R-specific binding protein, and is able to inhibit the pathological activation of AT1R signaling in certain animal models of NCDs. The aim of the present study was to investigate the expression and regulation of ATRAP in leukocytes. Human leukocyte ATRAP mRNA was measured with droplet digital polymerase chain reaction system, and analyzed in relation to the clinical variables. We also examined the leukocyte cytokines mRNA in bone-marrow ATRAP-deficient and wild-type chimeric mice after injection of low-dose lipopolysaccharide. The ATRAP mRNA was abundantly expressed in leukocytes, predominantly granulocytes and monocytes, of healthy subjects. In 86 outpatients with NCDs, leukocyte ATRAP mRNA levels correlated positively with granulocyte and monocyte counts and serum C-reactive protein levels. These positive relationships remained significant even after adjustment. Furthermore, the leukocyte ATRAP mRNA was significantly associated with the interleukin-1β, tumor necrosis factor-α and monocyte chemotactic protein-1 mRNA levels in leukocytes of NCDs patients. In addition, the leukocyte interleukin-1β mRNA level was significantly upregulated in bone marrow ATRAP-deficient chimeric mice in comparison to wild-type chimeric mice after injection of lipopolysaccharide. These results suggest that leukocyte ATRAP is an emerging marker capable of reflecting the systemic and leukocyte inflammatory profile, and plays a role as an anti-inflammatory factor in the pathophysiology of NCDs. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Use of angiotensin receptor – neprilysin inhibitors in heart failure: a ...

    African Journals Online (AJOL)

    with omapatrilat improves cardiac geometry and survival in cardiomyopathic hamsters more than does ACE inhibition with captopril. J Cardiovasc Pharmacol. 1999;34(6):78290. 24. Packer M, Califf RM, Konstam MA, Krum H, et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat ...

  3. ACE inhibition is superior to angiotensin receptor blockade for renography in renal artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Karanikas, Georgios; Becherer, Alexander; Wiesner, Karoline; Dudczak, Robert; Kletter, Kurt [Department of Nuclear Medicine, University of Vienna (Austria)

    2002-03-01

    Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much more sensitive than valsartan renography in detecting a clinically significant renal artery stenosis. Furthermore, our data suggest that other effects, such as that on the prostaglandin-bradykinin system, are of at least similar importance to ACE inhibition for the high diagnostic sensitivity of captopril renography regarding renovascular hypertension. (orig.)

  4. Combined Angiotensin Receptor Modulation in the Management of Cardio-Metabolic Disorders

    DEFF Research Database (Denmark)

    Paulis, Ludovit; Foulquier, Sébastien; Namsolleck, Pawel

    2016-01-01

    Cardiovascular and metabolic disorders, such as hypertension, insulin resistance, dyslipidemia or obesity are linked with chronic low-grade inflammation and dysregulation of the renin-angiotensin system (RAS). Consequently, RAS inhibition by ACE inhibitors or angiotensin AT1 receptor (AT1R...... blockade abolishes the AT1R-linked RAS almost completely with subsequent risk of hypotension and hypotension-related events, i.e. syncope or renal dysfunction. Such complications might be especially prominent in patients with renal impairment or patients with isolated systolic hypertension and normal...

  5. Predicting Kinase Activity in Angiotensin Receptor Phosphoproteomes Based on Sequence-Motifs and Interactions

    DEFF Research Database (Denmark)

    Bøgebo, Rikke; Horn, Heiko; Olsen, Jesper V

    2014-01-01

    Recent progress in the understanding of seven-transmembrane receptor (7TMR) signalling has promoted the development of a new generation of pathway selective ligands. The angiotensin II type I receptor (AT1aR) is one of the most studied 7TMRs with respect to selective activation of the β-arrestin ......Recent progress in the understanding of seven-transmembrane receptor (7TMR) signalling has promoted the development of a new generation of pathway selective ligands. The angiotensin II type I receptor (AT1aR) is one of the most studied 7TMRs with respect to selective activation of the β......-arrestin dependent signalling. Two complimentary global phosphoproteomics studies have analyzed the complex signalling induced by the AT1aR. Here we integrate the data sets from these studies and perform a joint analysis using a novel method for prediction of differential kinase activity from phosphoproteomics data....... The method builds upon NetworKIN, which applies sophisticated linear motif analysis in combination with contextual network modelling to predict kinase-substrate associations with high accuracy and sensitivity. These predictions form the basis for subsequently nonparametric statistical analysis to identify...

  6. Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial

    DEFF Research Database (Denmark)

    Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun

    2010-01-01

    -European countries: Norway, Sweden, Denmark, Belgium, Germany, Poland, Lithuania, Estonia and Finland. STUDY OUTCOMES: There are two co-primary effect variables: • Functional status at 6-months, measured by the modified Rankin Scale, and • vascular death, myocardial infarction or stroke during the first 6-months....... Secondary outcome variables: Secondary effect variables include • the Barthel index (functional status) • EuroQol (quality of life) and • Mini-mental state examination (cognition) at 6-months • Health economic costs during the first 6-months FUNDING: The Scandinavian Candesartan Acute Stroke Trial receives...

  7. Angiotensin receptors and angiotensin I-converting enzyme in rat intestine

    International Nuclear Information System (INIS)

    Duggan, K.A.; Mendelsohn, F.A.; Levens, N.R.

