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Sample records for receptor blocker abciximab

  1. In vitro effects of the glycoprotein IIb/IIIa receptor antagonists abciximab and eptifibatide on platelet aggregation in healthy cats.

    Science.gov (United States)

    Magee, Aliya N; Hogan, Daniel F; Sederquist, Kimberly A; Durham, Jaylyn A

    2014-03-01

    To determine effects of the glycoprotein IIb/IIIa receptor antagonists abciximab and eptifibatide on in vitro inhibition of cat platelets. Venous blood samples from 10 healthy cats. Blood samples were anticoagulated with hirudin. Aliquots of whole blood from each cat were allocated to 5 treatments (baseline, 50 μg of abciximab/mL, abciximab volumetric control treatment, 4 μM eptifibatide, and eptifibatide volumetric control treatment). Impedance platelet aggregometry was performed with 6.5 μM ADP or 32 μM thrombin receptor activator peptide (TRAP). Magnitude of platelet aggregation was determined by measuring the area under the curve 15 minutes after addition of ADP or TRAP. Eptifibatide caused a significant reduction in platelet aggregation, compared with baseline values, for aggregometry with both ADP (median, 50.0; range, 8 to 122 [baseline median, 306.0; baseline range, 130 to 664]) and TRAP (median, 75.5; range, 3 to 148 [baseline median, 219.0; baseline range, 97 to 578]). There was no significant difference in platelet aggregation with abciximab, the abciximab volumetric control treatment, or the eptifibatide volumetric control treatment for aggregometry with ADP or TRAP. Eptifibatide caused a significant reduction in platelet aggregation in vitro, but there was no identifiable antiplatelet effect for abciximab. Eptifibatide and abciximab have different binding and inhibitory actions; therefore, it can be hypothesized that abciximab would be ineffective in cats because of a lack of receptor binding, reduced binding kinetics, or lack of downstream signaling. Eptifibatide may be useful in identifying hyperreactive platelets in cats in an in vitro platelet inhibitory assay.

  2. Standard versus low-dose weight-adjusted heparin in patients treated with the platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3 Fab) during percutaneous coronary revascularization. PROLOG Investigators.

    Science.gov (United States)

    Lincoff, A M; Tcheng, J E; Califf, R M; Bass, T; Popma, J J; Teirstein, P S; Kleiman, N S; Hattel, L J; Anderson, H V; Ferguson, J J; Cabot, C F; Anderson, K M; Berdan, L G; Musco, M H; Weisman, H F; Topol, E J

    1997-02-01

    Blockade of the platelet glycoprotein IIb/IIIa receptor by abciximab (c7E3 Fab) during coronary intervention reduces the incidence of ischemic complications, but has been associated with a doubling of the risk for bleeding complications. The present pilot study investigated whether modification of heparin dosing and/or early sheath removal would reduce the hemorrhagic complications associated with abciximab. One hundred three patients undergoing coronary intervention received abciximab (0.25 mg/kg bolus, 10 microg/min infusion for 12 hours) and aspirin and were randomized by a 2 x 2 factorial design to 1 of 2 weight-adjusted heparin doses and to 1 of 2 strategies for heparin discontinuation and vascular sheath removal. In the "standard-dose heparin" group, an initial bolus of 100 U/kg was administered to achieve a procedural activated clotting time (ACT) > or = 300 seconds; in the "low-dose heparin" group, an initial bolus of 70 U/kg was administered without adjustment for ACT. In the "late sheath removal" arm, heparin infusion was continued for the 12-hour duration of abciximab infusion, followed by sheath removal; in the "early sheath removal" group, heparin was stopped after the interventional procedure and sheaths were removed during the abciximab infusion. There were no apparent differences between patients randomized to the different treatment groups with regard to the occurrence of ischemic end points. Rates of bleeding and blood transfusion were reduced by low-dose heparin and early sheath removal and were lowest when both strategies were combined. Reduction and weight adjustment of heparin dose and early sheath removal in the setting of platelet inhibition with abciximab during coronary intervention may be useful in diminishing the incidence of hemorrhagic complications without loss of clinical efficacy.

  3. 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

  4. Peripherally restricted CB1 receptor blockers.

    Science.gov (United States)

    Chorvat, Robert J

    2013-09-01

    Antagonists (inverse agonists) of the cannabinoid-1 (CB1) receptor showed promise as new therapies for controlling obesity and related metabolic function/liver disease. These agents, representing diverse chemical series, shared the property of brain penetration due to the initial belief that therapeutic benefit was mainly based on brain receptor interaction. However, undesirable CNS-based side effects of the only marketed agent in this class, rimonabant, led to its removal, and termination of the development of other clinical candidates soon followed. Re-evaluation of this approach has focused on neutral or peripherally restricted (PR) antagonists. Supporting these strategies, pharmacological evidence indicates most if not all of the properties of globally acting agents may be captured by molecules with little brain presence. Methodology that can be used to eliminate BBB penetration and the means (in vitro assays, tissue distribution and receptor occupancy determinations, behavioral paradigms) to identify potential agents with little brain presence is discussed. Focus will be on the pharmacology supporting the contention that reported agents are truly peripherally restricted. Notable examples of these types of compounds are: TM38837 (structure not disclosed); AM6545 (8); JD5037 (15b); RTI-12 (19). Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Abciximab: a reappraisal of its use in coronary care

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    Marco Valgimigli

    2008-03-01

    Full Text Available Marco Valgimigli, Gianluca Campo, Matteo Tebaldi, Roberto Carletti, Chiara Arcozzi, Roberto Ferrari, Gianfranco PercocoCardiovascular Institute, Azienda Ospedaliera Universitaria S. Anna, Ferrara, Italy and Cardiovascular Research Centre, Salvatore Maugeri Foundation, IRCCS Gussago (BS, ItalyAbstract: Platelet reactivity plays a pivotal role in the pathogenesis of ischemic adverse events during and after acute coronary syndromes (ACS, and percutaneous coronary intervention (PCI. Glycoprotein (GP IIb/IIIa inhibitors are the strongest antiplatelet agents currently available on the market and three different compounds, namely abciximab, tirofiban, and eptifibatide, have been approved for clinical use. Abciximab has been investigated in the clinical field far more extensively than the other GPIIb/IIIa inhibitors. Abciximab is an anti-integrin Fab fragment of a human – mouse chimeric monoclonal antibody with high affinity and a slow dissociation rate from the GP IIb/IIIa platelet receptor. Abciximab, given shortly before the coronary intervention, is superior to placebo in reducing the acute risk of ischemic complications (EPIC, EPISTENT, EPILOG trials; moreover, in the ISAR-REACT 2 study abciximab has been shown to reduce the risk of adverse events in patients with non ST-segment elevation ACS who are undergoing PCI even after optimal pre-treatment with 600 mg of clopidogrel. Finally, abciximab has been also used in abciximab-coated stent, with only bolus administration regimen and for direct intracoronary use with promising results that may extend and/or modify its current use in clinical practice in future.Keywords: abciximab, percutaneous coronary intervention, myocardial infarction

  6. 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

  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. The use of New Generation H1 Receptor Blockers and Advantages in Terms of Reliability

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    Muhammed Yayla

    2013-10-01

    Full Text Available H1 receptor blockers are one of the most commonly prescribed medications in the treatment of allergic disorders. These disease have reduced life quality of people and prevalent in the world. H1 receptor blockers has been used since 1940 and lead to some adverse effects such as sedation because of their chemical and pharmacological properties. Therefore new generations have been studied for reduced their adverse effect. The aims of this review are to exhibit advantages of new produced H1 receptor blockers compared to classical antihistamines and demonstrate efficacies of clinical uses of new produced H1 antihistamines. New generation H1 receptor blockers which have been developed after 1980s has less lipophilic properties and their sedative effects are minimized compared to classical antihistamines. Also, their specificity, affinity for H1 receptors and antihistaminergic effects are higher than classical H1 receptor blockers. Although new generation H1 receptor blockers are better tolerated than classical H1 receptor blockers, some of them lead to potential cardio toxicity. Consequently new generation H1 receptor blockers are reliable and efficient drugs, they provide convenience in the treatment of allergic disorders and prevent development of phobia against drugs.

  9. 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 (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 lever, 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

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

    DEFF Research Database (Denmark)

    Pena, Michelle J; Heinzel, Andreas; Rossing, Peter

    2016-01-01

    BACKGROUND: 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...

  13. 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

  14. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis

    National Research Council Canada - National Science Library

    Healey, Jeff S; Baranchuk, Adrian; Crystal, Eugene; Morillo, Carlos A; Garfinkle, Michael; Yusuf, Salim; Connolly, Stuart J

    2005-01-01

    This study was designed to identify all randomized clinical trial data evaluating angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for the prevention of atrial fibrillation (AF...

  15. Increased infections with β-blocker use in ischemic stroke, a β2-receptor mediated process?

    Science.gov (United States)

    Starr, Jordan B; Tirschwell, David L; Becker, Kyra J

    2017-06-01

    Strokes promote immunosuppression, partially from increased sympathetic activity. Altering sympathetic drive with β-blockers has variably been shown to improve stroke outcomes. This study adds to this literature using propensity score matching to limit confounding and by examining the effects of selective and non-selective β-blockers. Prospective data from acute ischemic stroke admissions at a single center from July 2010-June 2015 were analyzed. Outcomes included infection (urinary tract infection [UTI], pneumonia, or bacteremia), discharge modified Rankin Score (mRS), and in-hospital death. Any selective and non-selective β-blocker use during the first 3 days of admission were investigated with propensity score matching. A sensitivity analysis was also performed. This study included 1431 admissions. Any β-blocker use was associated with increased infections (16.4 vs. 10.7%, p = 0.030). Non-selective β-blocker use was associated with increased infections (18.9 vs. 9.7%, p = 0.005) and UTIs (13.0 vs. 5.5%, p = 0.009). Selective β-blocker use was not associated with infection. There were no associations between β-blocker use and in-hospital death or discharge mRS. In the sensitivity analysis, the association between non-selective β-blocker use and urinary tract infections persisted (12.5 vs. 4.2%, p = 0.044). No associations with death or mRS were found. Early β-blocker use after ischemic stroke may increase the risk of infection but did not change disability or mortality risk. The mechanism may be mediated by β2-adrenergic receptor antagonism given the different effects seen with selective versus non-selective β-blocker use.

  16. Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Axelsson, Anna; Iversen, Kasper; Vejlstrup, Niels

    2015-01-01

    . Treatment was well tolerated by patients with left ventricular outflow obstruction at baseline. INTERPRETATION: Our findings challenge the generally held view that angiotensin II receptor blockers reduce cardiac hypertrophy. Treatment with losartan was safe, suggesting that it can be used for other......BACKGROUND: No medical treatment has been reliably shown to halt or reverse disease progression in hypertrophic cardiomyopathy, but the results of several pilot studies have suggested beneficial effects of angiotensin II receptor blockers on left ventricular hypertrophy and fibrosis, which...... are predictive of an adverse outcome. We aimed to assess the effect of the angiotensin II receptor blocker losartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, adult patients (aged...

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

    Science.gov (United States)

    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.

  18. Histamine-2 receptor blockers alter the fecal microbiota in premature infants.

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    Gupta, Raegan W; Tran, Lynn; Norori, Johana; Ferris, Michael J; Eren, A Murat; Taylor, Christopher M; Dowd, Scot E; Penn, Duna

    2013-04-01

    Bacterial colonization is considered a major risk factor for necrotizing enterocolitis (NEC). The objective of the present study was to test the hypothesis that histamine-2 receptor (H2-) blockers alter colonic bacterial colonization by analyzing and comparing the fecal microbiota in premature infants with and without H2-blocker therapy using sensitive molecular biological techniques. Seventy-six premature infants ≤1500 g or Stool samples were collected from 25 infants receiving H2-blockers and 51 babies who had never received them. Following DNA extraction and PCR amplification of 16S rRNA, 454 pyrosequencing was undertaken and the resulting sequences were subjected to comparison with published sequence libraries. Proteobacteria and Firmicutes were the major phyla contributing to fecal microbial communities. Microbial diversity was lower, relative abundance of Proteobacteria (primarily of the family Enterobacteriaceae) was increased, whereas that of Firmicutes was decreased in the stools of infants receiving H2-blockers compared with those who had never received them. Although not designed to look specifically at the effect of H2-blockers on the incidence of NEC, our study suggests that their use lowers fecal microbial diversity and shifts the microfloral pattern toward Proteobacteria. These alterations in fecal microbiota may predispose the vulnerable immature gut to necrotizing enterocolitis and suggest prudence in the use of H2-blockers in the premature infant.

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

    NARCIS (Netherlands)

    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

    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

  20. 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.

  1. Uptake of angiotensin II receptor blockers in the treatment of hypertension

    NARCIS (Netherlands)

    Greving, JP; Denig, P; van der Veen, WJ; Beltman, FW; Sturkenboom, MCJM; de Zeeuw, D; Haaijer-Ruskamp, FM

    Objective: To examine trends in prescribing of angiotensin II receptor blockers (ARBs) as initial and second-line treatment of hypertension. Methods: We performed a cohort study in the Integrated Primary Care Information database, a general practice research database in The Netherlands. We included

  2. 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...

  3. 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...

  4. POSSIBILITY OF ANGIOTENSIN RECEPTOR BLOCKERS IN OPTIMIZING OF ANTIHYPERTENSIVE PHARMACOTHERAPY IN PATIENTS AFTER STROK

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    Z M. Sizova

    2013-01-01

    Full Text Available Current possibilities of AT1 receptor blockers (ARBs, such as candesartan, for optimization of antihypertensive therapy in stroke patients are presented in the article. ARBs are original drugs that effect to the delicate balance of pressor and depressor neurohormonal systems. They also have cerebroprotective action and are the drugs of choice for primary and secondary prevention of stroke in hypertensive patients

  5. Functional antagonism of different angiotensin II type I receptor blockers in human arteries

    NARCIS (Netherlands)

    Voors, AA; Buikema, H; van Buiten, A; Lubeck, RH; Boonstra, PW; van Veldhuisen, DJ; van Gilst, WH

    Objectives. To evaluate and compare the functional type and the degree of antagonism of the selective angiotensin II type I receptor blockers (ARB) losartan, EXP 3174 (the active metabolite of losartan), valsartan and candesartan in human internal mammary arteries. Methods. Human internal mammary

  6. Role of angiotensin receptor blockers in patients with left ventricular dysfunction : lessons from CHARM and VALIANT

    NARCIS (Netherlands)

    Voors, AA; van Veldhuisen, DJ

    2004-01-01

    The role of angiotensin receptor blockers (ARBs) in patients with left ventricular dysfunction has changed after the VALIANT and CHARM trials. CHARM proved that candesartan is a good alternative for patients with chronic heart failure who cannot tolerate ACE-inhibitors. Moreover, VALIANT

  7. 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.

  8. New basic science initiatives with the angiotensin II receptor blocker valsartan

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    Marc de Gasparo

    2000-06-01

    Full Text Available Summary Angiotensin II (Ang II plays a key role in the regulation of blood pressure and fluid homeostasis. Valsartan is a highly selective Ang II receptor blocker that specifically and selectively blocks Ang II at the AT1-receptor. In animal models, valsartan has shown positive effects on vasoconstriction, proliferation, remodelling, endothelial function and thrombogenesis, inflammation and atherosclerosis. These data are likely to be confirmed by the results of current clinical trials and valsartan is set to provide improved cardiovascular therapy in the future.

  9. Etanercept - TNF receptor and IgG1 Fc fusion protein: is it different from other TNF blockers?

    Science.gov (United States)

    Marotte, Hubert; Cimaz, Rolando

    2014-05-01

    TNF blockers have been available to treat various inflammatory disorders since more than a decade. T cells and macrophages mainly express TNF and activate many cells through two types of receptors. Pharmaceutical companies developed two types of TNF blockers: soluble receptors and monoclonal antibodies. Understanding of differences of structure and function can explain divergence of efficacy or side effects. Etanercept has the best retention rate in rheumatic diseases, but is less or not effective in granulomatous diseases, such as inflammatory bowel diseases or uveitis. However, etanercept induces less tuberculosis infections than anti-TNF blocker monoclonal antibodies.

  10. Abciximab for thrombolysis during intracranial aneurysm coiling

    Energy Technology Data Exchange (ETDEWEB)

    Gralla, Jan [West Wing, John Radcliffe Hospital, Department of Neuroradiology, Oxford (United Kingdom); Inselspital-University of Bern, Department of Neuroradiology, Bern (Switzerland); Rennie, Adam T.M.; Corkill, Rufus A.; Lalloo, Shivendra T.; Molyneux, Andrew; Byrne, James V.; Kuker, Wilhem [West Wing, John Radcliffe Hospital, Department of Neuroradiology, Oxford (United Kingdom)

    2008-12-15

    Thrombotic events are a common and severe complication of endovascular aneurysm treatment with significant impact on patients' outcome. This study evaluates risk factors for thrombus formation and assesses the efficacy and safety of abciximab for clot dissolution. All patients treated with abciximab during (41 patients) or shortly after (22 patients) intracranial aneurysm coil embolisation were retrieved from the institutional database (2000 to 2007, 1,250 patients). Sixty-three patients (mean age, 55.3 years, {+-}12.8) had received either intra-arterial or intravenous abciximab. Risk factors for clot formation were assessed and the angiographic and clinical outcome evaluated. No aneurysm rupture occurred during or after abciximab application. The intra-procedural rate of total recanalisation was 68.3%. Thromboembolic complications were frequently found in aneurysms of the Acom complex and of the basilar artery, whilst internal carotid artery aneurysms were underrepresented. Two patients died of treatment-related intracranial haemorrhages into preexisting cerebral infarcts. Two patients developed a symptomatic groin haematoma. Abciximab is efficacious and safe for thrombolysis during and after endovascular intracranial aneurysm treatment in the absence of preexisting ischaemic stroke. (orig.)

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Cernes, Relu; Mashavi, Margarita; Zimlichman, Reuven

    2011-01-01

    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.

  13. Long-term mortality after bolus-only administration of abciximab, eptifibatide, or tirofiban during percutaneous coronary intervention.