    1989-01-01

    The purpose of this study was to map the distribution of angiotensin II (ANG II) receptors and ANG I-converting enzyme (ACE) in rat intestine. ANG II binding sites were visualized by in vitro autoradiography using iodinated [Sar1, Ile8]ANG II. The distribution of ACE was mapped using an iodinated derivative of lisinopril. Male Sprague-Dawley rats were killed and the interior of the whole intestine washed with ice-cold saline. Segments of duodenum, jejunum, ileum, and colon were quickly frozen in a mixture of isopentane and dry ice. Twenty-micron frozen sections were thaw-mounted onto gelatin-coated slides, incubated with either ligand, and exposed to X-ray film. After exposure and subsequent development, the films were quantitated by computerized densitometry. ANG II receptors were most dense in the colon, followed by the ileum, duodenum, and jejunum. Within each segment of intestine, specific ANG II binding sites were localized exclusively to the muscularis. In contrast, ACE was present in both the mucosa and the muscularis. The colocalization of ANG II receptors and ACE may suggest a role for locally generated ANG II in the control of intestinal function. The luminal orientation of ACE in the mucosa of the small intestine may suggest that at this site ACE serves primarily to hydrolyze dietary peptides

  8. Estrogen effects on angiotensin receptors are modulated by pituitary in female rats

    International Nuclear Information System (INIS)

    Douglas, J.G.

    1987-01-01

    The present studies were designed to test the hypothesis that changes in angiotensin II (ANG II) receptors might modulate the layered target tissue responsiveness accompanying estradiol administration. Estradiol was infused continuously in oophorectomized female rats. Aldosterone was also infused in control and experimental animals to avoid estrogen-induced changes in renin and ANG II. ANG II binding constants were determined in radioreceptor assays. Estradiol increased binding site concentration in adrenal glomerulosa by 76% and decreased binding sites of uterine myometrium and glomeruli by 45 and 24%, respectively. There was an accompanying increase in the affinity of ANG II binding to adrenal glomerulosa and uterine myometrium. Because estrogen is a potent stimulus of prolactin release from the pituitary of rodents, studies were also designed to test the hypothesis that prolactin may mediate some or all of the estrogen-induced effects observed. Hypophysectomy abolished estradiol stimulation of prolactin release and most ANG II receptor changes. Prolactin administration to pituitary intact rats was associated with a 50% increase in receptor density of adrenal glomerulosa simulating estradiol administration. However, the changes in glomeruli and uterine myometrium were opposite in that both tissues also increased receptor density, suggesting that prolactin was not the sole mediator of the estrogen-induced receptor changes. In conclusion, regulation of ANG II receptors in a number of diverse target tissues by estradiol is complex with contributions from estrogens and pituitary factors, which include but do not exclusively involve prolactin

  9. Use of angiotensin receptor – neprilysin inhibitors in heart failure: a ...

    African Journals Online (AJOL)

    Heart failure is a clinical syndrome responsible for at least one-third of hospitalisations amongst cardiac patients, with escalating mortality and healthcare costs on both public and private health care. Both prevalence and incidence of heart failure increase steeply with advancing age, making it a growing public health ...

  10. [Progress in sodium channelopathies and biological functions of voltage-gated sodium channel blockers].

    Science.gov (United States)

    Wang, Hongyan; Gou, Meng; Xiao, Rong; Li, Qingwei

    2014-06-01

    Voltage-gated sodium channels (VGSCs), which are widely distributed in the excitable cells, are the primary mediators of electrical signal amplification and propagation. They play important roles in the excitative conduction of the neurons and cardiac muscle cells. The abnormalities of the structures and functions of VGSCs can change the excitability of the cells, resulting in a variety of diseases such as neuropathic pain, epilepsy and arrhythmia. At present, some voltage-gated sodium channel blockers are used for treating those diseases. In the recent years, several neurotoxins have been purified from the venom of the animals, which could inhibit the current of the voltage-gated sodium channels. Usually, these neurotoxins are compounds or small peptides that have been further designed and modified for targeted drugs of sodium channelopathies in the clinical treatment. In addition, a novel cysteine-rich secretory protein (CRBGP) has been isolated and purified from the buccal gland of the lampreys (Lampetra japonica), and it could inhibit the Na+ current of the hippocampus and dorsal root neurons for the first time. In the present study, the progress of the sodium channelopathies and the biological functions of voltage-gated sodium channel blockers are analyzed and summarized.

  11. Drug‐induced Raynaud's phenomenon: beyond β‐adrenoceptor blockers

    Science.gov (United States)

    Khouri, Charles; Blaise, Sophie; Carpentier, Patrick; Villier, Céline; Cracowski, Jean‐Luc

    2016-01-01

    Aim Drug‐induced Raynaud's phenomenon (RP) has long been associated with the use of different drugs, including cancer chemotherapy or β‐adrenoceptor blockers. However, sources report extremely variable prevalence and the level of evidence for each class is heterogeneous. Moreover, new signals are emerging from case reports and small series. Our objective was therefore to review available evidence about this adverse drug effect and to propose a mechanistic approach of drug‐induced RP. Methods A systematic review of English and French language articles was performed through Medline (1946–2015) and Embase (1974–2015). Further relevant papers were identified from the reference lists of retrieved articles. Results We identified 12 classes of drugs responsible for RP, with a variety of underlying mechanisms such as increased sympathetic activation, endothelial dysfunction, neurotoxicity or decreased red blood cell deformability. Cisplatin and bleomycin were associated with the highest risk, followed by β‐adrenoceptor blockers. Recent data suggest a possible involvement of tyrosine kinase inhibitors (TKI), through an unknown mechanism. Conclusion Drug‐induced RP is a probably underestimated adverse drug event, with limited available evidence regarding its prevalence. Although rare, serious complications like critical digital ischaemia have been reported. When these treatments are started in patients with a history of RP, careful monitoring must be made and, if possible, alternative therapies that do not alter peripheral blood flow should be considered. PMID:26949933

  12. [Treatment of arrhythmia in coronary patients and hypertensives with beta blockers and Depasan retard].

    Science.gov (United States)

    Kandziora, J

    1981-05-14

    In the ambulatory of an internal specialist a number of patients suffering from angina pectoris or hypertonia together with arrhythmic troubles received an initial treatment with beta-blockers over a period of 21 days. In cases in which arrhythmia persisted after this initial period the treatment was continued for another 21 days with the addition of Depasan retard in function of a second medicament. This combined treatment in form of an open study was extended to a total number of 50 patients presenting ventricular extrasystolia in 45 cases and in 5 cases absolute arrhythmia in addition to the main disease. Treatment with Depasan retard showed good or satisfactory results in 39 out of 45 patients suffering from ventricular extrasystoles, whilst no effect could be obtained in the 5 cases with absolute arrhythmia. No signs of incompatibility or unwanted interactions were observed in the course of this open study. Based on these results it can be concluded that Depasan retard should be recommended in those cases where on account of persistent arrhythmical troubles and especially extrasystoles, during a treatment with beta-blockers in patients suffering from angina pectoris or hypertonia, and additional treatment with anti-arrhythmical medicaments appears to be indicated.

  13. Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration-B mutant of Drosophila.

    Science.gov (United States)

    Sahly, I; Bar Nachum, S; Suss-Toby, E; Rom, A; Peretz, A; Kleiman, J; Byk, T; Selinger, Z; Minke, B

    1992-01-01

    Light accelerates degeneration of photoreceptor cells of the retinal degeneration B (rdgB) mutant of Drosophila. During early stages of degeneration, light stimuli evoke spikes from photoreceptors of the mutant fly; no spikes can be recorded from photoreceptors of the wild-type fly. Production of spike potentials from mutant photoreceptors was blocked by diltiazem, verapamil hydrochloride, and cadmium. Little, if any, effect of the (-)-cis isomer or (+)-cis isomer of diltiazem on the light response was seen. Further, the (+)-cis isomer was approximately 50 times more effective than the (-)-cis isomer in blocking the Ca2+ spikes, indicating that diltiazem action on the rdgB eye is mediated by means of blocking voltage-sensitive Ca2+ channels, rather than by blocking the light-sensitive channels. Application of the Ca(2+)-channel blockers (+)-cis-diltiazem and verapamil hydrochloride to the eyes of rdgB flies over a 7-day period largely inhibited light-dependent degeneration of the photoreceptor cells. Pulse labeling with [32P]phosphate showed much greater incorporation into eye proteins of [32P]phosphate in rdgB flies than in wild-type flies. Retarding the light-induced photoreceptor degeneration in the mutant by Ca(2+)-channel blockers, thus, suggests that toxic increase in intracellular Ca2+ by means of voltage-gated Ca2+ channels, possibly secondary to excessive phosphorylation, leads to photoreceptor degeneration in the rdgB mutant. Images PMID:1309615

  14. Use of Calcium Channel Blockers is Associated with Mortality in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Dominik G. Haider

    2015-12-01

    Full Text Available Background/Aims: The use of antihypertensive medicines has been shown to reduce proteinuria, morbidity, and mortality in patients with chronic kidney disease (CKD. A specific recommendation for a class of antihypertensive drugs is not available in this population, despite the pharmacodynamic differences. We have therefore analysed the association between antihypertensive medicines and survival of patients with chronic kidney disease. Methods: Out of 2687 consecutive patients undergoing kidney biopsy a cohort of 606 subjects with retrievable medical therapy was included into the analysis. Kidney function was assessed by glomerular filtration rate (GFR estimation at the time point of kidney biopsy. Main outcome variable was death. Results: Overall 114 (18.7% patients died. In univariate regression analysis the use of alpha-blockers and calcium channel antagonists, progression of disease, diabetes mellitus (DM type 1 and 2, arterial hypertension, coronary heart disease, peripheral vascular disease, male sex and age were associated with mortality (all pConclusion: The use of calcium channel blockers but not of other antihypertensive medicines is associated with mortality in primarily GN patients with CKD.

  15. Effects of telmisartan combined with nifedipine controlled release tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension

    Directory of Open Access Journals (Sweden)

    Feng Guo

    2017-10-01

    Full Text Available Objective: To investigate the effect of telmisartan combined with Nifedipine Controlled Release Tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension. Methods: A total of 92 cases of patients with coronary heart disease with mild to moderate hypertension were selected as the object of observation, according to the random data table, they were divided into the control group (n=46 and observation group (n=46, and patients in the control group were treated with Nifedipine Controlled Release Table therapy, on this basis, the observation group patients were given telmisartan treatment, two groups were treated for 6 months. The levels of the blood pressure, inflammatory factors, vascular endothelial function and left ventricular function compared between the two groups before and after treatment. Results: There were no significant differences in the levels of SBP, DBP, hs-CRP, TNF-α, NO, ET-1, LVEF, LVEDD and LVESD in the two groups before treatment. After treatment, two groups of SBP, DBP, hs-CRP, TNF-α, ET-1, LVEDD and LVESD levels were significantly lower than those in the same group before treatment, and after treatment, the levels of SBP, DBP, hs-CRP, TNF-α, ET-1 and LVESD in the observation group were significantly lower than those in the control group, while there were no significant difference in the level of LVEDD between the two groups after treatment; Compared with level in the group before treatment, the levels of NO and LVEF in the two groups were significantly increased, and the observation group [(82.13±19.01 µmol/L, (52.83±7.45%] was significantly higher than the control group [(67.37±13.08 µmol/L, (49.47±6.96%]. Conclusion: Telmisartan combined with Nifedipine Controlled Release Table in treating coronary heart disease with mild to moderate hypertension, can effectively control blood pressure, reduce the