    Science.gov (United States)

    Marmur, Jonathan D; Poludasu, Shyam; Lazar, Jason; Cavusoglu, Erdal

    2009-02-01

    To evaluate the long-term mortality after bolus-only administration of abciximab, eptifibatide, and tirofiban during percutaneous coronary intervention (PCI). Studies on platelet glycoprotein IIb/IIIa receptor inhibitors (GPI) administered as bolus-only during PCI suggest that this strategy may be similar in efficacy, safer, and more cost-effective compared to a bolus plus infusion of GPI. We evaluated 864 patients (abciximab = 274, eptifibatide = 361, and tirofiban = 229) who underwent PCI with a bolus-only regimen during January 2003 to August 2005. After a median follow up of four (interquartile range, 3-4.5) years, there were a total of 95 (11%) deaths. The survival rate was 83% in the abciximab group, 91% in the eptifibatide group, and 93% in the tirofiban group (P = 0.003 by log-rank test). After adjustment for baseline clinical and procedural characteristics using a Cox proportional hazards model, the abciximab group had a significantly higher mortality compared to the eptifibatide group (P = 0.003; Hazard ratio (HR) for eptifibatide compared to abciximab was 0.49 (95% confidence intervals [CI]: 0.30-0.78). The long-term mortality was not significantly different in the tirofiban group compared to the abciximab group (P = 0.33) or the eptifibatide group (P = 0.20), perhaps because of shorter follow-up period and fewer patients in the tirofiban group. When given as bolus-only during PCI, eptifibatide may improve long-term survival compared to abciximab. (c) 2009 Wiley-Liss, Inc.

  14. Reassessment of the unique mode of binding between angiotensin II type 1 receptor and their blockers.

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    Shin-Ichiro Miura

    Full Text Available While the molecular structures of angiotensin II (Ang II type 1 (AT1 receptor blockers (ARBs are very similar, they are also slightly different. Although each ARB has been shown to exhibit a unique mode of binding to AT1 receptor, different positions of the AT1 receptor have been analyzed and computational modeling has been performed using different crystal structures for the receptor as a template and different kinds of software. Therefore, we systematically analyzed the critical positions of the AT1 receptor, Tyr(113, Tyr(184, Lys(199, His(256 and Gln(257 using a mutagenesis study, and subsequently performed computational modeling of the binding of ARBs to AT1 receptor using CXCR4 receptor as a new template and a single version of software. The interactions between Tyr(113 in the AT1 receptor and the hydroxyl group of olmesartan, between Lys(199 and carboxyl or tetrazole groups, and between His(256 or Gln(257 and the tetrazole group were studied. The common structure, a tetrazole group, of most ARBs similarly bind to Lys(199, His(256 and Gln(257 of AT1 receptor. Lys(199 in the AT1 receptor binds to the carboxyl group of EXP3174, candesartan and azilsartan, whereas oxygen in the amidecarbonyl group of valsartan may bind to Lys(199. The benzimidazole portion of telmisartan may bind to a lipophilic pocket that includes Tyr(113. On the other hand, the n-butyl group of irbesartan may bind to Tyr(113. In conclusion, we confirmed that the slightly different structures of ARBs may be critical for binding to AT1 receptor and for the formation of unique modes of binding.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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

    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...... Stroke Scale score at 7 days and Barthel index at 6 months), and there was no evidence of a differential effect in any of the prespecified subgroups. During follow-up, nine (1%) patients on candesartan and five (renal failure was reported for 18 (2......BACKGROUND: Raised blood pressure is common in acute stroke, and is associated with an increased risk of poor outcomes. We aimed to examine whether careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised...

  17. Antihypertensive efficacy and safety of the angiotensin receptor blocker azilsartan in elderly patients with hypertension.

    Science.gov (United States)

    Kamada, Tomohito; Hayashi, Mutsuharu; Fujiwara, Wakaya; Yoshikawa, Daiji; Mukaide, Daisuke; Sugishita, Yoshinori; Yoshinaga, Masataka; Itoh, Takehiro; Yokoi, Hiroatsu; Ishii, Junichi; Watanabe, Eiichi; Ozaki, Yukio; Izawa, Hideo

    2017-01-01

    The number of elderly patients with hypertension has been steadily increasing. However, there are limited data on the safety and efficacy of the new angiotensin type 1 receptor blocker (ARB) azilsartan in elderly patients with hypertension. We investigated the clinical efficacy and safety of azilsartan in this population. The study population comprised 56 ambulatory patients with essential hypertension. We evaluated the reduction in blood pressure and safety after 12 weeks of treatment with azilsartan in 29 hypertensive patients ≥65 years of age (aged group) in comparison with the findings in 27 patients elderly patients and may be safe. Therefore, azilsartan could be a valuable option for treating hypertension in elderly and non-elderly patients.

  18. 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

  19. Comparing the effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on renal function decline in diabetes

    NARCIS (Netherlands)

    Huang, Yunyu; Haaijer-Ruskamp, Flora M.; Voorham, Jaco

    Aim: To compare effectiveness of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) for protecting Type 2 diabetes mellitus (DM2) patients from renal function decline in a real-world setting. Methods: Retrospective cohort study of new ACEi/ARB users in 2007-2012 in

  20. Molecular targeting therapy with angiotensin II receptor blocker for prostatic cancer

    Directory of Open Access Journals (Sweden)

    Hiroji Uemura

    2011-12-01

    Full Text Available Angiotensin II (Ang-II plays a key role as a vasoconstrictor in controlling blood pressure and electrolyte/fluid homeostasis. Recently it has also been shown that this peptide is a cytokine, acting as a growth factor in cardiovascular and stromal cells. In addition, the physiological function of Ang-II seems to be similar in prostate cancer and stromal cells. It is widely assumed that Ang-II facilitates the growth of both cells, and its receptor blockers (ARBs have the potential to inhibit the growth of various cancer cells and tumors through the Ang-II receptor type 1 (AT1 receptor. The mechanism of cell growth inhibition by ARBs has been considered to be that of suppression of the signal transduction systems activated by growth factors or cytokines in prostate cancer cells, and suppression of angiogenesis. This review highlights the possible use of ARBs as novel agents for prostatic diseases including prostate cancer and benign hypertrophy, and covers related literature.

  1. Long-term results following switch from abciximab to eptifibatide during percutaneous coronary intervention.

    Science.gov (United States)

    Koutouzis, Michael; Lagerqvist, Bo; Oldgren, Jonas; Akerblom, Axel; Wahlin, Magnus; Karlsson, Thomas; Albertsson, Per; Matejka, Göran; Grip, Lars

    2010-11-01

    The usage of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors improves the outcome during high-risk percutaneous coronary interventions (PCI). The aim of this study was to evaluate the long-term effects after a planned switch from abciximab to eptifibatide during PCI. A switch from the general use of abciximab to eptifibatide as a GP IIb/IIIa in connection with PCI would not have any negative effects on long-term clinical outcomes. To reduce costs, a general switch from abciximab to eptifibatide was instituted in 2004 in 2 university hospitals in Sweden. All patients treated 6 months before and 6 months after the switch were followed for 30 months. During the study period, 1038 patients underwent PCI and received a GP IIb/IIIa receptor inhibitor, 481 (46%) before the switch (Group A) and 557 (54%) after the switch (Group B). The 2 groups had similar baseline characteristics. The primary endpoint was the composite of death, myocardial infarction, stroke, or new coronary revascularization (percutaneous or surgical); secondary endpoints were the individual components of this composite. A separate analysis was performed on patients treated for ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction/unstable angina, and diabetes, respectively. Data were collected from the Swedish Coronary Angiography and Angioplasty Registry. There were no differences between the groups in the primary endpoint (29.7% in Group A vs 29.3% in Group B; P = 0.48) or in any of the secondary endpoints. A switch from the general usage of abciximab to eptifibatide as a GP IIb/IIIa receptor inhibitor in connection with PCI did not seem to have any negative effects on long-term clinical outcomes. Copyright © 2008 Wiley Periodicals, Inc.

  2. Angiotensin-converting enzyme inhibitors reduce mortality compared to angiotensin receptor blockers: Systematic review and meta-analysis.

    Science.gov (United States)

    Salvador, Gabriel Lo; Marmentini, Vinicius M; Cosmo, Willian R; Junior, Emilton L

    2017-12-01

    Background There are few reviews comparing the long-term outcomes of the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in a hypertensive population because both are effective in reducing blood pressure. None of them compared angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers with a placebo group in patients with essential hypertension, because few studies exist with this design. Methods A systematic search of PUBMED, LILACS, SCIELO, ICTRP, Cochrane, EMBASE and ClinicalTrials.gov from 1 January 2000 until 31 December 2015 selected prospective studies that reported an association between the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in the following cardiovascular outcomes: heart failure/hospitalisation, stroke, acute myocardial infarction, total cardiovascular deaths, total deaths and total outcomes. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were combined by using a fixed-effects model. Results Seventeen studies ( n = 73,761) were included of which 12 studies were randomly assigned to angiotensin II receptor blocker therapy ( n = 24,697) and five to angiotensin-converting enzyme inhibitors ( n = 12,170). Angiotensin-converting enzyme inhibitors proved to be significant in reducing total deaths (OR 0.85, 95% CI 0.78-0.93) and cardiovascular deaths (OR 0.77, 95% CI 0.69-0.87). Angiotensin II receptor blocker therapy did not show a reduction in total deaths (OR 1.02, 95% CI 0.96-1.09) or cardiovascular deaths (OR 0.95, 95% CI 0.86-1.06). For acute myocardial infarction, stroke and heart failure/hospitalisation, the reductions were significant for both classes. Conclusion Angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use is similar in preventing major cardiovascular outcomes regarding acute myocardial infarction, stroke and heart failure/hospitalisation. However, the use of angiotensin-converting enzyme

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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. 

  5. Use of beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta-analysis.

    Science.gov (United States)

    Raimondi, Sara; Botteri, Edoardo; Munzone, Elisabetta; Cipolla, Carlo; Rotmensz, Nicole; DeCensi, Andrea; Gandini, Sara

    2016-07-01

    Breast cancer (BC) is the second leading cause of cancer death among women in Western Countries. Beta-blocker (BB) drugs, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were suggested to have a favorable role in the development and progression of BC. We have performed a meta-analysis to clarify the potential benefits of these drugs on BC survival. A total number of 46 265 BC patients from eleven papers were included, ten independent studies on BB use and seven on ACEi/ARB use. The summary hazard ratio (SHR) was estimated by pooling the study-specific estimates with random effects models and maximum likelihood estimation. We assessed the homogeneity of the effects across studies and evaluated between-study heterogeneity by meta-regression and sensitivity analyses. We found a significant improvement in BC specific survival for patients treated with BB drugs at the time of BC diagnosis (SHR: 0.44; 95%CI: 0.26-0.73 with I(2) = 78%). We also observed a borderline significant improvement in disease free survival for subjects treated with BB (SHR: 0.71, 95%CI: 0.19-1.03). No association of ACEi/ARB use with disease free and overall survival was found. In conclusion, we report epidemiological evidence that BB improve BC-specific survival. Clinical trials addressing this hypothesis are warranted. © 2016 UICC.

  6. Comparison of the AT1-receptor blockers candesartan, irbesartan and losartan for inhibiting renal microvascular constriction

    Directory of Open Access Journals (Sweden)

    William F van Rodijnen

    2001-03-01

    Full Text Available Angiotensin II (Ang II type 1 (AT1 receptor blockers differ in their affinity for the AT1-receptor, suggesting a dissimilar potency for inhibiting Ang II-induced vascular constriction. In the present study, we compared the effects of candesartan, irbesartan and losartan on the renal microvascular constriction to locally-formed Ang II, using isolated, perfused hydronephrotic rat kidneys. Addition of 1 nmol/L angiotensin I (Ang I, the precursor of Ang II significantly reduced the diameters of interlobular arteries (ILAs; -47.6±2.6%, afferent arterioles (AAs; -43.6±2.3% and efferent arterioles (EAs; -31.6±2.4%. Candesartan and irbesartan were more potent in antagonising the constriction to Ang I than losartan. By contrast, candesartan and irbesartan differed only slightly in potency. After a washing period of 60 minutes with drug-free medium, a second application of Ang I failed to induce vasoconstriction only in candesartan-treated kidneys. Pretreatment of hydronephrotic kidneys with candesartan, to further explore its antagonistic properties, shifted the dose-response curves of Ang II approximately 2 log units to the right without reducing the maximal Ang II-induced constriction of ILAs, AAs or EAs. Additionally, dose-response curves of Ang II were similar after short (10 minutes and prolonged (60 minutes preincubation with candesartan. Our findings indicate that candesartan and irbesartan are more potent inhibitors of renal microvascular constriction to locally-formed Ang II than losartan. The inhibitory effect of candesartan is more prolonged, suggesting a slow dissociation from the AT1-receptor. Additionally, candesartan was found to block the Ang II-induced constriction of renal microvessels in a surmountable manner.

  7. Regression of experimental endometriotic implants in a rat model with the angiotensin II receptor blocker losartan.

    Science.gov (United States)

    Cakmak, Bulent; Cavusoglu, Turker; Ates, Utku; Meral, Ayfer; Nacar, Mehmet Can; Erbaş, Oytun

    2015-04-01

    Endometriosis is a common disease in women of reproductive age, and many different treatments have been developed, although none has provided a cure. In this study, the efficacy of losartan, an angiotensin II type 1 receptor blocker and an antiangiogenic and anti-inflammatory agent, on regression of experimental endometriotic implants in a rat model was investigated. Peritoneal endometriosis was surgically induced in 16 mature female Sprague-Dawley rats. The peritoneal endometriotic implant was confirmed after 28 days, and the animals were divided randomly into two groups. The control group (n = 8) was given 4 mL/day tap water by oral gavage, and the losartan group (n = 8) was given 20 mg/kg per day losartan p.o. We compared endometriotic implant size, extent and severity of adhesion, as well as plasma and peritoneal lavage fluid cytokine levels including vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α, plasma inflammatory factor pentraxin-3 (PTX-3) and C-reactive protein (CRP) between the treatment groups. Mean surface endometriotic area, histological score of implants, adhesion formation, plasma VEGF, TNF, PTX-3 and CRP levels were significantly lower in the losartan group compared with control (P losartan group than in the control group (P 0.05). Losartan suppressed the implant surface area of experimental endometriosis in rats and reduced the levels of plasma VEGF, TNF-α, PTX-3 and CRP. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  8. Carotid intima-media thickness and anti-hypertensive treatment: Focus on angiotensin II receptor blockers.

    Science.gov (United States)

    Cuspidi, Cesare; Sala, Carla; Tadic, Marijana; Grassi, Guido; Mancia, Giuseppe

    2018-01-20

    Carotid intima-media thickness (CIMT), as assessed by ultrasonography, has been shown to be directly related to cardiovascular (CV) morbidity and mortality independently of conventional risk factors. Thus, CIMT has been proposed as a marker of CV risk and a surrogate end-point for therapeutic interventions. In the present article we will review available literature about CIMT clinical/prognostic significance in order to offer an updated comprehensive information on this topic. In particular, the anti-atherosclerotic effect of angiotensin II receptor blockers (ARBs) in the hypertensive setting will be addressed, based on findings provided by double blind, randomized, prospective studies comparing CIMT longitudinal changes. Our review, including 8 studies totaling 1154 hypertensive participants, shows that ARBs are as effective as the other classes of antihypertensive drugs in preventing/regressing subclinical carotid damage and that findings supporting their superiority in this field are limited and not univocal. Future studies aimed to clarify the therapeutic impact of ARBs on CIMT changes and their prognostic implications are warranted. Copyright © 2018. Published by Elsevier Ltd.

  9. Drug Interactions with Angiotensin Receptor Blockers: Role of Human Cytochromes P450.

    Science.gov (United States)

    Yang, Ruirui; Luo, Zhiqiang; Liu, Yang; Sun, Mohan; Zheng, Ling; Chen, Yingying; Li, Yanping; Wang, Hao; Chen, Lingzhu; Wu, Ming; Zhao, Huihui

    2016-01-01

    Angiotensin receptor blockers (ARBs) are the most recent class of agents for the treatment of hypertension. However, ARBs may cause a low incidence of headache, upper respiratory infection, back pain, muscle cramps, fatigue, dizziness, and many other side effects. In some cases, such toxicity is associated with pharmacokinetic alterations. The cytochrome P450 (CYP) enzyme system plays an important role in a lot of clinically important pharmacokinetic drug interactions. To identify relevant studies on drug-drug and food-drug pharmacokinetic interactions with the ARBs, a literature search of Google Scholar was performed from January 1994 to June 2015, with the following keywords: 'losartan', 'valsartan,' 'candesartan,' 'irbesartan,' 'telmisartan,' 'eprosartan,' 'olmesartan,' and 'azilsartan', combined with the keyword 'pharmacokinetic interactions' and 'CYP'. Based on the literatures published, it has been demonstrated that pharmacokinetic interactions of losartan with other agents are mainly via CYP2C9- and CYP3A4-mediated, the role played by CYP enzyme system in the metabolism of valsartan, candesartan, irbesartan, and azilsartan appears modest, and cytochrome P450 system has no influence on the metabolism of telmisartan, eprosartan, olmesartan. Therefore, according to these pharmacokinetic findings, no dosage adjustment is recommended when eprosartan, telmisartan and olmesartan are combined with other pharmacological agents in patients with hypertension. This review summarize the available data on cytochrome P450 - related drug-drug interactions reported in the literature for the eight ARBs. Knowledge of the pharmacokinetic properties of the ARBs should allow the avoidance of the majority of drug interactions without compromising therapeutic benefits.

  10. Angiotensin Receptor Blocker Losartan Inhibits Spontaneous Motility of Isolated Human Ureter.

    Science.gov (United States)

    Jankovic, Slobodan M; Stojadinovic, Dobrivoje; Stojadinovic, Miroslav; Jankovic, Snezana V; Djuric, Janko M; Stojic, Isidora; Kostic, Marina

    2016-12-01

    Ureteral motility is essential for elimination of intraluminal stones, and it may be adversely affected by cardiovascular drugs that a patient is taking chronically. The aim of our study was to test whether ACE inhibitors and an angiotensin receptor blocker may influence spontaneous contractions of isolated human ureter. Both phasic and tonic contractions of the isolated ureteral segments taken from 10 patients were measured as changes of the longitudinal tension or pressure recordings. Captopril, enalapril and losartan were separately added to the organ baths cumulatively. While enalapril (2.7 × 10 -7 -3.9 × 10 -4  M) and captopril (6.1 × 10 -7 -2.7 × 10 -3  M) did not affect either spontaneous activity or tone of isolated ureteral segments, losartan (2.9 × 10 -7 -4.2 × 10 -4  M) caused concentration-dependent inhibition of spontaneous contractions of the segments (50 % effective concentration (EC 50 ) = 13.46 ± 1.80 × 10 -6  M; F = 10.72, r = 0.79, p ureter.