  16. Treatment with oral beta-blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction

    DEFF Research Database (Denmark)

    Ersbøll, A S; Hedegaard, M; Søndergaard, L

    2014-01-01

    OBJECTIVE: To investigate the effect on fetal growth of treatment with oral beta-blockers during pregnancy in women with congenital or acquired heart disease. DESIGN: Historical matched cohort study. SETTING: Centre for Pregnant Women with Heart Disease, Copenhagen University Hospital, Denmark....... POPULATION: A cohort of 175 women with heart disease, grouped according to beta-blocker treatment, and a cohort of 627 women from the overall population matched on seven birthweight-determining factors. METHODS: Differences between groups were tested by simple descriptive statistics and assessed using......-blocker treatment was the only independent predictor of SGA, adjusting for several factors influencing fetal growth (the relative difference in expected birthweight was -12.2%; 95% CI -19.9 to -3.9%; P = 0.001). CONCLUSIONS: In a historical cohort of pregnancies complicated by maternal heart disease, treatment...

  17. Model tests of a once-through steam generator for land-blocker assessment and THEDA code verification. Final report

    International Nuclear Information System (INIS)

    Carter, H.R.; Childerson, M.T.; Moskal, T.E.

    1983-06-01

    The Babcock and Wilcox Company (B and W) operating Once-Through Steam Generators (OTSGs) have experienced leaking tubes in a region adjacent to the untubed inspection lane. The tube leaks have been attributed to an environmentally-assisted fatigue mechanism with moisture transported up the inspection lane being a major factor in the tube-failure process. B and W has developed a hardware modification (lane blockers) to mitigate the detrimental effects of inspection lane moisture. A 30-tube Laboratory Once-through Steam Generator (Designated OTSGC) was designed, fabricated, and tested. Tests were performed with and without five flat-plate lane blockers installed on tube-support plates (TSPs) 10, 11, 12, 13, and 14. The test results were utilized to determine the effectiveness of lane blockers for eliminating moisture transport to the upper tubesheet in the inspection lanes and to benchmark the predictive capabilities of a three-dimensional steam-generator computer code, THEDA

  18. Effect of beta-blocker therapy on functional status in patients with heart failure--a meta-analysis

    DEFF Research Database (Denmark)

    Abdulla, Jawdat; Køber, Lars; Christensen, Erik

    2005-01-01

    Association (NYHA) classification and exercise tolerance in chronic heart failure. METHODS AND RESULTS: We selected 28 RCTs evaluating beta-blocker versus placebo in addition to ACE inhibitor therapy. Combined results of 23 RCTs showed that beta-blockers improved NYHA class by at least one class with odds...... ratio (OR) 1.80 (1.33-2.43) poxygen uptake and 9 RCTs evaluating 6-min walk distance showed that beta-blockers had no significant effect...... compared with placebo, p=0.484, and p=0.730, respectively. Combined results of the 23 RCTs showed significant reducing effect on all cause mortality with OR=0.69 (0.59-0.82) ptherapy improves dyspnoea and prolongs exercise...

  19. T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers.

    Directory of Open Access Journals (Sweden)

    Wai-Ping Fung-Leung

    Full Text Available Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers.

  20. Beta-blockers and health-related quality of life in patients with peripheral arterial disease and COPD

    Directory of Open Access Journals (Sweden)

    Yvette RBM van Gestel

    2009-05-01

    Full Text Available Yvette RBM van Gestel1, Sanne E Hoeks1, Don D Sin2, Henk Stam3, Frans W Mertens3, Jeroen J Bax4, Ron T van Domburg5, Don Poldermans61Department of Anesthesiology, Erasmus Medical Center, Rotterdam, The Netherlands; 2Department of Medicine, University of British Columbia and The James Hogg iCAPTURe Center, St. Paul’s Hospital, Vancouver, Canada; 3Department of Pulmonology, Erasmus Medical Center, Rotterdam, The Netherlands; 4Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; 5Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands; 6Department of Vascular Surgery, Erasmus Medical Center, Rotterdam, The NetherlandsBackground: Beta-blockers are frequently withheld in patients with cardiovascular disease who also have chronic obstructive pulmonary disease (COPD because of concerns that they might provoke bronchospasm and cause deterioration in health status. Although beta1-selective beta-blockers are associated with reduced mortality in COPD patients, their effects on health status are unknown. The aim of this study was to investigate the relationship between beta-blockers and health-related quality of life (HRQOL in patients with peripheral arterial disease and COPD.Methods: Of the original cohort of 3371 vascular surgery patients, 1310 had COPD of whom 469 survived during long-term follow-up. These COPD patients were sent the Short Form-36 (SF-36 health-related quality of life questionnaire, which was completed and returned by 326 (70% patients.Results: No significant differences in any of the SF-36 domains were observed between COPD patients who did and did not use beta-blockers (p > 0.05 for all. Furthermore, beta-blockers were not associated with any impairment in HRQOL among patients with COPD.Conclusion: Beta-blockers had no material impact on the HRQOL of patients with peripheral arterial disease who also had COPD. This suggests that beta-blockers can, in most circumstances, be

  1. Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia

    DEFF Research Database (Denmark)

    Zakrzewska, Joanna M; Palmer, Joanne; Morisset, Valerie

    2017-01-01

    , can be administered at therapeutic doses without titration, and has shown good tolerability in healthy individuals in phase 1 studies. We therefore assessed the safety and efficacy of BIIB074 in patients with trigeminal neuralgia in a phase 2a study. METHODS: We did a double-blind, multicentre......BACKGROUND: Current standard of care for trigeminal neuralgia is treatment with the sodium channel blockers carbamazepine and oxcarbazepine, which although effective are associated with poor tolerability and the need for titration. BIIB074, a Nav1.7-selective, state-dependent sodium-channel blocker...

  2. Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic.

    Science.gov (United States)

    Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

    2018-01-01

    Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p  = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p  > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p  > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

  3. Adverse respiratory effect of acute β-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Morales, Daniel R; Jackson, Cathy; Lipworth, Brian J; Donnan, Peter T; Guthrie, Bruce

    2014-04-01

    β-Blockers are avoided in asthma over concerns regarding acute bronchoconstriction. Risk is greatest following acute exposure, including the potential for antagonism of β2-agonist rescue therapy. A systematic review of databases was performed to identify all randomized, blinded, placebo-controlled clinical trials evaluating acute β-blocker exposure in asthma. Effect estimates for changes in respiratory function, symptoms, and β2-agonist response were pooled using random effects meta-analysis with heterogeneity investigated. Acute selective β-blockers in the doses given caused a mean change in FEV1 of −6.9% (95% CI, −8.5 to −5.2), a fall in FEV1 of ≥20% in one in eight patients (P=.03), symptoms affecting one in 33 patients (P=.18), and attenuation of concomitant β2-agonist response of −10.2% (95% CI, −14.0 to −6.4). Corresponding values for acute nonselective β-blockers in the doses given were −10.2% (95% CI, −14.7 to −5.6), one in nine patients (P=.02), one in 13 patients (P=.14), and −20.0% (95% CI, −29.4 to −10.7). Following investigation of heterogeneity, clear differences were found for celiprolol and labetalol. A dose-response relationship was demonstrated for selective β-blockers. Selective β-blockers are better tolerated but not completely risk-free. Risk from acute exposure may be mitigated using the smallest dose possible and β-blockers with greater β1-selectivity. β-Blocker-induced bronchospasm responded partially to β2-agonists in the doses given with response blunted more by nonselective β-blockers than selective β-blockers. Use of β-blockers in asthma could possibly be based upon a risk assessment on an individual patient basis.

  4. TO STUDY OF ANTI-INFLAMMATORY EFFECT OF CALCIUM CHANNEL BLOCKERS IN RAT PAW EDEMA MODEL

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2016-02-01

    Full Text Available INTRODUCTION The process of inflammation is one of the most fundamental responses of the vascularised living tissue to local injury.1 Inflammation is a universal host defense process involving a complex network of cell-cell, cell-mediator & tissue interactions.2 AIM AND OBJECTIVES To study of anti-inflammatory effect of calcium channel blockers in rat paw edema model. MATERIALS AND METHODS To evaluate the anti-inflammatory effect with different doses of calcium channel blockers nifedipine, verapamil and standard drug ibuprofen in experimentally induced acute model of inflammation in male Wister rat. Inter drug comparison of anti-inflammatory efficacy of nifedipine, verapamil with standard drug ibuprofen in rats. Divide the animals into 3 groups each comprising at least six rats. Control group inject saline, standard group inject ibuprofen 20 mg/kg. test group inject (nifedipine & verapamil subcutaneously. After 30 min inject 0.1ml 1% (w/v Carrageenin in the plantar region of the left paw of all rats. The left hind paw was measured plethysmograph, immediately (zero hour and 4 hours after the sub plantar injection of Carrageenin. The difference between zero hour volume and the paw volume recorded at the end of 4 hrs. Indicated the actual volume. RESULT The statistical test ANOVA is applied to inter drug comparison. It is found that drug. Nifedipine 1mg/kg (86% has more efficacy significantly as compared to standard drug Ibuprofen 20mg/kg (55%, and drug Verapamil 1mg/kg (71% for its anti-inflammatory action. (F value is 94.27 >tab F 5.82 so this method is statistically highly significant. CONCLUSION Thus it was found that nifedipine has better anti-inflammatory efficacy as compared to ibuprofen, verapamil in various experimental anti-inflammatory models. The various experimental anti-inflammatory models were rat paw edema method. The calcium channel blockers included were nifedipine, verapamil and standard drug ibuprofen. Nifedipine has anti

  5. A comparative study to determine the clinical efficacy of Ramipril ...

    African Journals Online (AJOL)

    Inhibition of the renin-angiotensin system causes a reduction in urinary protein excretion. It is uncertain whether Angiotensin receptor blockers (ARBs) are equally effective antiproteinuric agents as Angiotensin converting Enzyme (ACE) inhibitors, or whether the combination of ACE inhibitors with ARBs is preferable to ACE ...