  11. The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

    Directory of Open Access Journals (Sweden)

    Myla E. Moretti

    2012-01-01

    Full Text Available Angiotensin converting enzyme (ACE inhibitors and angiotensin II receptor blockers (ARBs are known to cause fetal renal damage in pregnancy. Due to conflicting reports in the literature, their safety after first trimester exposure has been debated. Our aim was to determine whether the use of ACE inhibitors or ARBs in the first trimester of pregnancy is associated with an increased risk for major malformations or other adverse outcomes. All subjects were prospectively enrolled from among women contacting a teratogen information service. At initial contact, details of maternal medical history and exposures were collected and follow-up interviews were conducted to ascertain pregnancy outcomes. Two comparator groups, women with hypertension treated with other antihypertensives, and healthy controls were also recruited. Baseline maternal characteristics were not different among the three groups. There were no differences in rates of major malformations. Both the ACE-ARBs and disease-matched groups exhibited significantly lower birth weight and gestational ages than the healthy controls (P<0.001 for both variables. There was a significantly higher rate of miscarriage noted in the ACE/ARB group (P<0.001. These results suggest that ACE inhibitors/ARBs are not major human teratogens; however, they may be associated with an increased risk for miscarriage.

  12. Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin

    Directory of Open Access Journals (Sweden)

    Pieter Spincemaille

    2014-10-01

    Full Text Available The human pathology Wilson disease (WD is characterized by toxic copper (Cu accumulation in brain and liver, resulting in, among other indications, mitochondrial dysfunction and apoptosis of hepatocytes. In an effort to identify novel compounds that can alleviate Cu-induced toxicity, we screened the Pharmakon 1600 repositioning library using a Cu-toxicity yeast screen. We identified 2 members of the drug class of Angiotensin II Type 1 receptor blockers (ARBs that could increase yeast tolerance to Cu, namely Candesartan and Losartan. Subsequently, we show that specific ARBs can increase yeast tolerance to Cu and/or the chemotherapeutic agent cisplatin (Cp. The latter also induces mitochondrial dysfunction and apoptosis in mammalian cells. We further demonstrate that specific ARBs can prevent the prevalence of Cu-induced apoptotic markers in yeast, with Candesartan Cilexetil being the ARB which demonstrated most pronounced reduction of apoptosis-related markers. Next, we tested the sensitivity of a selection of yeast knockout mutants affected in detoxification of reactive oxygen species (ROS and Cu for Candesartan Cilexetil rescue in presence of Cu. These data indicate that Candesartan Cilexetil increases yeast tolerance to Cu irrespectively of major ROS-detoxifying proteins. Finally, we show that specific ARBs can increase mammalian cell tolerance to Cu, as well as decrease the prevalence of Cu-induced apoptotic markers. All the above point to the potential of ARBs in preventing Cu-induced toxicity in yeast and mammalian cells.

  13. Candesartan, angiotensin II type 1 receptor blocker is able to relieve age-related cognitive impairment.

    Science.gov (United States)

    Trofimiuk, Emil; Wielgat, Przemysław; Braszko, Jan J

    2017-07-21

    Candesartan is one of the standard antihypertensive drug belonging to AT1R angiotensin receptor blockers (ARBs) group. Beneficial effects of this drug in the treatment of hypertension are well recognized. In this study we tested a hypothesis that candesartan could alleviate age-related memory decline. Aged and young rats have been treated with candesartan (0.1 mg kg-1) for 21 days and then underwent a battery of behavioral tests: for assessment of long-term memory (Passive avoidance test - PA), recognition memory (Object recognition test - OR), locomotor functions (Open field - OF) and anxiety behavior (Elevated plus maze - EPM). Aged rats (2-years-old) displayed clear declining tendency in the retrieval of passive avoidance behavior showing thus increased forgetting. Prolonged administration of candesartan significantly (p candesartan significantly improved recognition memory (p candesartan potently abolishes some kinds of aging-induced memory impairments and cognitive declines in aged rats, but in some circumstances it may even could increase the damage of memory. It seems that the use of sartans in the treatment of hypertension for patients with associated cognitive impairment, or for people in risk groups for such disorders can be an interesting alternative. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. 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 diabetes mellitus.

  15. Randomized comparison of eptifibatide versus abciximab in primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: results of the EVA-AMI Trial.

    Science.gov (United States)

    Zeymer, Uwe; Margenet, Alain; Haude, Michael; Bode, Christoph; Lablanche, Jean-Marc; Heuer, Hubertus; Schröder, Rolf; Kropff, Stefan; Bourkaib, Ryad; Banik, Norbert; Zahn, Ralf; Teiger, Emmanuel

    2010-08-03

    The aim of this study was to compare eptifibatide and abciximab as adjuncts to primary percutaneous coronary intervention (PCI). The glycoprotein (GP) IIb/IIIa receptor inhibitor abciximab as adjunct to primary PCI in patients with ST-segment elevation myocardial infarctions has been shown to reduce ischemic complications and improve clinical outcomes. So far, no trial has been performed to compare the efficacy of another GP IIb/IIIa receptor inhibitor, eptifibatide, and abciximab in primary PCI. A total of 427 patients with ST-segment elevation myocardial infarctions eptifibatide (n = 226) followed by a 24-h infusion or single-bolus abciximab (n = 201) followed by a 12-h infusion. In this noninferiority trial, the primary end point was the incidence of complete (> or =70%) ST-segment resolution (STR) 60 min after PCI, a measure of myocardial reperfusion. The assumption was a 60% complete STR rate in the abciximab group. The noninferiority margin was set to 15%. The incidence of complete STR at 60 min after PCI in the intention-to-treat analysis was 62.6% after eptifibatide and 56.3% after abciximab (adjusted difference: 7.1%; 95% confidence interval: 2.7% to 17.0%). All-cause mortality 6.2% versus 4.5% (p = 0.50); reinfarction 0.4% versus 3.5% (p = 0.03); target vessel revascularization 4.4% versus 6.5% (p = 0.40); the combined end point of death, nonfatal reinfarction, and target vessel revascularization 10.6% versus 10.9% (p = 0.90); stroke 0.5% versus 0.5% (p = 1.00) after 6 months; and Thrombolysis In Myocardial Infarction major bleeding complications 4.0% versus 2.0% (p = 0.20) after 30 days were observed after eptifibatide and abciximab, respectively. Eptifibatide as an adjunct to primary PCI is equally as effective as abciximab with respect to STR. (Efficacy of Eptifibatide Compared to Abciximab in Primary Percutaneous Coronary Intervention [PCI] for Acute ST Elevation Myocardial Infarction [STEMI]; NCT00426751). Copyright (c) 2010 American College of

  16. 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.

  17. Comparative effect of angiotensin II type I receptor blockers and calcium channel blockers on laboratory parameters in hypertensive patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Nishida Yayoi

    2012-05-01

    Full Text Available Abstract Background Both angiotensin II type I receptor blockers (ARBs and calcium channel blockers (CCBs are widely used antihypertensive drugs. Many clinical studies have demonstrated and compared the organ-protection effects and adverse events of these drugs. However, few large-scale studies have focused on the effect of these drugs as monotherapy on laboratory parameters. We evaluated and compared the effects of ARB and CCB monotherapy on clinical laboratory parameters in patients with concomitant hypertension and type 2 diabetes mellitus. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and July 31, 2011, to identify cohorts of new ARB users (n = 601 and propensity-score matched new CCB users (n = 601, with concomitant mild to moderate hypertension and type 2 diabetes mellitus. We used a multivariate-adjusted regression model to adjust for differences between ARB and CCB users, and compared laboratory parameters including serum levels of triglyceride (TG, total cholesterol (TC, non-fasting blood glucose, hemoglobin A1c (HbA1c, sodium, potassium, creatinine, alanine aminotransferase (ALT, aspartate aminotransferase (AST, gamma-glutamyltransferase (GGT, hemoglobin and hematocrit, and white blood cell (WBC, red blood cell (RBC and platelet (PLT counts up to 12 months after the start of ARB or CCB monotherapy. Results We found a significant reduction of serum TC, HbA1c, hemoglobin and hematocrit and RBC count and a significant increase of serum potassium in ARB users, and a reduction of serum TC and hemoglobin in CCB users, from the baseline period to the exposure period. The reductions of RBC count, hemoglobin and hematocrit in ARB users were significantly greater than those in CCB users. The increase of serum potassium in ARB users was significantly greater than that in CCB users. Conclusions Our study suggested that hematological adverse effects and

  18. Angiotensin Converting-Enzyme Inhibitors, Angiotensin Receptor Blockers, and Calcium Channel Blockers Are Associated with Prolonged Vascular Access Patency in Uremic Patients Undergoing Hemodialysis.

    Directory of Open Access Journals (Sweden)

    Fu-An Chen

    Full Text Available Vascular access failure is a huge burden for patients undergoing hemodialysis. Many efforts have been made to maintain vascular access patency, including pharmacotherapy. Angiotensin converting enzyme inhibitor (ACE-I, angiotensin receptor blocker (ARB, and calcium channel blocker (CCB are known for their antihypertensive and cardio-protective effects, however, their effects on long-term vascular access patency are still inconclusive.We retrospectively enrolled patients commencing maintenance hemodialysis between January 1, 2000, and December 31, 2006 by using National Health Insurance Research Database in Taiwan. Primary patency was defined as the date of first arteriovenous fistula (AVF or arteriovenous graft (AVG creation to the time of access thrombosis or any intervention aimed to maintain or re-establish vascular access patency. Cox proportional hazards models were used to adjust the influences of patient characteristics, co-morbidities and medications.Total 42244 patients were enrolled in this study, 37771 (89.4% used AVF, 4473 (10.6% used AVG as their first long term dialysis access. ACE-I, ARB, and CCB use were all associated with prolonged primary patency of AVF [hazard ratio (HR 0.586, 95% confidence interval (CI 0.557-0.616 for ACE-I use; HR 0.532, CI 0.508-0.556 for ARB use; HR 0.485, CI 0.470-0.501 for CCB use] and AVG (HR 0.557, CI 0.482-0.643 for ACE-I use, HR 0.536, CI 0.467-0.614 for ARB use, HR 0.482, CI 0.442-0.526 for CCB use.In our analysis, ACE-I, ARB, and CCB were strongly associated with prolonged primary patency of both AVF and AVG. Further prospective randomized studies are still warranted to prove the causality.

  19. [Drug therapy of benign prostatic hyperplasia. Is combination therapy with 5 alpha-reductase inhibitors and alpha-receptor blockers effective?].

    Science.gov (United States)

    Horninger, W; Bartsch, G

    2002-09-01

    5 alpha-reductase inhibitors and alpha 1-receptor blockers are the two main drug therapies used in the management of symptomatic benign prostatic hyperplasia. As alpha-reductase inhibitors and alpha 1-receptor blockers act through different mechanisms, a combination of the two agents might be promising. The potential benefits of combination therapy with selective alpha 1-receptor blockers and finasteride, a 5 alpha-reductase inhibitor, are currently being evaluated in several placebo-controlled prospective multicenter studies (VA Study, ALFIN Study, PREDICT Study, and MTOPS Study). The data from these studies available so far demonstrate a statistically significant benefit for the study groups receiving alpha 1-receptor blockers and combination therapy vs placebo and finasteride monotherapy in terms of symptom scores and peak urine flow rates. However, none of the studies yielded a statistically significant advantage of combination therapy over treatment with alpha 1-receptor blockers. These results should be interpreted with reference to the prostatic volume, which in the studies mentioned above was relatively low. From the results of all these studies, it can be concluded that in symptomatic patients with prostate volumes of up to 40-45 ml a combination of 5 alpha-reductase inhibitors with alpha 1-receptor blockers does not appear to provide any benefit. Yet, it can be assumed that in symptomatic patients with prostate volumes of more than 60 ml combination therapy may indeed prove more effective.

  20. On the use of abciximab in percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Iversen, Allan

    2011-01-01

    holds data on vital status; and 3) The Danish National Board of Health´s National Patient Registry which holds data on discharge ICD-10 codes and thus clinical endpoints. By doing so, we were able to evaluate the efficacy in the three following settings: • ACS patients with diabetes (paper IV): 5...... with ACS who were older or equal 70 years of age did not seem to have the mortality benefit of abciximab seen in patients younger than 70 years of age. Paper V. • Among STEMI patients treated with pPCI, only those who had a complex lesion assessed by diagnostic coronary angiography had a mortality benefit...... to have a higher risk of bleeding complication when treated with abciximab. • Since only STEMI patients with complex lesions benefitted from abciximab, a diagnostic angiogram should be performed in order to characterize the lesion before treatment with abciximab is initiated in STEMI patients...

  1. Efficacy and mechanism of angiotensin II receptor blocker treatment in experimental abdominal aortic aneurysms.

    Directory of Open Access Journals (Sweden)

    Yasunori Iida

    Full Text Available BACKGROUND: Despite the importance of the renin-angiotensin (Ang system in abdominal aortic aneurysm (AAA pathogenesis, strategies targeting this system to prevent clinical aneurysm progression remain controversial and unproven. We compared the relative efficacy of two Ang II type 1 receptor blockers, telmisartan and irbesartan, in limiting experimental AAAs in distinct mouse models of aneurysm disease. METHODOLOGY/PRINCIPAL FINDINGS: AAAs were induced using either 1 Ang II subcutaneous infusion (1000 ng/kg/min for 28 days in male ApoE(-/- mice, or 2 transient intra-aortic porcine pancreatic elastase infusion in male C57BL/6 mice. One week prior to AAA creation, mice started to daily receive irbesartan (50 mg/kg, telmisartan (10 mg/kg, fluvastatin (40 mg/kg, bosentan (100 mg/kg, doxycycline (100 mg/kg or vehicle alone. Efficacy was determined via serial in vivo aortic diameter measurements, histopathology and gene expression analysis at sacrifice. Aortic aneurysms developed in 67% of Ang II-infused ApoE(-/- mice fed with standard chow and water alone (n = 15, and 40% died of rupture. Strikingly, no telmisartan-treated mouse developed an AAA (n = 14. Both telmisartan and irbesartan limited aneurysm enlargement, medial elastolysis, smooth muscle attenuation, macrophage infiltration, adventitial neocapillary formation, and the expression of proteinases and proinflammatory mediators. Doxycycline, fluvastatin and bosentan did not influence aneurysm progression. Telmisartan was also highly effective in intra-aortic porcine pancreatic elastase infusion-induced AAAs, a second AAA model that did not require exogenous Ang II infusion. CONCLUSION/SIGNIFICANCE: Telmisartan suppresses experimental aneurysms in a model-independent manner and may prove valuable in limiting clinical disease progression.

  2. Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

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    Motoharu Hayashi

    Full Text Available A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1, tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1 and glucose transporter 4 (GLUT4 in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results

  3. Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease

    National Research Council Canada - National Science Library

    Lincoff, A.Michael; Califf, Robert M; Topol, Eric J

    2000-01-01

    .... Intravenous agents directed against this receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide and nonpeptide mimetics tirofiban and lamifiban...

  4. The influence of alpha-adrenergic receptors stimulator and blockers and beta-blocker on the ovary and endocrinological activity in heifers during superovulation.

    Science.gov (United States)

    Gajewski, Z; Thun, R; Faundez, R; Pawliński, B

    2006-11-01

    Twenty five Holstein-Friesian heifers, clinically normal and with regular oestrous cycles, were used for induction of superovulation (PMSG-PGF(2)alpha-Neutra-PMSG). Animals were divided into 5 groups receiving: I - detomidine (40 microg/kg b.w.), II - doxazosin (0.2 mg/kg b.w.), III - yohimbine HCL 1% (1 ml/50 kg b.w.), IV - carazolol (0.01 mg/ kg b.w., i.v.), and V - physiological saline (1 ml/50 kg b.w.). The heifers with PGF2 alpha-induced cycles were treated with the substances 88 hrs after being given a single i.m. injection of 2500 IU PMSG. All animals were examined by ultrasonography, and by the number and size of ovarian follicles > 3 mm in diameter. The follicles were divided into 3 groups according to the diameter. Blood plasma was stored at -20 degrees C until LH, P4, E2 and PGFM analyses. In the control (V) group, two waves of follicle growth were observed. Yohimbine produced a significant blockage of ovulation. The mean number of corpora lutea in the group III was significantly lower than that in the control group (palpha-2 adrenergic receptors antagonist. Yohimbinum administration did not affect plasma concentration of examined hormones. There was a difference between the plasma levels of LH after the doxazosin injection. Single injection of the stimulators and blockers of adrenergic receptors did not affect superovulatory response in terms of the numbers of CL, unruptured follicles and embryos recovered. The affectivity of artificial insemination was not significantly different between the control group and the detomidinum groups, while in the yohimbinum group it was significantly lower.

  5. The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i.

    Science.gov (United States)

    Cseplo, Peter; Vamos, Zoltan; Ivic, Ivan; Torok, Orsolya; Toth, Attila; Koller, Akos

    2016-01-01

    Nebivolol is known to have beta-1 blocker activity, but it was also suggested that it elicits relaxation of the peripheral arteries in part via release of nitric oxide (NO). However, the effect of nebivolol on the vasomotor tone of cerebral arteries is still unclear. To assess the effects of nebivolol on the diameter of isolated rat basilar arteries (BA) in control, in the presence of inhibitors of vasomotor signaling pathways of know action and hemolysed blood. Vasomotor responses were measured by videomicroscopy and the intracellular Ca2+ by the Fura-2 AM ratiometric method. Under control conditions, nebivolol elicited a substantial dilation of the BA (from 216±22 to 394±20 μm; pblocker). Dilatation of BA was also affected by beta-2 receptor blockade with butoxamine, but not by the guanylate cyclase blocker ODQ. Interestingly, beta-1 blockade by atenolol inhibited nebivolol-induced dilation. Also, the BKCa channel blocker iberiotoxin and KCa channel inhibitor TEA significantly reduced nebivolol-induced dilation. Nebivolol significantly reduced smooth muscle Ca2+ level, which correlated with the increases in diameters and moreover it reversed the hemolysed blood-induced constriction of BA. Nebivolol seems to have an important dilator effect in cerebral arteries, which is mediated via several vasomotor mechanisms, converging on the reduction of smooth muscle Ca2+ levels. As such, nebivolol may be effective to improve cerebral circulation in various diseased conditions, such as hemorrhage.