  6. Effects of Eprosartan on Diastolic Function and Neurohormones in Patients with Hypertension and Diastolic Dysfunction

    NARCIS (Netherlands)

    Voors, Adriaan A.; van de Wal, Ruud M.; Hartog, Jasper W. L.; Vijn, Richard G.; Hummel, Yoran M.; Plokker, Thijs W. M.; van Veldhuisen, Dirk J.; Jaarsma, Wybren

    To compare the effects of an angiotensin receptor blocker(ARB)-based regimen versus a non-ARB based regimen on diastolic function and neurohormones in patients with hypertension and diastolic dysfunction. 97 patients with a systolic blood pressure (SBP) a parts per thousand yen140 mmHg, a left

  7. The impact of age and gender on reporting of cough and angioedema with RAS inhibitors: A case/non-case in VigiBase

    NARCIS (Netherlands)

    Alharbi, Fawaz F.; Kholod, Anzhelika A.V.; Souverein, Patrick C.; Meyboom, Ron H.; de Groot, Mark; De Boer, Anthonius; Klungel, Olaf H.

    2016-01-01

    Background: Little is known about the effect of age and gender on reporting of cough/ angioedema with renin angiotensin system (RAS) inhibitors (angiotensin- converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and aliskiren, a direct renin inhibitor (DRI). Objectives: To assess

  8. Phenotype standardization of angioedema in the head and neck region caused by agents acting on the angiotensin system

    NARCIS (Netherlands)

    Wadelius, M.; Marshall, S. E.; Islander, G.; Nordang, L.; Karawajczyk, M.; Yue, Q.-Y.; Terreehorst, I.; Baranova, E. V.; Hugosson, S.; Sköldefors, K.; Pirmohamed, M.; Maitland-van der Zee, A.-H.; Alfirevic, A.; Hallberg, P.; Palmer, C. N. A.

    2014-01-01

    Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient

  9. Effect of candesartan treatment on left ventricular remodeling after aortic valve replacement for aortic stenosis

    DEFF Research Database (Denmark)

    Dahl, Jordi S; Videbaek, Lars; Poulsen, Mikael K

    2010-01-01

    In hypertension, angiotensin receptor blockers can augment regression of left ventricular (LV) hypertrophy. It is not known whether this also is the case after aortic valve replacement (AVR) for severe aortic stenosis (AS). To test the hypothesis that treatment with candesartan in addition...

  10. Irbesartan treatment does not influence plasma levels of the advanced glycation end products N(epsilon)(1-carboxymethyl)lysine and N(epsilon)(1-carboxyethyl)lysine in patients with type 2 diabetes and microalbuminuria. A randomized controlled trial

    DEFF Research Database (Denmark)

    Engelen, Lian; Persson, Frederik; Ferreira, Isabel

    2011-01-01

    BACKGROUND: In vitro and animal experiments have shown inhibiting effects of angiotensin receptor blockers (ARBs) on the formation of advanced glycation end products (AGEs), which are known to be involved in the development of cardiovascular complications in diabetes. However, sufficient human da...

  11. Therapeutic Approaches in Lowering Albuminuria : Travels Along the Renin-Angiotensin-Aldosterone-System Pathway

    NARCIS (Netherlands)

    Lambers Heerspink, Hiddo J.

    Achieving optimal blood pressure and albuminuria control is a major therapeutic treatment goal in patients with renal insufficiency. Angiotensin-converting enzyme-inhibitors (ACEIs) and angiotensin-receptor blockers (ARB) are the mainstay of therapy in these patients. However, despite these

  12. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials

    DEFF Research Database (Denmark)

    Bangalore, Sripal; Kumar, Sunil; Kjeldsen, Sverre E

    2011-01-01

    The risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs). We assessed the association between antihypertensive drugs and cancer risk in a comprehensive analysis of data from randomised clinical tr...

  13. Renin–angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis

    DEFF Research Database (Denmark)

    Bang, Casper N; Greve, Anders M; Køber, Lars

    2014-01-01

    BACKGROUND: Renin-angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild...

  14. Valsartan: the past, present and future

    DEFF Research Database (Denmark)

    Køber, Lars; Torp-Pedersen, Christian

    2005-01-01

    Valsartan (Diovan((R))) is a widely use angiotensin receptor blocker that prevents angiotensin II from binding to the subtype 1 receptor. Stimulation of the subtype 1 receptor is believed to mediate many of the deleterious effects accompanied by increased angiotensin II levels. Valsartan is effec...

  15. Albuminuria and blood pressure, independent targets for cardioprotective therapy in patients with diabetes and nephropathy

    DEFF Research Database (Denmark)

    Holtkamp, Frank A; de Zeeuw, Dick; de Graeff, Pieter A

    2011-01-01

    The long-term cardioprotective effect of angiotensin receptor blockers (ARBs) is associated with the short-term lowering of its primary target blood pressure, but also with the lowering of albuminuria. Since the individual blood pressure and albuminuria response to an ARB varies between and withi...

  16. Exposure to candesartan during the first trimester of pregnancy in type 1 diabetes: experience from the placebo-controlled diabetic retinopathy candesartan trials

    DEFF Research Database (Denmark)

    Porta, M; Hainer, J W; Jansson, S-O

    2011-01-01

    AIMS/HYPOTHESIS: The teratogenic consequences of angiotensin-converting enzyme inhibitors angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy are well described. However, the consequences of exposure during the first trimester are unclear, especially in diabet...

  17. Azilsartan Decreases Renal and Cardiovascular Injury in the Spontaneously Hypertensive Obese Rat

    Czech Academy of Sciences Publication Activity Database

    Khan, M. A. H.; Neckář, Jan; Cummens, B.; Wahl, G.M.; Imig, J. D.

    2014-01-01

    Roč. 28, č. 4 (2014), s. 313-322 ISSN 0920-3206 R&D Projects: GA ČR(CZ) GA13-10267S Institutional support: RVO:67985823 Keywords : angiotensin receptor blocker * kidney * metabolic syndrome * heart Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.189, year: 2014

  18. Development and validation of a high throughput LC–MS/MS method for simultaneous quantitation of pioglitazone and telmisartan in rat plasma and its application to a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Pinaki Sengupta

    2017-12-01

    Full Text Available Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence. Pioglitazone (PIO and telmisartan (TLM combination can be beneficial in effective control of cardiovascular complication in diabetes. In this research, we developed and validated a high throughput LC–MS/MS method for simultaneous quantitation of PIO and TLM in rat plasma. This developed method is more sensitive and can quantitate the analytes in relatively shorter period of time compared to the previously reported methods for their individual quantification. Moreover, till date, there is no bioanalytical method available to simultaneously quantitate PIO and TLM in a single run. The method was validated according to the USFDA guidelines for bioanalytical method validation. A linear response of the analytes was observed over the range of 0.005–10 µg/mL with satisfactory precision and accuracy. Accuracy at four quality control levels was within 94.27%–106.10%. The intra- and inter-day precision ranged from 2.32%–10.14 and 5.02%–8.12%, respectively. The method was reproducible and sensitive enough to quantitate PIO and TLM in rat plasma samples of a preclinical pharmacokinetic study. Due to the potential of PIO-TLM combination to be therapeutically explored, this method is expected to have significant usefulness in future. Keywords: LC–MS/MS, Rat plasma, Pharmacokinetic applicability, Telmisartan, Pioglitazone, Pharmacokinetic application

  19. Relationship between heart failure, concurrent chronic obstructive pulmonary disease and beta-blocker use

    DEFF Research Database (Denmark)

    Sessa, Maurizio; Mascolo, Annamaria; Mortensen, Rikke Nørmark

    2018-01-01

    Aims: To compare the hazard of all-cause, chronic obstructive pulmonary disease (COPD) and heart failure (HF) hospitalization in carvedilol vs. metoprolol/bisoprolol/nebivolol users with COPD and concurrent HF from 2009 to 2012, and to evaluate the use and persistence in treatment of these β......-blockers, their impact on the risk of COPD-related hospitalization, and the factors important for their selection. Methods and results: Cox and logistic regression were used for both unadjusted and adjusted analyses. Carvedilol users had a higher hazard of being hospitalized for HF compared with metoprolol...... persistence time than metoprolol/bisoprolol/nebivolol users. Patients exposed to carvedilol had an odds ratio (OR) of 1.38 (95% CI 1.23-1.56) for being hospitalized due to COPD within 60days after redeeming the first carvedilol prescription, which was similar to that observed in metoprolol...

  20. Beta-blocker subtype and risks of perioperative adverse events following non-cardiac surgery

    DEFF Research Database (Denmark)

    Jørgensen, Mads E.; Sanders, Robert D.; Køber, Lars

    2017-01-01

    performed a Danish Nationwide cohort study, 2005-2011, of patients treated chronically with beta blocker (atenolol, bisoprolol, carvedilol, metoprolol, propranolol, or other) prior to non-cardiac surgery. Risks of 30-day all-cause mortality (ACM) and 30-day major adverse cardiovascular events (MACE) were...... estimated using adjusted logistic regression models and odds ratios with 95% confidence intervals. We identified 61 660 patients, most frequently treated with metoprolol (67% of patients, mean age 69 years, 49% males), atenolol (10% of patients, mean age 68 years, 36% males), or carvedilol (9% of patients......, mean age 68 years, 60% males). The crude incidences of ACM and MACE were 4.1 and 3.5% in patients with metoprolol, 3.0 and 2.3% with atenolol, and 4.8 and 4.6% with carvedilol. In adjusted models, risks were not significantly different with atenolol (ACM; 1.10 [0.92-1.32], MACE; 1.08 [0...

  1. A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome.

    Science.gov (United States)

    Doyle, Jefferson J; Doyle, Alexander J; Wilson, Nicole K; Habashi, Jennifer P; Bedja, Djahida; Whitworth, Ryan E; Lindsay, Mark E; Schoenhoff, Florian; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Ehsan, Hamid; Huso, David; Thomas, Craig J; Caulfield, Mark J; Van Eyk, Jennifer E; Judge, Daniel P; Dietz, Harry C

    2015-10-27

    Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.

  2. The medieval physician Avicenna used an herbal calcium channel blocker, Taxus baccata L.

    Science.gov (United States)

    Tekol, Yalcin

    2007-07-01

    Calcium channel blockers are drugs which are important for current medical therapy. The first examples of synthetic congeners of this class of drugs appear around at the beginning of the 1960s. Review of the current and historical literature shows that Avicenna (Ibn Sina) (980-1037) had used the herbal drug 'Zarnab' (Taxus baccata L.) as a cardiac remedy. The leaves of T. baccata contain an alkaloid mixture (taxines). It was recently demonstrated that this drug possessed calcium channel blocking activity. So, it is evident that Avicenna used a drug with calcium channel blocking activity much earlier than the arrival of synthetic drugs belonging to the same pharmacological group. Copyright 2007 John Wiley & Sons, Ltd.