  6. Switch from abciximab to eptifibatide during percutaneous coronary intervention.

    Science.gov (United States)

    Wahlin, Magnus; Albertsson, Per; Karlsson, Thomas; Matejka, Göran; Odell, Annika; Tahmasebiepour, Farshad; Wolmeryd, Christina; Grip, Lars

    2009-05-29

    Treatment with glycoprotein (GP) IIb/IIIa inhibitors during percutaneous coronary intervention (PCI) reduce ischemic complications and improve outcome. Of the GPIIb/IIIa inhibitors abciximab is better documented than eptifibatide, but the former is more expensive. The aim of this study was to monitor a switch from abciximab to eptifibatide with respect to clinical outcome up to six months after PCI. All consecutive patients that six months before and six months after a switch from abciximab to eptifibatide received GPIIb/IIIa inhibitors during and after de novo PCIs were followed for six months with respect to clinical outcome. 310 patients received abciximab and 350 eptifibatide. Baseline characteristics were similar in the two groups. 55% of the patients underwent PCI for acute ST-elevation myocardial infarction and 41% for unstable coronary artery disease. There were trends for lower mortality among abciximab-treated than among the eptifibatide-treated patients during in-hospital stay (0.6% vs 2.0%:NS) as well as during the six month follow up (2.3% vs 3.7%:NS). The combined endpoint of death, myocardial infarction, stroke, repeated revascularisation and serious bleeding occurred in 14.9% in the abciximab group vs 16.8% in the eptifibatide group (NS). The study could not demonstrate any significant deterioration of clinical results after a switch from abciximab to eptifibatide as routine GPIIb/IIIa inhibition during PCI. With respect to the limited number of patients a clinical significant difference between the two GPIIb/IIIa inhibitors cannot, however, be excluded.

  7. Comparative efficacy of eptifibatide and abciximab in primary angioplasty study

    Directory of Open Access Journals (Sweden)

    Rohan Jayasinghe

    2011-02-01

    Full Text Available Rohan Jayasinghe1 Matias Yudi1 Sanjay Jayasinghe21Cardiology Department, Gold Coast Hospital, Griffith University, Queensland, Australia; 2Centre for Immunisation Research, Sydney, AustraliaBackground: Primary percutaneous intervention is the safest and most effective treatment modality for acute ST-segment elevation myocardial infarction (MI in centers where catheterization facilities exist. Intravenous glycoprotein IIb/IIIa inhibitor therapy during the procedures has been proven to provide added benefits. For the two agents, abciximab and eptifibatide, commonly used in this context, there is only limited comparative data available for the clinicians. Hitherto, there is no data published from the Asia–Pacific region on this topic.Method: A retrospective comprehensive analysis was carried out, comparing patients who were treated with abciximab (n = 125 and eptifibatide (n = 125 during primary angioplasty over a 3-year period. The primary outcome measure was in-hospital mortality. The other outcome measures studied include MI, stroke, blood transfusion, contrast nephropathy, significant bleeding, and vascular complications. A comparative cost analysis was carried out to ascertain the average overall differential cost.Results: In-hospital mortality, MI, stroke, blood transfusion, contrast nephropathy, significant bleeding, and vascular complication were observed at a higher rate in the patients who were treated with abciximab. However, these differences did not reach statistical significance. Due to the higher cost per unit and longer hospital stay, therapy with abciximab costs more than that with eptifibatide.Conclusions: Both abciximab and eptifibatide are safe and effective adjunct therapeutic agents in the setting of primary angioplasty. However, there is a trend toward higher adverse event with the former agent that was not statistically significant. Therapy with abciximab costs more per patient.Keywords: abciximab, eptifibatide, PCI, STEMI

  8. Angiotensin II receptor blockers and risk of acute pancreatitis - a population based case-control study in Sweden.

    Science.gov (United States)

    Bexelius, Tomas S; Ljung, Rickard; Mattsson, Fredrik; Lu, Yunxia; Lindblad, Mats

    2017-03-07

    Acute pancreatitis is a potentially lethal disease, with a rising incidence in the Western world. Yet, no pharmacological prevention or specific treatment for acute pancreatitis exists. Also, the connection with severity of acute pancreatitis is unknown. Experimental and epidemiological research suggests a protective effect of angiotensin II receptor blockers. During 2006 to 2008, we performed a nationwide case-control study on Swedish residents aged 40-84 years. First-time cases with acute pancreatitis were identified in the National Patient Register and data on dispensed prescriptions was retrieved from the Prescribed Drug Register. Controls were randomly selected from the general population in Sweden frequency-matched on sex, age, and calendar year. To estimate relative risk of acute pancreatitis, by degree of severity, among users of angiotensin II receptor blockers, as compared to non-users, we used multivariable logistic regression analysis to calculate odds ratios (OR) with 95% confidence interval (CI). Among 6,161 cases of acute pancreatitis and 61,637 controls, current use of angiotensin II receptor blockers was followed by a decreased risk of acute pancreatitis, compared to non-users, adjusted OR 0 · 77 (95% CI 0 · 69-0 · 86). No protective association, but an increased risk was found for users of angiotensin-converting enzyme inhibitors (adjusted OR 1 · 11, 95% CI: 1 · 01-1 · 21), analysed for comparison reasons. There was a significant decreased risk associated with both severe acute pancreatitis, (OR 0 · 71 (0 · 59-0 · 85), and mild acute pancreatitis; adjusted OR 0 · 81 (0 · 70-0 · 94). This population-based case-control study indicates that use of angiotensin II receptor blockers might be associated with a lesser risk of acute pancreatitis, and that the protective association was significant among cases of both severe and mild acute pancreatitis.

  9. The Impact of Type 2 Diabetes on the Efficacy of ADP Receptor Blockers in Patients with Acute ST Elevation Myocardial Infarction: A Pilot Prospective Study

    Directory of Open Access Journals (Sweden)

    Matej Samoš

    2016-01-01

    Full Text Available Background. The aim of this study was to validate the impact of type 2 diabetes (T2D on the platelet reactivity in patients with acute ST elevation myocardial infarction (STEMI treated with adenosine diphosphate (ADP receptor blockers. Methods. A pilot prospective study was performed. Totally 67 patients were enrolled. 21 patients had T2D. Among all study population, 33 patients received clopidogrel and 34 patients received prasugrel. The efficacy of ADP receptor blocker therapy had been tested in two time intervals using light transmission aggregometry with specific inducer and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P flow cytometry assay. Results. There were no significant differences in platelet aggregability among T2D and nondiabetic (ND group. The platelet reactivity index of VASP-P did not differ significantly between T2D and ND group (59.4±30.9% versus 60.0±25.2% and 33.9±25.3% versus 38.6±29.3% in second testing. The number of ADP receptor blocker nonresponders did not differ significantly between T2D and ND patients. The time interval from ADP receptor blocker loading dosing to the blood sampling was similar in T2D and ND patients in both examinations. Conclusion. This prospective study did not confirm the higher platelet reactivity and higher prevalence of ADP receptor blocker nonresponders in T2D acute STEMI patients.

  10. Memory is preserved in older adults taking AT1 receptor blockers.

    Science.gov (United States)

    Ho, Jean K; Nation, Daniel A

    2017-04-26

    Prior work suggests that some but not all antihypertensive treatments may benefit cognition and risk for Alzheimer's disease, independent of stroke. Angiotensin II receptor blockers (ARBs) have been highlighted as one antihypertensive drug class that may confer greatest benefit. The participants comprised 1626 nondemented adults, aged 55-91 years, recruited from Alzheimer's Disease Neuroimaging Initiative sites. Three groups were compared: ARB users (HTN-ARBs), other antihypertensive drug users (HTN-Other), and normotensives. In post hoc analyses, we also examined (1) users of ARBs and angiotensin-converting enzyme inhibitors (ACEIs), (2) users of blood-brain barrier (BBB)-crossing ARBs and users of non-BBB-crossing ARBs, and (3) users of BBB-crossing ARBs and ACEIs (BBB crossers) and users of non-BBB-crossing ARBs and ACEIs (BBB noncrossers). Groups were compared regarding cognition and magnetic resonance imaging measures of brain volume and white matter hyperintensities (WMH), using analysis of covariance and multilevel models. At baseline, the HTN-Other group performed worse than normotensives on Rey Auditory Verbal Learning Test (RAVLT) Immediate Recall (p = 0.002), Delayed Recall (p Memory (p = 0.001), and Trails A (p Memory (p = 0.04) and worse than normotensives on Trails A (p = 0.04). The HTN-Other group performed worse than normotensives on Logical Memory Immediate (p = 0.02) and Delayed Recall over the 3-year follow-up (p = 0.007). Over the follow-up period, those taking BBB-crossing ARBs performed better than the HTN-Other group on AVLT Delayed Recall (p = 0.04), Logical Memory Immediate (p = 0.02), and Delayed Recall (p = 0.05). They also had fewer WMH than the HTN-Other group (p = 0.008) and those taking non-BBB-crossing ARBs (p = 0.05). There were no group differences in brain volume. Users of BBB-crossing medications (ARBs or ACEIs) showed better performance on AVLT Delayed Recall over time than all

  11. Angiotensin Mediated Oxidative Stress and Neuroprotective Potential of Antioxidants and AT1 Receptor Blockers.

    Science.gov (United States)

    Prusty, Shakti Ketan; Sahu, Pratap Kumar; Subudhi, Bharat Bhusan

    2017-01-01

    Oxidative stress in brain underlies the major neurological disorders including Alzheimer's disease (AD) and Parkinson's disease (PD). Peripherally, Angiotensin-II is a major effector of inflammation. Identification of its capacity to access brain during hypertension, as well as location of central renin angiotensin system have led to its recognition as the major effector of oxidative stress in brain. Clinical uses of antioxidants to antagonize this oxidative stress have mostly failed. In this scenario, AT1 blockers have been investigated to prevent neurodegeneration. Although it has shown promise, clinical efficacy is limited to few drugs including telmisartan mainly due to the poor brain availability of others. In this review we aim to analyze the potential of antioxidants to reduce oxidative stress in brain. We have given critical analysis of the approaches for re-purposing of AT1 blockers against oxidative stress induced neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Use of angiotensin II receptor blockers alone and in combination with other drugs: a large clinical experience trial

    Directory of Open Access Journals (Sweden)

    Matthew R Weir

    2001-03-01

    Full Text Available Angiotensin II (Ang II receptor blockers are the newest class of antihypertensive drugs to be developed. No large-scale clinical trials have been performed to evaluate their efficacy alone, or in combination with other drugs. A large-scale, eight week, open-label, non-placebo-controlled, single-arm trial evaluated the efficacy, tolerability and dose-response of candesartan cilexetil, 16—32 mg once-daily, either as monotherapy or as part of combination therapy, in a diverse hypertensive population in actual practice settings. 6465 patients with high blood pressure, of whom 52% were female and 16% African American, with a mean age of 58 years, were included. 5446 patients had essential hypertension and 1014 patients had isolated systolic hypertension. In order to be included in this study, patients had either untreated or uncontrolled hypertension (systolic blood pressure (SBP 140—179 mmHg and/or diastolic blood pressure (DBP 90—109 mmHg inclusive at baseline, despite a variety of other antihypertensive drugs. Of the 5156 patients with essential hypertension and at least one post baseline efficacy measurement, the mean pretreatment blood pressure (BP was 156/97 mmHg. Candesartan cilexetil monotherapy reduced mean SBP/DBP by 18.0/12.2 mmHg. Similarly, in the 964 patients with isolated systolic hypertension and at least one post baseline efficacy measurement, candesartan cilexetil monotherapy reduced SBP/DBP from 158/81 by 16.5/4.5 mmHg. Candesartan cilexetil was similarly effective when employed as add-on therapy. When added to baseline antihypertensive medication in 51% of the patients with essential hypertension not achieving BP control, additional reduction in BP was achieved regardless of the background therapy, including diuretics (17.8/11.7 mmHg calcium antagonists (16.6/11.2 mmHg, beta-blockers (16.5/10.4 mmHg, angiotensin-converting enzyme inhibitors (ACE-I (15.3/10.0 mmHg, and alpha blockers (16.4/10.4 mmHg. Likewise, when

  13. Angiotensin II AT1 receptor blocker candesartan prevents the fast up-regulation of cerebrocortical benzodiazepine-1 receptors induced by acute inflammatory and restraint stress

    Science.gov (United States)

    Sánchez-Lemus, Enrique; Honda, Masaru; Saavedra, Juan M.

    2012-01-01

    Centrally acting Angiotensin II AT1 receptor blockers (ARBs) protect from stress-induced disorders and decrease anxiety in a model of inflammatory stress, the systemic injection of bacterial endotoxin lipopolysaccharide (LPS). In order to better understand the anxiolytic effect of ARBs, we treated rats with LPS (50 µg/kg) with or without three days of pretreatment with the ARB candesartan (1 mg/kg/day), and studied cortical benzodiazepine (BZ) and corticotrophin-releasing factor (CRF) receptors. We compared the cortical BZ and CRF receptors expression pattern induced by LPS with that produced in restraint stress. Inflammation stress produced a generalized increase in cortical BZ1 receptors and reduced mRNA expression of the GABAA receptor γ2 subunit in cingulate cortex; changes were prevented by candesartan pretreatment. Moreover, restraint stress produced similar increases in cortical BZ1 receptor binding, and candesartan prevented these changes. Treatment with candesartan alone increased cortical BZ1 binding, and decreased γ2 subunit mRNA expression in the cingulate cortex. Conversely, we did not find changes in CRF1 receptor expression in any of the cortical areas studied, either after inflammation or restraint stress. Cortical CRF2 receptor binding was undetectable, but CRF2 mRNA expression was decreased by inflammation stress, a change prevented by candesartan. We conclude that stress promotes rapid and widespread changes in cortical BZ1 receptor expression; and that the stress-induced BZ1 receptor expression is under the control of AT1 receptor activity. The results suggest that the anti-anxiety effect of ARBs may be associated with their capacity to regulate stress-induced alterations in cortical BZ1 receptors. PMID:22503782

  14. Unique binding behavior of the recently approved angiotensin II receptor blocker azilsartan compared with that of candesartan.

    Science.gov (United States)

    Miura, Shin-ichiro; Okabe, Atsutoshi; Matsuo, Yoshino; Karnik, Sadashiva S; Saku, Keijiro

    2013-02-01

    The angiotensin II type 1 (AT(1)) receptor blocker (ARB) candesartan strongly reduces blood pressure (BP) in patients with hypertension and has been shown to have cardioprotective effects. A new ARB, azilsartan, was recently approved and has been shown to provide a more potent 24-h sustained antihypertensive effect than candesartan. However, the molecular interactions of azilsartan with the AT(1) receptor that could explain its strong BP-lowering activity are not yet clear. To address this issue, we examined the binding affinities of ARBs for the AT(1) receptor and their inverse agonist activity toward the production of inositol phosphate (IP), and we constructed docking models for the interactions between ARBs and the receptor. Azilsartan, unlike candesartan, has a unique moiety, a 5-oxo-1,2,4-oxadiazole, in place of a tetrazole ring. Although the results regarding the binding affinities of azilsartan and candesartan demonstrated that these ARBs interact with the same sites in the AT(1) receptor (Tyr(113), Lys(199) and Gln(257)), the hydrogen bonding between the oxadiazole of azilsartan-Gln(257) is stronger than that between the tetrazole of candesartan-Gln(257), according to molecular docking models. An examination of the inhibition of IP production by ARBs using constitutively active mutant receptors indicated that inverse agonist activity required azilsartan-Gln(257) interaction and that azilsartan had a stronger interaction with Gln(257) than candesartan. Thus, we speculate that azilsartan has a unique binding behavior to the AT(1) receptor due to its 5-oxo-1,2,4-oxadiazole moiety and induces stronger inverse agonism. This property of azilsartan may underlie its previously demonstrated superior BP-lowering efficacy compared with candesartan and other ARBs.

  15. Effect of Angiotensin receptor blockers on flow-mediated vasodilation: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Chen, Jian-Dong; Liu, Ming; Chen, Xiao-hu; Yang, Zhi-Jian

    2015-01-01

    In a meta-analysis, we investigated the effects of angiotensin receptor blockers (ARBs) in comparison to placebo or other classes of antihypertensive drugs on endothelial function, which was measured by brachial flow-mediated vasodilation (FMD). We searched for randomized controlled trials that compared ARBs with placebo or other classes of antihypertensive drugs in improving FMD. A random-effect model was used to compute pooled estimates. In 13 trials (n = 529), ARBs were more efficacious in improving brachial FMD than placebo [pooled weighted mean change difference (WMD) 1.34%, 95% CI, 0.93-1.75%, pclasses of drugs (p ≥ 0.072). This meta-analysis shows that ARBs improve brachial FMD, a marker of endothelial function, and that they are superior to placebo and CCBs. There was no significant difference in the effect on brachial FMD between ARBs and the other antihypertensive drugs. © 2015 S. Karger AG, Basel.

  16. Dosage of angiotensin-II receptor blockers in heart failure patients following changes in Danish drug reimbursement policies

    DEFF Research Database (Denmark)

    Selmer, Christian; Lamberts, Morten; Kristensen, Søren Lund

    2014-01-01

    PURPOSE: National reimbursement policies in Denmark were changed in November 2010 favouring a shift in angiotensin-II receptor blocker (ARB) treatment to generic losartan for heart failure (HF) patients. We examined how changes in reimbursement policies affected the fraction of HF patients up-titrated...... to optimal or suboptimal ARB dosage. METHODS: A historical cohort study was performed including HF patients with at least one prescription of ARB in the months of May-Jul 2010 (baseline). Patients were considered up-titrated at doses 100, 16 or 160 mg for losartan, valsartan and candesartan, respectively....... Individual-level linkage of nationwide registries of hospitalization and drug dispensing in Denmark was used to describe patterns of ARB prescriptions and estimate dosage before and after November 2010. Logistic regression models were used to assess the probability for being up-titrated in the period...

  17. Angiotensin receptor blocker as adjunctive therapy for rhythm control in atrial fibrillation: results of the irbesartan-amiodarone trial.

    Science.gov (United States)

    Madrid, Antonio H; Escobar, Carlos; Rebollo, José María G; Marín, Irene; Bernal, Enrique; Nannini, Sebastián; Limón, Lilianna; Peng, Jian; Moro, Concepción

    2003-09-01

    Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of stroke and mortality. The early appearance of electrical remodeling is followed by structural remodeling of the atrial tissue. Direct current cardioversion of persistent AF is the most effective treatment for the restoration of sinus rhythm, but it is hampered by a high percentage of recurrences. Recurrences may be the consequence of both electrical and structural remodeling. A study on the use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent AF showed that this angiotensin II receptor blocker combined with amiodarone prolonged sinus rhythm after cardioversion. Irbesartan may have antifibrotic effects due not only to the ability to diminish the synthesis of collagen type I molecules but also to its capacity to stimulate the degradation of collagen type I fibers, as has been demonstrated with losartan, another angiotensin II receptor blocker. This suggests that efforts to reduce the structural changes that occur during AF may be more useful in preventing recurrences than efforts designed to minimize the electrical changes alone. The AFFIRM trial compared two approaches to the treatment of AF: cardioversion with antiarrhythmic drugs to maintain sinus rhythm and the use of rate-controlling drugs. The results show that management of AF with the rhythm-control strategy offers no survival advantage over the rate-control strategy. However, non-antiarrhythmic drugs to prevent recurrences, like irbesartan, were not controlled and amiodarone was used in a low percentage of the patients. The treatment strategies proposed in both AFFIRM and RACE, in our opinion, may not be the optimal. The modern clinical approach to AF involves an early intervention to restore sinus rhythm, therefore preventing atrial remodeling. The pretreatment of patients with AF who undergo electrical cardioversion is very important and will be the subject for continuous improvement.

  18. 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. The ...... of single markers to establish drug efficacy....

  19. Beta Blockers

    Science.gov (United States)

    Beta blockers Beta blockers, also called beta-adrenergic blocking agents, treat a variety of conditions, such as high blood pressure and migraines. ... this class of medication. By Mayo Clinic Staff Beta blockers, also known as beta-adrenergic blocking agents, are ...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. Abilities of candesartan and other AT1 receptor blockers to impair angiotensin II-induced AT1 receptor activation after wash-out

    Science.gov (United States)

    Kiya, Yoshihiro; Miura, Shin-ichiro; Matsuo, Yoshino; Karnik, Sadashiva S; Saku, Keijiro

    2013-01-01

    Angiotensin II (Ang II) binds to Ang II type 1 (AT1) receptor and evokes cell signaling, and subsequently stimulates vasoconstriction and cell proliferation, which eventually lead to cardiovascular disease. Since most AT1 receptor blockers (ARBs) have molecular (differential) effects, we evaluated the specific features of candesartan and compared the abilities of candesartan and other ARBs (olmesartan, telmisartan, valsartan, irbesartan and losartan) to bind to and activate AT1 receptors using a cell-based wash-out assay. Each ARB blocked Ang II-induced extracellular signal-regulated kinase (ERK) activation and inositol phosphate production to different degrees after wash-out. In addition, a small difference in the molecular structure, i.e. a carboxyl group, between candesartan and candesartan-7H was associated with a difference in the degree of this blocking effect. In addition, interaction between Gln257 in the AT1 receptor and the carboxyl group of candesartan may be partially associated with the effect of candesartan after wash-out. Although our findings regarding the molecular effects of ARB are based on basic research, these findings may lead to an exciting new area in the clinical application of ARBs. PMID:21824992

  5. Abilities of candesartan and other AT(1) receptor blockers to impair angiotensin II-induced AT(1) receptor activation after wash-out.

    Science.gov (United States)

    Kiya, Yoshihiro; Miura, Shin-ichiro; Matsuo, Yoshino; Karnik, Sadashiva S; Saku, Keijiro

    2012-03-01

    Angiotensin II (Ang II) binds to Ang II type 1 (AT(1)) receptor and evokes cell signaling, and subsequently stimulates vasoconstriction and cell proliferation, which eventually lead to cardiovascular disease. Since most AT(1) receptor blockers (ARBs) have molecular (differential) effects, we evaluated the specific features of candesartan and compared the abilities of candesartan and other ARBs (olmesartan, telmisartan, valsartan, irbesartan and losartan) to bind to and activate AT(1) receptors using a cell-based wash-out assay. Each ARB blocked Ang II-induced extracellular signal-regulated kinase (ERK) activation and inositol phosphate production to different degrees after wash-out. In addition, a small difference in the molecular structure, i.e. a carboxyl group, between candesartan and candesartan-7H was associated with a difference in the degree of this blocking effect. In addition, interaction between Gln(257) in the AT(1) receptor and the carboxyl group of candesartan may be partially associated with the effect of candesartan after wash-out. Although our findings regarding the molecular effects of ARB are based on basic research, these findings may lead to an exciting new area in the clinical application of ARBs.

  6. Use of angiotensin II receptor blockers in children- a review of ...

    African Journals Online (AJOL)

    2015-05-19

    May 19, 2015 ... teinuria in renal disease. Safety pharmacokinetic, dosage, and palatability of adult formulations for the paediatric age group are highlighted. Conclusion: Angiotensin receptor antagonists are useful effective and safe alternatives to available antihypertensive therapy in paedi- atric population. Angiotensin re-.

  7. Time-resolved photolabeling by the noncompetitive blocker chlorpromazine of the acetylcholine receptor in its transiently open and closed ion channel conformations.

    OpenAIRE

    Heidmann, T; Changeux, J P

    1984-01-01

    A rapid-mixing photolabeling apparatus is developed to resolve the kinetics of association of the noncompetitive channel blocker [3H]chlorpromazine (CPZ) with the membrane-bound acetylcholine (AcCho) receptor from Torpedo marmorata and to photolabel its subunits in the 100-milli-seconds to seconds time range. Rapid mixing of AcCho and [3H]CPZ with the receptor followed by brief (less than 20 msec) UV irradiation results in the selective labeling of the four chains of the AcCho receptor, accor...

  8. Effect of angiotensin II type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Ik Soo Byon

    2017-06-01

    Full Text Available AIM: To investigate the effect of angiotensin II type 1 receptor blocker (ARB and angiotensin converting enzyme inhibitor (ACEI on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS: Forty Sprague-Dawley rats were divided into 4 groups: control, diabetes mellitus (DM, candesartan-treated DM, and enalapril-treated DM (each group, n=10. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/(kg·d] and enalapril [ACEI, 10 mg/(kg·d] were administered to rats orally for 4wk. Vascular endothelial growth factor (VEGF and angiotensin II (Ang II concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor (AT1R levels were assessed at week 4 by Western blotting. RESULTS: Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control (P=0.04 and 0.005, respectively. Vitreous AT1R increased significantly in DM compared to the other three groups (P<0.007. Candesartan-treated DM rats showed higher vitreal AT1R concentration than the enalapril-treated DM group and control (P<0.001 and P=0.005, respectively. No difference in vitreous Ang II and AT1R concentration was found between the enalapril-treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION: Increased Ang II and AT1R in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

  9. AT1 receptor blocker losartan protects against mechanical ventilation-induced diaphragmatic dysfunction

    Science.gov (United States)

    Kwon, Oh Sung; Smuder, Ashley J.; Wiggs, Michael P.; Hall, Stephanie E.; Sollanek, Kurt J.; Morton, Aaron B.; Talbert, Erin E.; Toklu, Hale Z.; Tumer, Nihal

    2015-01-01

    Mechanical ventilation is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged ventilator support results in diaphragmatic atrophy and contractile dysfunction leading to diaphragm weakness, which is predicted to contribute to problems in weaning patients from the ventilator. While it is established that ventilator-induced oxidative stress is required for the development of ventilator-induced diaphragm weakness, the signaling pathway(s) that trigger oxidant production remain unknown. However, recent evidence reveals that increased plasma levels of angiotensin II (ANG II) result in oxidative stress and atrophy in limb skeletal muscles. Using a well-established animal model of mechanical ventilation, we tested the hypothesis that increased circulating levels of ANG II are required for both ventilator-induced diaphragmatic oxidative stress and diaphragm weakness. Cause and effect was determined by administering an angiotensin-converting enzyme inhibitor (enalapril) to prevent ventilator-induced increases in plasma ANG II levels, and the ANG II type 1 receptor antagonist (losartan) was provided to prevent the activation of ANG II type 1 receptors. Enalapril prevented the increase in plasma ANG II levels but did not protect against ventilator-induced diaphragmatic oxidative stress or diaphragm weakness. In contrast, losartan attenuated both ventilator-induced oxidative stress and diaphragm weakness. These findings indicate that circulating ANG II is not essential for the development of ventilator-induced diaphragm weakness but that activation of ANG II type 1 receptors appears to be a requirement for ventilator-induced diaphragm weakness. Importantly, these experiments provide the first evidence that the Food and Drug Administration-approved drug losartan may have clinical benefits to protect against ventilator-induced diaphragm weakness in humans. PMID:26359481

  10. The Effect of an Angiotensin Receptor Blocker on Arterial Stiffness in Type 2 Diabetes Mellitus Patients with Hypertension

    Directory of Open Access Journals (Sweden)

    Ji Hyun Kim

    2011-06-01

    Full Text Available BackgroundHypertension and type 2 diabetes mellitus are major risk factors for cardiovascular disease. This study analyzed the changes in central aortic waveforms and pulse wave velocity as well as related parameters after treatment with valsartan, an angiotensin II type 1 receptor blocker, in patients with type 2 diabetes and hypertension.MethodsWe used pulse wave analysis to measure central aortic waveform in a total of 98 subjects. In 47 of these patients, pulse wave velocity measurements were obtained before and after 12 weeks of treatment with valsartan.ResultsIn the central aortic waveform analysis, the aortic pulse pressure and augmentation index were significantly decreased after valsartan treatment, as was the aortic pulse wave velocity. Factors contributing to the improvement in pulse wave velocity were the fasting blood glucose and haemoglobin A1c levels.ConclusionShort-term treatment with valsartan improves arterial stiffness in patients with type 2 diabetes and hypertension, and the glucose status at baseline was associated with this effect.

  11. Switch strategies in the management of hypertension: a cost minimisation analysis of angiotensin receptor blocker based regimen.

    Science.gov (United States)

    Belsey, J D

    2008-02-01

    Budgetary pressures within health care systems have led many health care providers to consider the switching of patients on long term anti hypertensive medication to agents with the lowest acquisition price. The long term success of this strategy hinges on price differentials remaining stable, an assumption that may not be valid in drug classes where patent expiry times vary. The treatment of hypertension using angiotensin receptor blockers (ARBs) represents just such a case. The present study, therefore, modelled the 5-year cost consequences of treatment based on losartan, candesartan, valsartan and irbesartan, based on expected patent expiry dates. A Markov model was constructed, applying dose-specific blood-pressure lowering and costs to a cohort of uncontrolled mild-moderate hypertensive patients and assessing the anticipated cost of treatment over a 5 year period. A probabilistic approach was adopted to account for between-patient and between-treatment differences. For both undiscounted and discounted models, a losartan-based regimen represents the least costly option of the four agents tested. Median (IQR) discounted expenditure per patient for each agent was: losartan: pound 506 ( pound 441- pound 650), candesartan: pound 610 ( pound 542- pound 766), valsartan: pound 809 ( pound 796- pound 1078), irbesartan pound 696 ( pound 694- pound 934). Switching hypertensive patients taking ARBs to the agent with the lowest current acquisition cost may yield only transient budgetary savings. Once patent expiry is taken into account, this model suggests that maintaining or switching patients to losartan would yield considerably greater savings over 5 years.

  12. Effects of the AT1 receptor blocker candesartan on myocardial ischemia/reperfusion in isolated rat hearts.

    Science.gov (United States)

    Songur, C Murat; Songur, Merve Ozenen; Kocabeyoglu, Sinan Sabit; Basgut, Bilgen

    2014-10-01

    We sought to investigate the effects of the angiotension II receptor blocker candesartan on ischemia-reperfusion injury using a cardioplegia arrested isolated rat heart model. Ischemia-reperfusion injury was induced in isolated rat hearts with 40 minutes of global ischemia followed by a 30-minute reperfusion protocol. Throughout the experiment, constant pressure perfusion was achieved using a Langendorff apparatus. Cardioplegic solution alone, and in combination with candesartan, was administered before ischemia and 20 minutes after ischemia. Post-ischemic recovery of contractile function, left ventricular developed pressure, left ventricular end-diastolic pressure and contraction and relaxation rates were evaluated. In the control group, left ventricular developed pressure, rate pressure product, contraction and relaxation rates and coronary flow significantly decreased but coronary resistance increased following reperfusion. With the administration of candesartan alone, parameters did not differ compared to controls. Contractile parameters improved in the group that received candesartan in combination with the cardioplegia compared to the group that received cardioplegia alone; however, the difference between these two groups was insignificant. In this study, the addition of candesartan to a cardioplegic arrest protocol routinely performed during cardiac surgery did not provide a significant advantage in protection against ischemia-reperfusion injury compared with the administration of cardioplegic solution alone.

  13. Regression of atherosclerosis in apolipoprotein E-deficient mice is feasible using high-dose angiotensin receptor blocker, candesartan.

    Science.gov (United States)

    Hayashi, Kaori; Sasamura, Hiroyuki; Azegami, Tatsuhiko; Itoh, Hiroshi

    2012-01-01

    Clinical studies have suggested that renin-angiotensin inhibitors are effective for the prevention of atherosclerosis progression, but the results for the regression of established lesions are equivocal. The aim of this study was to examine the effects of different doses of the angiotensin receptor blocker (ARB) candesartan on the regression of atherosclerosis and lipid-induced nephropathy in apolipoprotein E (apoE)-deficient spontaneously hyperlipidemic (SHL) mice. Male SHL were given an atherogenic diet together with salt loading to induce atherosclerosis. The mice were then treated with various doses of candesartan (0-50 mg/kg/d) for 12 weeks. Treatment with high-dose candesartan caused clear regression of atherosclerotic plaques in the aorta, which was not observed with normal-dose candesartan. Biglycan and ACAT1 expression were significantly decreased, and aortic free cholesterol: cholesterol ester ratios were increased in these mice. Treatment of cultured THP-1 macrophages in vitro with candesartan resulted in a similar decrease in ACAT1 expression. In the kidney, glomerular lipid accumulation, mesangial expansion, and albuminuria were significantly regressed after treatment with high-dose candesartan, while biglycan and ACAT1 expressions were decreased. These results suggest that regression of established atherosclerosis lesions in ApoE-deficient mice is feasible using high-dose candesartan, by mechanisms involving (i) a decrease in the lipid-retaining proteoglycan biglycan, and (ii) suppression of ACAT1 expression resulting in increased free cholesterol for lipid release.

  14. Effect of angiotensin II receptor blockers, candesartan, on osteoprotegerin level in hypertensive patients: Link between bone and RAAS.

    Science.gov (United States)

    Oz, H; Gavish, D; Hass, A; Shargorodsky, M

    2015-09-01

    The renin-angiotensin-aldosterone system (RAAS) has recently been considered as a possible link between bone and vascular disease. The present study was designed to determine the effect of the angiotensin II receptor blocker candesartan on circulating osteoprotegerin (OPG) in hypertensive patients with multiple cardiovascular risk factors. A total of 69 hypertensive patients were randomized to two groups: Group 1 included patients treated with oral candesartan in doses of 16 mg to 32 mg per day in addition to routine standard of care (routine care + ARB), and Group 2 included patients who received routine standard of care other than ARBs or ACEIs, with no change to their treatment (routine care). Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, CRP, aldosterone, renin, homeostasis model assessment-insulin resistance (HOMA-IR) and OPG. Baseline OPG levels did not differ significantly by treatment group. Post-treatment serum OPG levels were marginally lower in Group1 compared with Group 2; however, this decrease did not reach statistical significance (p = 0.077). In the present study, treatment with the ARB candesartan had no significant effect on circulating OPG levels in hypertensive patients with multiple cardiovascular risk factors. To the best of our knowledge, the present study is the first to estimate an effect of candesartan on bone remodeling marker such as OPG. © The Author(s) 2015.

  15. Cardioprotective effect of fimasartan, a new angiotensin receptor blocker, in a porcine model of acute myocardial infarction.

    Science.gov (United States)

    Sim, Doo Sun; Jeong, Myung Ho; Song, Ho Chun; Kim, Jahae; Chong, Ari; Bom, Hee Seung; Jeong, In Seok; Oh, Sang Gi; Kim, Jong Min; Park, Dae Sung; Kim, Jung Ha; Lim, Kyung Seob; Kim, Min Suk; Ryu, Shi Hyun; Kim, Hyun Kuk; Kim, Sung Soo; Jang, Su Young; Cho, Jae Yeong; Jeong, Hae Chang; Lee, Ki Hong; Park, Keun Ho; Yoon, Nam Sik; Yoon, Hyun Ju; Kim, Kye Hun; Hong, Young Joon; Park, Hyung Wook; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

    2015-01-01

    Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

  16. Randomised trial on episodic cluster headache with an angiotensin II receptor blocker

    DEFF Research Database (Denmark)

    Tronvik, Erling; Wienecke, Troels; Monstad, Inge

    2013-01-01

    OBJECTIVES: The aim of this study was to evaluate the angiotensin II receptor antagonist candesartan as prophylactic medication in patients with episodic cluster headache. METHODS: This study comprised a prospective, placebo-controlled, double-blind, parallel-designed trial performed in seven...... the candesartan and placebo group was not significant with the pre-planned non-parametric ranking test, but a post-hoc exact Poisson test, which takes into account the temporal properties of the data, revealed a significant result ( P  ...

  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. Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood-Brain Barrier Disruption after Experimental Stroke in Mice.

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    Emil Zeynalov

    Full Text Available Stroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB disruption, and is often accompanied by increased release of arginine-vasopressin (AVP. AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP receptor blockers conivaptan (V1a and V2 and tolvaptan (V2 are used to correct hyponatremia, but their effect on post-ischemic brain edema and BBB disruption remains to be elucidated. Therefore, we conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke.Experimental mice underwent the filament model of middle cerebral artery occlusion (MCAO with reperfusion. Mice were treated with conivaptan, tolvaptan, or vehicle. Treatments were initiated immediately at reperfusion and administered IV (conivaptan or orally (tolvaptan for 48 hours. Physiological variables, neurological deficit scores (NDS, plasma and urine sodium and osmolality were recorded. Brain water content (BWC and Evans Blue (EB extravasation index were evaluated at the end point.Both conivaptan and tolvaptan produced aquaresis as indicated by changes in plasma and urine sodium levels. However plasma and urine osmolality was changed only by conivaptan. Unlike tolvaptan, conivaptan improved NDS and reduced BWC in the ipsilateral hemisphere: from 81.66 ± 0.43% (vehicle to 78.28 ± 0.48% (conivaptan, 0.2 mg, p < 0.05 vs vehicle. Conivaptan also attenuated the EB extravasation from 1.22 ± 0.08 (vehicle to 1.01 ± 0.02 (conivaptan, 0.2 mg, p < 0.05.Continuous IV infusion with conivaptan for 48 hours after experimental stroke reduces brain edema, and BBB disruption. Conivaptan but not tolvaptan may potentially be used in patients to prevent brain edema after stroke.

  19. ANGIOTENSIN CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS: IS THERE A REASON TO CONSIDER AN EQUIVALENCE OF TWO DRUG CLASSES FROM THE EVIDENCE BASED MEDICINE STANDPOINT

    Directory of Open Access Journals (Sweden)

    S. Yu. Martsevich

    2013-01-01

    Full Text Available The results of the main large controlled trials that had proven effect of ACE inhibitors (ACEi and angiotensin receptor blockers (ARB on cardiovascular diseases outcomes are evaluated. Data of the recent meta-analyzes comparing ACEi and ARB effects on the life prognosis in patients of the high cardiovascular risk are presented. Better validity of ACEi efficacy versus this of ARB is concluded.

  20. Structure-Function Basis of Attenuated Inverse Agonism of Angiotensin II Type 1 Receptor Blockers for Active-State Angiotensin II Type 1 Receptor.

    Science.gov (United States)

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

    2015-09-01

    Ligand-independent signaling by the angiotensin II type 1 receptor (AT1R) can be activated in clinical settings by mechanical stretch and autoantibodies as well as receptor mutations. Transition of the AT1R to the activated state is known to lower inverse agonistic efficacy of clinically used AT1R blockers (ARBs). The structure-function basis for reduced efficacy of inverse agonists is a fundamental aspect that has been understudied not only in relation to the AT1R but also regarding other homologous receptors. Here, we demonstrate that the active-state transition in the AT1R indeed attenuates an inverse agonistic effect of four biphenyl-tetrazole ARBs through changes in specific ligand-receptor interactions. In the ground state, tight interactions of four ARBs with a set of residues (Ser109(TM3), Phe182(ECL2), Gln257(TM6), Tyr292(TM7), and Asn295(TM7)) results in potent inverse agonism. In the activated state, the ARB-AT1R interactions shift to a different set of residues (Val108(TM3), Ser109(TM3), Ala163(TM4), Phe182(ECL2), Lys199(TM5), Tyr292(TM7), and Asn295(TM7)), resulting in attenuated inverse agonism. Interestingly, V108I, A163T, N295A, and F182A mutations in the activated state of the AT1R shift the functional response to the ARB binding toward agonism, but in the ground state the same mutations cause inverse agonism. Our data show that the second extracellular loop is an important regulator of the functional states of the AT1R. Our findings suggest that the quest for discovering novel ARBs, and improving current ARBs, fundamentally depends on the knowledge of the unique sets of residues that mediate inverse agonistic potency in the two states of the AT1R. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  1. [Comparison of effects of systemic (intramuscular) and intrastriatal injections of D1-dopamine receptor blocker on motor behavior and postural adjustment in dogs].

    Science.gov (United States)

    Shapovalova, K B; Kamkina, Iu V

    2008-01-01

    The study is based on the concept (Shapovalova, 2000) that activation and blockade of various types of muscarine and dopamine receptors located at various outputs of neostriatum should have different effects on motor behavior. The goal of the study was comparison of effects of systemic and intrastriatal injections of a selective blocker of D1 dopamine receptors on motor behavior. Experiments were carried out on 5 dogs on a model of instrumental defensive reflex (IDR) connected with keeping a certain flexor posture. Performance of the experiments, recording, storage, and analysis of data were accomplished with aid of original programs for PC. Systemic (intramuscular) administration of the blocker of D1 dopamine receptors SCH23390 at a dose of 0.025 mg/kg led to a sharp decrease of the IDR amplitude and in most cases--to the complete refusal of its performance. First of all, the phasic component of the instrumental response was inhibited, the diagonal pattern of the postural adjustment being preserved. Bilateral microinjections into the dog neostriatum of the same blocker of D1 receptors at a dose of 0.1 and 1.0 g did not change the percent of correct solution of the instrumental task, but at the same time produced a great number of changes in motorics: latent period of response increased statistically significantly, in some cases its amplitude rose, phasity decreased, intersignal raisings of limbs ceased completely. The obtained data allow the following conclusions to be made. 1. Difference of effects of systemic and intrastriatal injections of SCH23390 seems to be due to that at its systemic administration, D1 receptors of other structures, not only of neostriatum, can also be blocked. 2. Effect of nigrostriatal dopaminergic system on neostriatum via D1 receptors is complex - activation of motor activity (projectional spine neurons of the direct pathway) and a weak modulation of mental process (large spineless cholinergic interneurons). 3. Regulation of movement

  2. 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.

  3. Impact of ACE inhibitors and AII receptor blockers on peritoneal membrane transport characteristics in long-term peritoneal dialysis patients.

    Science.gov (United States)

    Kolesnyk, Inna; Dekker, Friedo W; Noordzij, Marlies; le Cessie, Saskia; Struijk, Dirk G; Krediet, Raymond T

    2007-01-01

    Long-term peritoneal dialysis (PD) may lead to peritoneal fibrosis and ultrafiltration failure. The latter occurs due to high solute transport rates and diabetiform peritoneal sclerosis. Angiotensin-II (AII) is known to be a growth factor in the development of fibrosis and a number of animal studies have shown it likely that inhibiting the effects of AII by angiotensin-converting enzyme (ACE) or angiotensin receptor blocker (ARB) will attenuate these complications. To investigate the effects of ACE/AII inhibitors in long-term PD patients. We analyzed data from 66 patients treated with PD therapy at our center for at least 2 years, during which time at least 2 standard peritoneal permeability analyses (SPAs) were performed. 36 patients were treated with ACE/AII inhibitors (ACE/ARB group); the other 30 received none of the above drugs during the entire follow-up (control group). The two groups were compared with respect to changes in peritoneal transport over the follow-up time. A significant difference in time course of peritoneal transport was found between the 2 groups: in the ACE/ARB group, small solute transport had decreased, while it had increased in the control group. This finding was confirmed by analysis using mixed model for repeated measures. The value of mass transfer area coefficient of creatinine was influenced by the duration of PD therapy (p = 0.017) and this interaction was different with respect to use of ACE/AII inhibitors (p = 0.037). The trend was not found in protein clearances or fluid kinetics. Our findings suggest that ACE/AII inhibition is likely to prevent the increase in mass transfer area coefficients that occurs in long-term PD, which is in line with results of experimental animal studies.

  4. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers reduced dementia risk in patients with diabetes mellitus and hypertension.

    Science.gov (United States)

    Kuan, Yi-Chun; Huang, Kuang-Wei; Yen, Der-Jen; Hu, Chaur-Jong; Lin, Cheng-Li; Kao, Chia-Hung

    2016-10-01

    The effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) on dementia risk in patients with type 2 diabetes mellitus (DM) and hypertension remain unknown. We investigated the effects of ACEIs and ARBs on dementia risk in patients with type 2 DM and hypertension. We conducted a cohort study by using the Taiwan National Health Insurance Research Database. We included 2377 patients receiving ACEIs and 1780 patients receiving ARBs in the ACEI and ARB cohorts, respectively. We included a comparable number of patients not receiving ACEIs and ARBs as controls in the non-ACEI and non-ARB cohorts through propensity score matching. The effect of ACEIs and ARBs on dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors. During the 12-year follow-up period, compared with the non-ACEI cohort, all-cause dementia risk decreased by 26% in the ACEI cohort [hazard ratio (HR)=0.74, 95% confidence interval (CI)=0.56-0.96]. The all-cause dementia risk was nearly 40% lower in the ARB cohort than in the non-ARB cohort (HR=0.60, 95% CI=0.37-0.97). These drugs prevented the occurrence of vascular dementia (VD), however, this effect was nonsignificant for Alzheimer's dementia (AD). Treatment duration- and dosage-related protection effects on dementia occurrence were observed. ACEIs and ARBs may effectively prevent all-cause dementia, particularly VD, in patients with type 2 DM and hypertension. Moreover, compared with ACEIs, ARBs appear to be more advantageous in dementia prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Evaluation of the effect of angiotensin converting enzyme inhibitors and angiotensin receptors blockers on aspirin antiplatelet effect.

    Science.gov (United States)

    Al-Azzam, Sayer I; Alzoubi, Karem H; Khabour, Omar F; Quttina, Maram; Zayadeen, Raya

    2016-02-01

    Cardiovascular disease (CVD) is one of the major burdens on societies and healthcare systems. Antiplatelet aspirin is used to prevent the occurrence or reoccurrence of cardiovascular events. However, studies have shown that a good portion of patients still suffer from cardiovascular events in spite of using aspirin (also called aspirin nonresponders). On the other hand, angiotensin-converting enzyme inhibitors (ACEIs) as well as angiotensin-receptor blockers (ARBs) are widely used in patients with different spectrums of cardiovascular diseases. In this study, the possible interactive effect of ACEIs and ARBs on aspirin response was evaluated in vitro. A multiplate analyzer was used to assay the possible interactions between ACEIs and ARBs drugs on antiplatelet effect of aspirin using blood obtained from 6 healthy volunteers. Means of area under the aggregation curves (AUCs) of the blood samples treated with 10 μg/mL aspirin were calculated before and after exposure to captopril, lisinopril, candesartan, or losartan. Results showed potential antithrombotic effect of ACEIs and ARBs only at high concentrations (3.3 μg/mL).The antiplatelet effect of aspirin 10 μg/mL was significantly enhanced by the addition of captopril or lisinopril at high dose (3.3 μg/mL), candesartan at all tested doses (0.03 μg/mL, 0.33 μg/mL, 3.3 μg/mL), and losartan at doses of 0.33 μg/mL and 3.3 μg/m. Treatment with ACEIs (captopril and lisinopril) and ARBs (candesartan and losartan) improved the antiplatelet response to aspirin. Further studies are needed to confirm this action and potentially apply it to clinical practice.

  6. Reduction of amiodarone pulmonary toxicity in patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

    Science.gov (United States)

    Kosseifi, Semaan G; Halawa, Ahmad; Halawa, Ahmed; Bailey, Beth; Micklewright, Melinda; Roy, Thomas M; Byrd, Ryland P

    2009-12-01

    Amiodarone (AM) is a widely used anti-arrhythmic medication. Its utility is, however, limited by adverse side effects. The mechanism of amiodarone-induced toxicity (APT) in the lungs is attributed primarily to stimulation of the angiotensin enzyme system leading to lung cell apoptosis and cell death. This mechanism has been demonstrated by in vitro and in vivo experimental animal studies. To date, however, no in vivo human studies have confirmed this mechanism for APT. This study was undertaken to determine whether angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) offer a protective effect against APT in humans. Demonstration of a protective effect of an ACE-I or ARB would suggest that stimulation of the angiotensin enzyme system may be a key process in APT. An 8-year retrospective analysis of all patients on AM therapy at the James H. Quillen Veterans Affairs Medical Center was undertaken. A total of 1000 patients on AM were identified. One-hundred-and-seventeen were excluded from the study. Five-hundred-and-twenty-four patients were simultaneously on an ACE-I or ARB. The remaining 359 patients were not. Pulmonary toxicity attributed to AM was identified in five and 14 patients with and without concomitant ACE-I or ARB therapy, respectively. The APT rate for the entire patient sample was 2.2%. APT occurred in 1% of patients on an ACE-I or ARB and in 3.9% of patients not taking an ACE-I or ARB. This observed difference in percentage of APT was statistically significant. The concomitant use of ACE-I or ARB in patients taking AM appears to offer a protective effect against APT. This observation suggests that the stimulation of the angiotensin enzyme system may play an important role in APT in humans.

  7. 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.

  8. 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.

  9. Angiotensin II Receptor Blockers

    Science.gov (United States)

    ... a chemical in your body that affects your cardiovascular system in various ways, including narrowing your blood vessels. This narrowing can increase your blood pressure and force your heart to work harder. Angiotensin ...

  10. αIIbβ3-integrin Ligands: Abciximab and Eptifibatide as Proapoptotic Factors in MCF-7 Human Breast Cancer Cells.

    Science.gov (United States)

    Kononczuk, Joanna; Surazynski, Arkadiusz; Czyzewska, Urszula; Prokop, Izabela; Tomczyk, Michal; Palka, Jerzy; Miltyk, Wojciech

    2015-01-01

    Integrin receptors are considered to be the key factors in carcinogenesis. αIIbβ3-Integrin (GP IIb/IIIa) is the main glycoprotein of the surface of platelets, its presence has also been noted on the certain cancer cell lines. The molecular mechanism of its action in cancer cells remains unknown. This study presents effects of two αIIbβ3-inhibitors: Abciximab and Eptifibatide on apoptosis, expression of proline oxidase (POX), signaling molecules ERK 1/2, transcription factor NF-κB and HIF-1α, vascular endothelial growth factor (VEGF) as well as DNA biosynthesis, collagen biosynthesis and prolidase activity in MCF-7 breast cancer cells. Both ligands induced apoptosis, however we found significant differences in molecular mechanism of action between tested αIIbβ3-inhibitors. These differences include expression of POX, HIF-1α, NF-κB,VEGF and collagen biosynthesis. Eptifibatide presented stronger proapoptotic activity in MCF-7 cells than Abciximab. Results of this study suggest that Eptifibatide may be considered as a novel candidate for development of new anticancer therapy.

  11. Lack of an association between angiotensin receptor blocker based therapy and increased risk of cancer: evidence from large observational studies.

    Science.gov (United States)

    Yang, Yuan; Zhang, Fan; Skrip, Laura; Lei, Han; Luo, Suxin; Lu, Kai; Hu, Dayi

    2015-01-01

    A previous meta-analysis of randomized controlled studies that were not designed to investigate cancer as a primary outcome suggested that ARB-based therapy is associated with increased risk of cancer; however, results of recent observational studies considering the association have been contradictory. This study sought to evaluate the association between angiotensin receptor blocker (ARB)-based therapy and risk of cancer by conducting a meta-analysis of observational studies. Relevant articles published before February 2014 were identified by searching PubMed and the Cochrane Library. Pooled relative risks (RRs) were determined using a random effects model and were used to assess the strength of association between use of ARB-based therapy and risk of cancer. Six retrospective cohort studies involving a total of 3,827,109 participants and four case-control studies involving a total of 193,029 cases were included. The present study found that ARB-based therapy was not significantly associated with an increased risk of cancer (RR = 0.87, 95%CI: [0.75, 1.01]). However, an analysis including only cohort studies suggested a significantly decreased risk of cancer among individuals with any history of ARB use as compared to those with no history of ARB use (RR = 0.80, 95%CI: [0.55, 0.95]); no significant association was found between ARB use and risk of cancer when the case-control studies were separately considered (RR = 1.03, 95%CI: [0.93, 1.13]). Subgroup analyses showed that use of ARB-based therapy was associated with decreased risk of lung cancer (RR = 0.81, 95%CI: [0.69, 0.94]); however, no significant associations were found with the other cancer sites investigated. Furthermore, no association was observed upon adjustment by type of ARB drug. No publication bias was detected. Overall, ARB-based therapy was not associated with increased risk of cancer. However, its use may be related to decreased incidence of lung cancer; this finding should be considered

  12. The angiotensin II type 1 receptor blocker losartan attenuates bioprosthetic valve leaflet calcification in a rabbit intravascular implant model.

    Science.gov (United States)

    Shin, Hong Ju; Kim, Dae-Hyun; Park, Han Ki; Park, Young Hwan

    2016-12-01

    There is evidence that angiotensin II type I receptor blocker (ARB) could reduce structural valve deterioration. However, the anticalcification effect on the bioprosthetic heart valve (BHV) has not been investigated. Thus, we investigated the effects of losartan (an ARB) on calcification of implanted bovine pericardial tissue in a rabbit intravascular implant model. A total of 16 male New Zealand White rabbits (20 weeks old, 2.98-3.34 kg) were used in this study. Commercially available BHV leaflet of bovine pericardium was trimmed to the shape of a 3-mm triangle and implanted to both external jugular veins of the rabbit. The ARB group (n = 8) was given 25 mg/kg of powdered losartan daily until 6 weeks after surgery by direct administration in the buccal pouch of the animals. The control group (n = 8) was given 5 ml of normal saline by the same method. After 6 weeks, quantitative calcium determination, histological evaluation and western blot analysis of interleukin-6 (IL-6), osteopontin and bone morphogenetic protein 2 (BMP-2) were performed to investigate the mechanisms of the anticalcification effect of losartan. No deaths or complications such as infection or haematoma were recorded during the experiment. All animals were euthanized on the planned date. The calcium measurement level in the ARB group (2.28 ± 0.65 mg/g) was significantly lower than that in the control group (3.68 ± 1.00 mg/g) (P = 0.0092). Immunohistochemistry analyses revealed that BMP-2-positive reactions were significantly attenuated in the ARB group. Western blot analysis showed that losartan suppressed the expression of IL-6, osteopontin and BMP-2. Our results indicate that losartan significantly attenuates postimplant degenerative calcification of a bovine pericardial bioprosthesis in a rabbit intravascular implant model. Further studies are required to assess the effects of ARBs on BHV tissue in orthotopic implantations using a large animal model. © The Author 2016. Published by Oxford

  13. Severe hepatic encephalopathy in a patient with liver cirrhosis after administration of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy: a case report

    Directory of Open Access Journals (Sweden)

    Podda Mauro

    2010-05-01

    Full Text Available Abstract Introduction A combination therapy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been used to control proteinuria, following initial demonstration of its efficacy. However, recently concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use. In the following case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of a combination of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension. Case presentation We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy. Conclusion We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination.

  14. Beta blockers may induce in C57BL/6 mice a polyclonal activation of lymphocytes which is not mediated by beta adrenergic receptors.

    Science.gov (United States)

    In, S; Dueymes, M; Fournié, G J

    1988-01-01

    The in vivo immune effects of nine beta (beta)-blockers are studied in C5B1/6 mice after 7 days of treatment. Humoral and cellular studies indicate that several beta-blocking agents, particularly pindolol and acebutolol, may induce a polyclonal activation of lymphocytes. It may involve all the classes and subclasses of immunoglobulins with a preferential effect on IgA and IgG2a. Further investigations, conducted using the laevorotatory and dextrorotatory forms of pindolol indicate that this immune effect is not mediated by specific beta-adrenergic receptors.

  15. Intracoronary abciximab in diabetic patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Piccolo, Raffaele; Eitel, Ingo; Galasso, Gennaro

    2015-01-01

    BACKGROUND: Although intracoronary abciximab failed to improve prognosis compared with intravenous route in unselected ST-segment elevation myocardial infarction (STEMI) patients, little is known about the role of intracoronary abciximab in diabetic patients. OBJECTIVES: To evaluate the efficacy...... of intracoronary abciximab administration in diabetic patients with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: Reperfusional and clinical outcomes of intracoronary abciximab compared with intravenous bolus abciximab according to diabetic status were evaluated in a pooled analysis...... of five randomized trials including 3158 STEMI patients. The primary clinical endpoint of the study was the composite of death or reinfarction at 30-day follow-up. RESULTS: Among 584 diabetic patients (18.5%), the composite of death or reinfarction was significantly reduced with intracoronary abciximab...

  16. The efficacy of mirabegron additional therapy for lower urinary tract symptoms after treatment with α1-adrenergic receptor blocker monotherapy: prospective analysis of elderly men.

    Science.gov (United States)

    Matsuo, Tomohiro; Miyata, Yasuyoshi; Kakoki, Katsura; Yuzuriha, Miki; Asai, Akihiro; Ohba, Kojiro; Sakai, Hideki

    2016-07-29

    Mirabegron is a β3-adrenoreceptor agonist developed for treatment of overactive bladder (OAB). α1-Adrenergic receptor blockers are effective for lower urinary tract symptoms (LUTS) in male patients. However, the efficacy of mirabegron additional treatment in elderly male patients with persistent male LUTS, especially in OAB after monotherapy with α1-adrenergic blockers, is not fully understood. This study was conducted in male LUTS patients who were ≥ 65 years of age and had persistent OAB symptoms, regardless of whether they took an α1-adrenergic receptor blocker orally. Before and 12 weeks after mirabegron additional therapy (50 mg once daily), we evaluated the efficacy of this treatment using the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score (IPSS), and changes in the maximum flow rate (Qmax) and post-void residual urine volume (PVR). We evaluated patients overall and divided into two groups by age: young-old (from 65 to 74 years old) and old-old (from 75 to 84 years old). Fifty men were enrolled in this study. Mirabegron additional therapy improved the total OABSS, total IPSS, and IPSS-quality of life (QOL) score. The voided volume (VV) and Qmax improved after treatment in patients overall. However, there was no significant change in PVR. The total OABSS, total IPSS, and IPSS-QOL score significantly improved in both of the young-old and old-old groups. However, a significant increasing of VV was detected in the young-old group. There were no significant differences in the Qmax or PVR in either group. Mirabegron additional therapy was effective for male patients whose persistent LUTS and particularly OAB was not controlled with α1-adrenergic receptor blocker monotherapy, and mirabegron did not have negative effects on voiding function. Additionally, mirabegron additional therapy was considered effective regardless of patient age. Trial registration number (TRN) trial registration number (TRN) and date of

  17. Determination of several N-methyl-D-aspartate receptor blockers in plasma and brain by a selective high-performance liquid chromatographic method with column switching.

    Science.gov (United States)

    Wyss, R; Bucheli, F; Philipp, W

    1998-02-27

    A general procedure is presented for the determination of several N-methyl-D-aspartate (NMDA) receptor open-channel and subtype-selective blockers, which have been evaluated and developed as neuroprotective drugs for the treatment of brain stroke and trauma. The method involves deproteination of plasma with ethanol, or homogenization of brain samples in ethanol, dilution of the supernatant with ammonium acetate and direct injection into an HPLC column-switching system. Although the investigated NMDA receptor blockers are all tertiary amines, they have quite different structures. However, they are all concentrated on the first column (Purospher RP-18, 125 x 4 mm), whereas polar interfering compounds are washed out with 1% ammonium acetate-acetic acid-acetonitrile (100:1:5, v/v/v). Due to the special selectivity of the Purospher RP-18 material, the analytes and the internal standard are then selectively eluted with 25% acetonitrile (without any buffer in the mobile phase) and transferred to the analytical column (Superspher 60 RP-select B, 250 x 4 mm), where they are separated by gradient elution and detected by UV or fluorescence detection. The low degree of interference allowed the development of sensitive methods with quantification limits of 5 ng/ml for animal plasma (0.4 ml used), 0.5 ng/ml for human plasma (1 ml used) and 50 ng/g for brain tissue (200 mg used).

  18. Significance of initial blood pressure and comorbidity for the efficacy of a fixed combination of an angiotensin receptor blocker and hydrochlorothiazide in clinical practice

    Directory of Open Access Journals (Sweden)

    Roland E Schmieder

    2009-11-01

    Full Text Available Roland E Schmieder1, Markus Schwertfeger2, Peter Bramlage31Department of Nephrology and Hypertension, University Hospital of Erlangen; Germany; 2Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 3Institute of Cardiovascular Pharmacology and Epidemiology, Mahlow, GermanyBackground: Two-thirds of all patients with arterial hypertension need drug combinations to achieve blood pressure (BP goals. Fixed combinations have high efficacy and result in high patient compliance. 300 mg irbesartan plus 25 mg hydrochlorothiazide (HCTZ has been investigated only in clinical trials but not in daily practice.Methods: A multicenter, noninterventional, noncontrolled observational study with 8123 patients seen by 1604 physicians in daily practice. BP reduction (office measurements, co-morbid disease and tolerability were documented over a 6-month observational period.Results: At mean baseline BP of 161 ± 15/94 ± 10 mmHg, administering of fixed combination resulted in a substantial BP reduction averaging 28 ± 15/14 ± 10 mmHg (P < 0.001. Decrease of systolic BP ran parallel with increasing systolic baseline BP (Spearman’s Rho –0.731; P < 0.0001; diastolic BP vs diastolic baseline BP Rho 0.740; P < 0.0001, independent from patient characteristics (age, obesity, diabetes or nephropathy but enhanced with short history of hypertension (P < 0.0001 vs long history, prior beta blockers (P = 0.001 vs prior angiotensin receptor blockers [ARBs], prior calcium channel blockers (P = 0.046 vs prior ARBs and no prior medication (P = 0.012 vs prior ARBs. High compliance (>98% and low incidence of adverse events (0.66% were documented.Conclusions: The fixed combination of 300 mg irbesartan with 25 mg HCTZ was efficacious and tolerable in an unselected patient population in primary care.Keywords: hypertension, combination therapy, obesity, irbesartan, noninterventional study, diuretics

  19. Effects of a pure alpha/beta-adrenergic receptor blocker on monocrotaline-induced pulmonary arterial hypertension with right ventricular hypertrophy in rats.

    Science.gov (United States)

    Ishikawa, Masaya; Sato, Naoki; Asai, Kuniya; Takano, Teruo; Mizuno, Kyoichi

    2009-12-01

    It is unclear how much the sympathetic nervous system is involved in the development of pulmonary arterial hypertension (PAH). The present study examined whether or not a pure alpha/beta-adrenergic receptor blocker (arotinolol) could prevent the development of PAH and right ventricular hypertrophy (RVH) in a rat model of monocrotaline (MCT)-induced PAH. The heart rate, arterial blood pressure (BP), left ventricular pressure, pulmonary artery pressure (PAP), and right ventricular pressure (RVP) were measured after administration of arotinolol or saline for 2 weeks. Ventricular weight and myocyte size were also measured. Mean PAP was increased less in the arotinolol group (n=6), (53 +/-9 vs 21 +/-2 mmHg in the control (n=6); Parotinolol group (41 +/-3 vs 91 +/-14 mmHg in the control, Parotinolol group. The pure alpha/beta-blocker arotinolol prevented the progression of MCT-induced PAH and RVH in rats, suggesting that sympathetic nervous activation might play a role in the development of PAH.

  20. Disparate effects of single endothelin A and B receptor blocker therapy on the progression of renal injury in advanced renovascular disease

    Science.gov (United States)

    Chade, Alejandro R.; Stewart, Nicholas J.; Peavy, Patrick R.

    2013-01-01

    We hypothesized that chronic specific endothelin (ET)-A receptor blockade therapy would reverse renal dysfunction and injury in advanced experimental renovascular disease. To test this, unilateral renovascular disease was induced in 19 pigs and after 6 weeks, single-kidney hemodynamics and function was quantified in vivo using computed-tomography. All pigs with renovascular disease were divided such that 7 were untreated, 7 were treated with ET-A blockers, and 5 were treated with ET-B blockers. Four weeks later, all pigs were re-studied in vivo, then euthanized and ex vivo studies performed on the stenotic kidney to quantify microvascular density, remodeling, renal oxidative stress, inflammation, and fibrosis. RBF, GFR, and redox status were significantly improved in the stenotic kidney after ET-A but not ET-B blockade. Furthermore, only ET-A blockade therapy reversed renal microvascular rarefaction and diminished remodeling, which was accompanied by a marked decreased in renal inflammatory and fibrogenic activity. Thus, ET-A but not ET-B blockade ameliorated renal injury in pigs with advanced renovascular disease by stimulating microvascular proliferation and decreasing the progression of microvascular remodeling, renal inflammation and fibrosis in the stenotic kidney. These effects were functionally consequential since ET-A blockade improved single kidney microvascular endothelial function, RBF, and GFR, and decreased albuminuria. PMID:24352153

  1. 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.

  2. Pharmacologic differences between beta blockers.

    Science.gov (United States)

    Wood, A J

    1984-10-01

    All of the beta blockers act by antagonizing the actions of the endogenous adrenergic agonists epinephrine and norepinephrine at the beta-adrenergic receptors. However, a number of pharmacologic differences exist between the various agents. Some drugs, such as atenolol and metoprolol, are relatively selective for the beta-1-adrenergic receptors, requiring higher concentrations to block beta-2-adrenergic receptors than are required to block beta-1 receptors. It should be noted, however, that these selective beta blockers all block beta-2 receptors when their concentrations are high enough. When patients with asthma must receive a beta blocker, low doses of a selective drug should be used. Recent studies, however, have suggested that the use of a nonselective beta blocker may be desirable to antagonize some beta-2-mediated metabolic effects, such as hypokalemia, induced by epinephrine. Pindolol is the only beta-receptor antagonist available in the United States with intrinsic sympathomimetic, or partial agonist, activity. Such drugs, because of their partial agonist activity, cause some sympathetic stimulation under conditions of low endogenous sympathetic tone, such as while subjects are at rest in the supine position. Under conditions of higher sympathetic tone, pindolol blocks the effects of the endogenous agonists, producing the characteristic effects of a beta blocker. Membrane-stabilizing activity was first recognized with propranolol, and the value of this property has been a source of controversy ever since, but recent studies suggest that propranolol may induce electrophysiologic effects by mechanisms other than beta blockade. Pharmacokinetic differences between the drugs are also of importance.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. The angiotensin receptor blocker and PPAR-γ agonist, telmisartan, delays inactivation of voltage-gated sodium channel in rat heart: novel mechanism of drug action.

    Science.gov (United States)

    Kim, Hyoung Kyu; Youm, Jae Boum; Lee, Sung Ryul; Lim, Se Eun; Lee, Sun-Young; Ko, Tae Hee; Long, Le Thanh; Nilius, Bernd; Won, Du Nam; Noh, Jung-Hyun; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Nari; Han, Jin

    2012-12-01

    Telmisartan is an angiotensin II receptor blocker and partial peroxisome proliferator-activated receptor gamma agonist that modulates the renin-angiotensin-aldosterone system. It is used primarily to manage hypertension, diabetic nephropathy, and congestive heart failure. Recent studies have reported that myocardial infarction (MI) has occurred in telmisartan-treated patients. The purpose of the study was to investigate the specific conditions and underlying mechanisms that may result in telmisartan-induced MI. We evaluated the effect of telmisartan on whole hearts, cardiomyocytes, and cardiac sarcolemmal ion channels. Hearts of 8-week-old male Sprague-Dawley rats were perfused with 3, 10, 30, or 100 μM telmisartan or losartan or with normal Tyrode's solution (control) for 3 h. We found that telmisartan induced myocardial infarction, with an infarct size of 21 % of the total at 30 μM (P action potential duration, and subsequent Ca(2+) overload. Above 30 μM, telmisartan may potentially cause cardiac cell death and MI.

  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

    Science.gov (United States)

    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. The beta-receptor blocker metoprolol alters detoxification processes in the non-target organism Dreissena polymorpha

    Energy Technology Data Exchange (ETDEWEB)

    Contardo-Jara, Valeska, E-mail: contardo@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Pflugmacher, Stephan, E-mail: pflugmacher@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Nuetzmann, Gunnar, E-mail: nuetzmann@igb-berlin.d [Dpt. Ecohydrology, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Kloas, Werner, E-mail: werner.kloas@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Wiegand, Claudia, E-mail: wiegand@biology.sdu.d [University of Southern Denmark Institute of Biology, Campusvej 55, 5230 Odense M (Denmark)

    2010-06-15

    Due to increasing amounts of pharmaceutically active compounds (PhACs) in the aquatic environment, their largely unknown effects to non-target organisms need to be assessed. This study examined physiological changes in the freshwater mussel Dreissena polymorpha exposed to increasing concentrations (0.534, 5.34, 53.4 and 534 mug L{sup -1}) of the beta-blocker metoprolol in a flow-through system for seven days. The two lower concentrations represent the environmentally relevant range. Surprisingly, metallothionein mRNA was immediately up-regulated in all treatments. For the two higher concentrations mRNA up-regulation in gills was found for P-glycoprotein after one day, and after four days for pi class glutathione S-transferase, demonstrating elimination and biotransformation processes, respectively. Additionally, catalase and superoxide dismutase were up-regulated in the digestive gland indicating oxidative stress. In all treated mussels a significant up-regulation of heat shock protein mRNA was observed in gills after four days, which suggests protein damage and the requirement for repair processes. Metoprolol was 20-fold bioaccumulated for environmentally relevant concentrations. - Evidence for significant physiological changes in an aquatic mollusc due to exposure to a pharmaceutically active compound detected by real-time PCR.

  6. Candesartan, an angiotensin II AT₁-receptor blocker and PPAR-γ agonist, reduces lesion volume and improves motor and memory function after traumatic brain injury in mice.

    Science.gov (United States)

    Villapol, Sonia; Yaszemski, Alexandra K; Logan, Trevor T; Sánchez-Lemus, Enrique; Saavedra, Juan M; Symes, Aviva J

    2012-12-01

    Traumatic brain injury (TBI) results in complex pathological reactions, the initial lesion worsened by secondary inflammation and edema. Angiotensin II (Ang II) is produced in the brain and Ang II receptor type 1 (AT₁R) overstimulation produces vasoconstriction and inflammation. Ang II receptor blockers (ARBs) are neuroprotective in models of stroke but little is known of their effect when administered in TBI models. We therefore performed controlled cortical impact (CCI) injury on mice to investigate whether the ARB candesartan would mitigate any effects of TBI. We administered candesartan or vehicle to mice 5 h before CCI injury. Candesartan treatment reduced the lesion volume after CCI injury by approximately 50%, decreased the number of dying neurons, lessened the number of activated microglial cells, protected cerebral blood flow (CBF), and reduced the expression of the cytokine TGFβ1 while increasing expression of TGFβ3. Candesartan-treated mice also showed better motor skills on the rotarod 3 days after injury, and improved performance in the Morris water maze 4 weeks after injury. These results indicate that candesartan is neuroprotective, reducing neuronal injury, decreasing lesion volume and microglial activation, protecting CBF and improving functional behavior in a mouse model of TBI. Co-treatment with a peroxisome proliferator-activated receptor-gamma (PPARγ) antagonist significantly reduced some of the beneficial effects of candesartan after CCI, suggesting that PPARγ activation may contribute to part or to all of the neuroprotective effect of candesartan. Overall, our data suggest that ARBs with dual AT₁R-blocking and PPARγ activation properties may have therapeutic value in treating TBI.

  7. Candesartan, an Angiotensin II AT1-Receptor Blocker and PPAR-γ Agonist, Reduces Lesion Volume and Improves Motor and Memory Function After Traumatic Brain Injury in Mice

    Science.gov (United States)

    Villapol, Sonia; Yaszemski, Alexandra K; Logan, Trevor T; Sánchez-Lemus, Enrique; Saavedra, Juan M; Symes, Aviva J

    2012-01-01

    Traumatic brain injury (TBI) results in complex pathological reactions, the initial lesion worsened by secondary inflammation and edema. Angiotensin II (Ang II) is produced in the brain and Ang II receptor type 1 (AT1R) overstimulation produces vasoconstriction and inflammation. Ang II receptor blockers (ARBs) are neuroprotective in models of stroke but little is known of their effect when administered in TBI models. We therefore performed controlled cortical impact (CCI) injury on mice to investigate whether the ARB candesartan would mitigate any effects of TBI. We administered candesartan or vehicle to mice 5 h before CCI injury. Candesartan treatment reduced the lesion volume after CCI injury by approximately 50%, decreased the number of dying neurons, lessened the number of activated microglial cells, protected cerebral blood flow (CBF), and reduced the expression of the cytokine TGFβ1 while increasing expression of TGFβ3. Candesartan-treated mice also showed better motor skills on the rotarod 3 days after injury, and improved performance in the Morris water maze 4 weeks after injury. These results indicate that candesartan is neuroprotective, reducing neuronal injury, decreasing lesion volume and microglial activation, protecting CBF and improving functional behavior in a mouse model of TBI. Co-treatment with a peroxisome proliferator-activated receptor-gamma (PPARγ) antagonist significantly reduced some of the beneficial effects of candesartan after CCI, suggesting that PPARγ activation may contribute to part or to all of the neuroprotective effect of candesartan. Overall, our data suggest that ARBs with dual AT1R-blocking and PPARγ activation properties may have therapeutic value in treating TBI. PMID:22892395

  8. 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

  9. L-type Calcium Channel Blockers Enhance Trafficking and Function of Epilepsy-associated α1(D219N) Subunits of GABA(A) Receptors.

    Science.gov (United States)

    Han, Dong-Yun; Guan, Bo-Jhih; Wang, Ya-Juan; Hatzoglou, Maria; Mu, Ting-Wei

    2015-09-18

    Gamma-aminobutyric acid type A (GABAA) receptors are the primary inhibitory ion channels in the mammalian central nervous system and play an essential role in regulating inhibition-excitation balance in neural circuits. The α1 subunit harboring the D219N mutation of GABAA receptors was reported to be retained in the endoplasmic reticulum (ER) and traffic inefficiently to the plasma membrane, leading to a loss of function of α1(D219N) subunits and thus idiopathic generalized epilepsy (IGE). We present the use of small molecule proteostasis regulators to enhance the forward trafficking of α1(D219N) subunits to restore their function. We showed that treatment with verapamil (4 μM, 24 h), an L-type calcium channel blocker, substantially increases the α1(D219N) subunit cell surface level in both HEK293 cells and neuronal SH-SY5Y cells and remarkably restores the GABA-induced maximal chloride current in HEK293 cells expressing α1(D219N)β2γ2 receptors to a level that is comparable to wild type receptors. Our drug mechanism study revealed that verapamil treatment promotes the ER to Golgi trafficking of the α1(D219N) subunits post-translationally. To achieve that, verapamil treatment enhances the interaction between the α1(D219N) subunit and β2 subunit and prevents the aggregation of the mutant protein by shifting the protein from the detergent-insoluble fractions to detergent-soluble fractions. By combining (35)S pulse-chase labeling and MG-132 inhibition experiments, we demonstrated that verapamil treatment does not inhibit the ER-associated degradation of the α1(D219N) subunit. In addition, its effect does not involve a dynamin-1 dependent endocytosis. To gain further mechanistic insight, we showed that verapamil increases the interaction between the mutant protein and calnexin and calreticulin, two major lectin chaperones in the ER. Moreover, calnexin binding promotes the forward trafficking of the mutant subunit. Taken together, our data indicate that

  10. 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.

  11. 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.

  12. 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.

  13. Depressor and Anti-Inflammatory Effects of Angiotensin II Receptor Blockers in Metabolic and/or Hypertensive Patients With Coronary Artery Disease: A Randomized, Prospective Study (DIAMOND Study).

    Science.gov (United States)

    Adachi, Sen; Miura, Shin-Ichiro; Shiga, Yuhei; Arimura, Tadaaki; Kuwano, Takashi; Kitajima, Ken; Ike, Amane; Sugihara, Makoto; Iwata, Atsushi; Nishikawa, Hiroaki; Morito, Natsumi; Saku, Keijiro

    2016-10-01

    We compared the efficacy and safety of azilsartan to those of olmesartan in a prospective, randomized clinical trial. Forty-four hypertensive patients who had coronary artery disease (CAD) were enrolled. We randomly assigned patients to changeover from their prior angiotensin II receptor blockers (ARBs) to either azilsartan or olmesartan, and followed the patients for 12 weeks. Office systolic blood pressure (SBP) in the azilsartan group was significantly decreased after 12 weeks. SBP and diastolic blood pressure (DBP) after 12 weeks in the azilsartan group were significantly lower than those in the olmesartan group. The percentage of patients who reached the target BP at 12 weeks (78%) in the azilsartan group was significantly higher than that at 12 weeks (45%) in the olmesartan group. There were no significant changes in pentraxin-3, high-sensitively C-reactive protein or adiponectin in blood after 12 weeks in either group. Although serum levels of creatinine (Cr) in the azilsartan group significantly increased, these changes were within the respective normal range. In conclusion, the ability of azilsartan to reduce BP may be superior to that of prior ARBs with equivalent safety in hypertensive patients with CAD.

  14. Diuretics enhance effects of increased dose of candesartan on ambulatory blood pressure reduction in Japanese patients with uncontrolled hypertension treated with medium-dose angiotensin II receptor blockers.

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    Sakima, Atsushi; Kita, Toshihiro; Nakada, Seigo; Yokota, Naoto; Tamaki, Noboru; Etoh, Takuma; Shimokubo, Toru; Kitamura, Kazuo; Takishita, Shuichi; Ohya, Yusuke

    2014-01-01

    Abstract Although blockade of the renin-angiotensin system by increasing the dose of angiotensin II receptor blockers (ARBs) is recommended to achieve clinical benefits in terms of blood pressure (BP) control and cardiovascular and renal outcomes, the effect of this increased dose on ambulatory BP monitoring has not been evaluated completely in Japanese patients with uncontrolled hypertension undergoing medium-dose ARB therapy. The primary objective of this study was to examine the effect of the relatively high dose of the ARB candesartan (12 mg/day) on 24-h systolic BP and the attainment of target BP levels in uncontrolled hypertension treated with a medium dose of ARBs. A total of 146 hypertensive patients (age: 69.9 ± 9.3 years; females: 65.8%) completed the study. After switching to candesartan at 12 mg/day, all these BP measurements decreased significantly (pdiuretics than those without (p=0.0206). Multivariate analysis revealed a significant correlation between the combined ARB and diuretic therapy, and the change in 24-h systolic BP irrespective of preceding ARBs. In conclusion, the switching therapy to increased dose of candesartan caused significant reductions in office and ambulatory BP levels, and improved the attainment of target BP levels in patients with uncontrolled hypertension treated with a medium dose of ARBs. Combination with diuretics enhanced this effect.

  15. Comparative effectiveness of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers for major renal outcomes in patients with diabetes: A 15-year cohort study.

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    Hon-Yen Wu

    Full Text Available Angiotensin converting enzyme inhibitors (ACEIs and angiotensin II receptor blockers (ARBs are considered to have similar renoprotective effects; so far there has been no consensus about their priorities. This study aimed to compare ACEIs and ARBs for major renal outcomes and survival in a 15-year cohort of adults with diabetes.This study utilized Taiwan's medical and pharmacy claims data in the Longitudinal Cohort of Diabetes Patients. The primary outcome was long-term dialysis, and secondary outcomes were hospitalization for acute kidney injury, hospitalization for hyperkalemia, all-cause death, cardiovascular death, and non-cardiovascular death. Cox proportional hazards models were used to estimate the hazard ratios (HRs and 95% confidence intervals (CIs for outcomes comparing ACEIs with ARBs. We conducted subgroup analyses and interaction tests among patients with different age and comorbid diseases.A total of 34,043 patients received ACEIs and 23,772 patients received ARBs. No differences were found for primary or secondary outcomes in the main analyses. ACEIs showed significantly lower hazard than ARBs for long-term dialysis among patients with cardiovascular disease (HR 0.80, 95% CI 0.66-0.97, interaction P = 0.003 or chronic kidney disease (0.81, 0.71-0.93, interaction P = 0.001.Our analyses show similar effects of ACEIs and ARBs in patients with diabetes. However, ACEIs might provide additional renoprotective effects among patients who have cardiovascular disease or chronic kidney disease.

  16. Use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy to reduce cardiovascular events in high-risk patients: Part 1.

    Science.gov (United States)

    Bommer, William J

    2008-01-01

    Cardiovascular disease is understood as a continuum; risk factors induce a pathophysiologic cascade that culminates in end-organ failure. The renin-angiotensin system (RAS) influences multiple aspects of the pathophysiology via hemodynamic and nonhemodynamic effects. Many long-term clinical trials provide overwhelming evidence of benefits of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) across the cardiovascular continuum, including benefits regarding hypertension, myocardial infarction, stroke, renal disease, and heart failure. Trials also indicate additive or synergistic effects of combination therapy in renal disease and heart failure, a possibility supported by the basic biochemistry of the agents. Discussion of these trials is included in part 1 of this 2-part review. Part 2 of the review will discuss the extensive interaction of the RAS with the cellular and molecular pathophysiology of cardiovascular disease and the cross-continuum effects of ARBs and ACE inhibitors, which raise the possibility that RAS inhibition can offer protection in high-risk patients who do not have symptoms. The benefits of combined ACE inhibitor/ARB therapy in high-risk patients await confirmation; ongoing clinical research in this area will be discussed.

  17. Addition of Aliskiren to Angiotensin Receptor Blocker Improves Ambulatory Blood Pressure Profile and Cardiorenal Function Better than Addition of Benazepril in Chronic Kidney Disease

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    Satoshi Umemura

    2013-07-01

    Full Text Available An altered ambulatory blood pressure (BP and heart rate (HR profile is related to chronic kidney disease (CKD and cardiorenal syndrome. In this study, we examined the effects of aliskiren, when added to angiotensin II type 1 receptor blockers, on ambulatory BP and cardiorenal function in CKD. Thirty-six hypertensive CKD patients were randomly assigned to the aliskiren add-on group (n = 18 or the benazepril add-on group (n = 18. Ambulatory BP and cardiorenal function parameters were measured at baseline and 24 weeks after treatment. Compared with the benazepril group, nighttime systolic BP variability in the aliskiren group was lower after treatment. Albuminuria was decreased in the aliskiren group, but not in the benazepril group. In addition, left ventricular mass index (LVMI was significantly lower in the aliskiren group than in the benazepril group after treatment. In the aliskiren group, multivariate linear regression analysis showed an association between changes in albuminuria and changes in nighttime systolic BP. Furthermore, there were associations between changes in LVMI and changes in daytime HR variability, as well as between changes in LVMI and changes in plasma aldosterone concentration. These results suggest that aliskiren add-on therapy may be beneficial for suppression of renal deterioration and pathological cardiac remodeling through an improvement that is effected in ambulatory BP and HR profiles.

  18. Addition of Aliskiren to Angiotensin Receptor Blocker Improves Ambulatory Blood Pressure Profile and Cardiorenal Function Better than Addition of Benazepril in Chronic Kidney Disease

    Science.gov (United States)

    Ohsawa, Masato; Tamura, Kouichi; Kanaoka, Tomohiko; Wakui, Hiromichi; Maeda, Akinobu; Dejima, Toru; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Toya, Yoshiyuki; Fujikawa, Tetsuya; Umemura, Satoshi

    2013-01-01

    An altered ambulatory blood pressure (BP) and heart rate (HR) profile is related to chronic kidney disease (CKD) and cardiorenal syndrome. In this study, we examined the effects of aliskiren, when added to angiotensin II type 1 receptor blockers, on ambulatory BP and cardiorenal function in CKD. Thirty-six hypertensive CKD patients were randomly assigned to the aliskiren add-on group (n = 18) or the benazepril add-on group (n = 18). Ambulatory BP and cardiorenal function parameters were measured at baseline and 24 weeks after treatment. Compared with the benazepril group, nighttime systolic BP variability in the aliskiren group was lower after treatment. Albuminuria was decreased in the aliskiren group, but not in the benazepril group. In addition, left ventricular mass index (LVMI) was significantly lower in the aliskiren group than in the benazepril group after treatment. In the aliskiren group, multivariate linear regression analysis showed an association between changes in albuminuria and changes in nighttime systolic BP. Furthermore, there were associations between changes in LVMI and changes in daytime HR variability, as well as between changes in LVMI and changes in plasma aldosterone concentration. These results suggest that aliskiren add-on therapy may be beneficial for suppression of renal deterioration and pathological cardiac remodeling through an improvement that is effected in ambulatory BP and HR profiles. PMID:23887656

  19. Development and characterization of colloidal soft nano-carriers for transdermal delivery and bioavailability enhancement of an angiotensin II receptor blocker.

    Science.gov (United States)

    Hathout, Rania M; Elshafeey, Ahmed H

    2012-10-01

    The purpose of this study was to develop and characterize a successful colloidal soft nano-carrier viz. microemulsion system, for the transdermal delivery of an angiotensin II receptor blocker: olmesartan medoxomil. Different microemulsion formulations were prepared. The microemulsions were characterized visually, with the polarizing microscope, and by photon correlation spectroscopy. In addition, the pH and conductivity (σ) of the formulations were measured. The type and structure of microemulsions formed were determined using conductivity measurements analysis, Freezing Differential Scanning Calorimetry (FDSC) and Diffusion-Ordered Spectroscopy (DOSY). Alterations in the molecular conformations of porcine skin were determined using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) biophysical assessment. Olmesartan medoxomil delivery from the investigated formulations was assessed across porcine skin ex-vivo using Franz diffusion cells; the drug was analyzed by liquid chromatography mass spectroscopy (LC/MS/MS). A comparative pharmacokinetic study was done on healthy human subjects between the selected microemulsion and the commercial oral tablets. The physico-chemical and spectroscopic methods revealed the presence of water-in-oil and bicontinuous structures. Biophysical assessment demonstrated various stratum corneum (SC) changes. Olmesartan medoxomil was delivered successfully across the skin with flux achieving 3.65μgcm(-2)h(-1). Higher bioavailability compared to commercial oral tablets with a more sustainment behavior was achieved. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. TRC120038, a Novel Dual AT1/ETA Receptor Blocker for Control of Hypertension, Diabetic Nephropathy, and Cardiomyopathy in ob-ZSF1 Rats

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    Anookh Mohanan

    2011-01-01

    Full Text Available In hypertensive subjects, angiotensin II and endothelin participate in a manner involving closely interwoven pathways in increasing blood pressure (BP and inducing end organ damage. The primary objective of this study was to determine the effect of TRC120038, a novel dual AT1/ETA receptor blocker on BP, in obese Zucker spontaneously hypertensive fatty rats (ob-ZSF1, an animal model of moderate hypertension, diabetes with progressive renal and cardiac dysfunction. Ob-ZSF1 rats loaded with 0.5% salt were treated with TRC120038 (11.8 mg/kg bid. or candesartan cilexetil (0.3 mg/kg od. or vehicle control. Blood pressure (by radio-telemetry and renal functional markers were monitored throughout the study. Cardiac function was assessed terminally by pressure volume catheter. Markers for renal dysfunction were measured and changes were evaluated histopathologically. TRC120038 showed greater fall in both systolic and diastolic BP in comparison to candesartan at its maximum antihypertensive dose. TRC120038 also reduced the severity of renal dysfunction and preserved cardiac function in ob-ZSF1 rat.

  1. Combined treatment with chemokine receptor 5 blocker and cyclosporine induces prolonged graft survival in a mouse model of cardiac transplantation.

    Science.gov (United States)

    Jun, Li; Kailun, Zhang; Aini, Xie; Lei, Xu; Guohua, Wang; Sihua, Wang; Ping, Ye; Tucheng, Sun; Xionggang, Jiang; Wenwei, Chen; Jiahong, Xia

    2010-04-01

    Inhibition of chemokine receptor 5 (CCR5), a chemokine receptor expressed on activated T cells, is efficacious in modulating inflammation and immunity as well as in patients with human immunodeficiency virus infection. This study examined the effect and mechanism of CCR5 blockade in combination with cyclosporine in prolonging cardiac allograft survival in mice. Hearts from BALB/c mice were transplanted into C57BL/10 recipients. They were administrated with anti-CCR5 antibody (Ab) or control Ab and cyclosporine or phosphate-buffered (PBS) saline, respectively. To investigate the role of regulatory cells, naïve mice (secondary recipients) underwent adoptive transfer of splenocytes from anti-CCR5 Ab plus cyclosporine-treated recipients and cardiac allograft transplantation. Compared with recipients treated with control Ab plus PBS, allografts treated with anti-CCR5 Ab and cyclosporine showed significantly prolonged survival (p cyclosporine-treated recipients induced significantly prolonged survival in secondary recipients (p cyclosporine is effective in protecting the cardiac allograft in a robust murine model. This effect is partly mediated by regulatory cell recruitment and control of effector cell infiltration.

  2. Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: (/sup 3/H)chlorpromazine labels homologous residues in the. beta. and delta chains

    Energy Technology Data Exchange (ETDEWEB)

    Giraudat, J.; Dennis, M.; Heidmann, T.; Haumont, P.Y.; Lederer, F.; Changeux, J.P.

    1987-05-05

    The membrane-bound acetylcholine receptor from Torpedo marmorata was photolabeled by the noncompetitive channel blocker (/sup 3/H)chlorpromazine under equilibrium conditions in the presence of the agonist carbamoylcholine. The amount of radioactivity incorporated into all subunits was reduced by addition of phencyclidine, a specific ligand for the high-affinity site for noncompetitive blockers. The labeled ..beta.. chain was purified and digested with trypsin or CNBr, and the resulting fragments were fractionated by high-performance liquid chromatography. Sequence analysis resulted in the identification of Ser-254 and Leu-257 as residues labeled by (/sup 3/H)chlorpromazine in a phencyclidine-sensitive manner. These residues are located in the hydrophobic and potentially transmembrane segment M II of the ..beta.. chain, a region homologous to that containing the chlorpromazine-labeled Ser-262 in the delta chain. These results show that homologous regions of different receptor subunits contribute to the unique high-affinity site for noncompetitive blockers, a finding consistent with the location of this site on the axis of symmetry of the receptor molecule.

  3. GRIN2D Recurrent De Novo Dominant Mutation Causes a Severe Epileptic Encephalopathy Treatable with NMDA Receptor Channel Blockers.

    Science.gov (United States)

    Li, Dong; Yuan, Hongjie; Ortiz-Gonzalez, Xilma R; Marsh, Eric D; Tian, Lifeng; McCormick, Elizabeth M; Kosobucki, Gabrielle J; Chen, Wenjuan; Schulien, Anthony J; Chiavacci, Rosetta; Tankovic, Anel; Naase, Claudia; Brueckner, Frieder; von Stülpnagel-Steinbeis, Celina; Hu, Chun; Kusumoto, Hirofumi; Hedrich, Ulrike B S; Elsen, Gina; Hörtnagel, Konstanze; Aizenman, Elias; Lemke, Johannes R; Hakonarson, Hakon; Traynelis, Stephen F; Falk, Marni J

    2016-10-06

    N-methyl-D-aspartate receptors (NMDARs) are ligand-gated cation channels that mediate excitatory synaptic transmission. Genetic mutations in multiple NMDAR subunits cause various childhood epilepsy syndromes. Here, we report a de novo recurrent heterozygous missense mutation-c.1999G>A (p.Val667Ile)-in a NMDAR gene previously unrecognized to harbor disease-causing mutations, GRIN2D, identified by exome and candidate panel sequencing in two unrelated children with epileptic encephalopathy. The resulting GluN2D p.Val667Ile exchange occurs in the M3 transmembrane domain involved in channel gating. This gain-of-function mutation increases glutamate and glycine potency by 2-fold, increases channel open probability by 6-fold, and reduces receptor sensitivity to endogenous negative modulators such as extracellular protons. Moreover, this mutation prolongs the deactivation time course after glutamate removal, which controls the synaptic time course. Transfection of cultured neurons with human GRIN2D cDNA harboring c.1999G>A leads to dendritic swelling and neuronal cell death, suggestive of excitotoxicity mediated by NMDAR over-activation. Because both individuals' seizures had proven refractory to conventional antiepileptic medications, the sensitivity of mutant NMDARs to FDA-approved NMDAR antagonists was evaluated. Based on these results, oral memantine was administered to both children, with resulting mild to moderate improvement in seizure burden and development. The older proband subsequently developed refractory status epilepticus, with dramatic electroclinical improvement upon treatment with ketamine and magnesium. Overall, these results suggest that NMDAR antagonists can be useful as adjuvant epilepsy therapy in individuals with GRIN2D gain-of-function mutations. This work further demonstrates the value of functionally evaluating a mutation, enabling mechanistic understanding and therapeutic modeling to realize precision medicine for epilepsy. Copyright © 2016

  4. Effects of abciximab on key pattern of human coronary restenosis in vitro: impact of the SI/MPL-ratio

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    Baur Regine

    2006-04-01

    Full Text Available Abstract Background The significant reduction of angiographic restenosis rates in the ISAR-SWEET study (intracoronary stenting and antithrombotic regimen: is abciximab a superior way to eliminate elevated thrombotic risk in diabetes raises the question of whether abciximab acts on clopidogrel-independent mechanisms in suppressing neointimal hyperplasia. The current study investigates the direct effect of abciximab on ICAM-1 expression, migration and proliferation. Methods ICAM-1: Part I of the study investigates in cytoflow studies the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1. Migration: Part II of the study explored the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml on migration of HCMSMC over a period of 24 h. Proliferation: Part III of the study investigated the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml on proliferation of HUVEC, HCAEC, and HCMSMC after an incubation period of 5 days. Results ICAM-1: In human venous endothelial cells (HUVEC, human coronary endothelial cells (HCAEC and human coronary medial smooth muscle cells (HCMSMC no inhibitory or stimulatory effect on expression of ICAM-1 was detected. Migration: After incubation of HCMSMC with abciximab in concentrations of 0.0002 – 2 μg/ml a stimulatory effect on cell migration was detected, statistical significance was achieved after incubation with 0.002 μg/ml (p 1. Conclusion Thus, the anti-restenotic effects of systemically administered abciximab reported in the ISAR-SWEET-study were not caused by a direct inhibitory effect on ICAM-1 expression, migration or proliferation.

  5. Calcium channel blocker overdose

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium-channel blockers are a type of medicine used to ...