  3. Turbo Charge CPU Utilization in Fork/Join Using the ManagedBlocker

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    Fork/Join is a framework for parallelizing calculations using recursive decomposition, also called divide and conquer. These algorithms occasionally end up duplicating work, especially at the beginning of the run. We can reduce wasted CPU cycles by implementing a reserved caching scheme. Before a task starts its calculation, it tries to reserve an entry in the shared map. If it is successful, it immediately begins. If not, it blocks until the other thread has finished its calculation. Unfortunately this might result in a significant number of blocked threads, decreasing CPU utilization. In this talk we will demonstrate this issue and offer a solution in the form of the ManagedBlocker. Combined with the Fork/Join, it can keep parallelism at the desired level.

  4. Treatment with beta-blockers in nurse-led heart failure clinics

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Schou, Morten; Videbaek, Lars

    2007-01-01

    BACKGROUND: Beta-blockers (BBs) are a cornerstone in the treatment of chronic heart failure (HF), but several surveys have documented that many patients are not offered treatment or are not titrated to target doses. In part to address this problem, specialized, nurse-led HF clinics have been...... initiated in many countries. However, little information is available to describe if such programs are successful in initiating and up-titrating BBs in daily clinical practice. AIMS: To assess the proportion of patients with HF due to left ventricular systolic dysfunction on BB treatment three months after...... months (Ptitration continues to be a challenge even in specialized clinics dedicated to this task. Elderly patients appear to be less likely to receive treatment....

  5. Molecular Mechanism of Action and Selectivity of Sodium Ch annel Blocker Insecticides.

    Science.gov (United States)

    Silver, Kristopher; Dong, Ke; Zhorov, Boris S

    2017-01-01

    Sodium channel blocker insecticides (SCBIs) are a relatively new class of insecticides that are represented by two commercially registered compounds, indoxacarb and metaflumizone. SCBIs, like pyrethroids and DDT, target voltage-gated sodium channels (VGSCs) to intoxicate insects. In contrast to pyrethroids, however, SCBIs inhibit VGSCs at a distinct receptor site that overlaps those of therapeutic inhibitors of sodium channels, such as local anesthetics, anticonvulsants and antiarrhythmics. This review will recount the development of the SCBI insecticide class from its roots as chitin synthesis inhibitors, discuss the symptoms of poisoning and evidence supporting inhibition of VGSCs as their mechanism of action, describe the current model for SCBI-induced inhibition of VGSCs, present a model for the receptor for SCBIs on VGSCs, and highlight differences between data collected from mammalian and insect experimental models. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Abildstrom, Steen Z; Rasmussen, Jeppe N

    2005-01-01

    OBJECTIVES: To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. DESIGN: Information about patients with first AMI aged > or = 30 years and the dispensing of beta-blockers and ACE inhibitors from...

  7. Efficiency, efficacy, and safety of EZ-blocker compared with left-sided double-lumen tube for one-lung ventilation

    NARCIS (Netherlands)

    Mourisse, J.M.; Liesveld, J.; Verhagen, A.F.T.M.; Rooij, G. van; Heide, S. van der; Schuurbiers, O.C.J.; Heijden, E. van der

    2013-01-01

    BACKGROUND: Double-lumen tubes (DLTs) or bronchial blockers are commonly used for one-lung ventilation. DLTs are sometimes difficult or even impossible to introduce, and the incidence of postoperative hoarseness and airway injuries is higher. Bronchial blockers are more difficult to position and

  8. Utility of atropine in patients under beta-blocker effect during exercise stress echocardiography

    International Nuclear Information System (INIS)

    Munera, Ana G; Restrepo, Gustavo; Aristizabal, Dagnovar; Cubides, Carlos A

    2006-01-01

    The objective is to assess the usefulness of adding atropine 0.5 to 1.0 mg by intravenous injection during peak exercise in patients under beta-blocker effect that are subjected to exercise stress echocardiography. Population: exercise stress echocardiography was performed in 73 patients receiving beta-blocking agents with basal heart rate below 60 beats per minute (BPM). Two groups were established at random: group I (18 patients that did not receive atropine during maximal exercise) and group II (50 patients from whom 28 received 0.5 mg atropine IV 30 seconds to one minute before concluding the exercise and 22 patients who received 1.0 mg atropine IV 30 seconds to one minute before its conclusion). From a demographic point of view, there were no differences between the two groups. Mean age was 59 ± 10.8 years (57% male). Most of the patients received metoprolol (87%) and no significant statistical differences in relation with the doses were found in these two groups. At the end of the exercise, the patients had a mean heart rate of 84% from their maximal heart rate (MHR). The values post-exercise were 76% at 30 seconds, 68% at 60 sec., 62% at 90 sec., and 59% of the maximal heart rate at 120 sec. When comparing the percentage of the maximal heart rate achieved in maximal exercise and the one observed during the first 120 sec. after exercise, no statistically significant difference was observed between the two groups (p > 0.05). Conclusion: during the performance of stress exercise echocardiography, the administration of intravenous atropine was of no use for incrementing the peak heart rate post-exercise in patients with significant beta-blocker effect (basal heart rate < 60 BPM)

  9. Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory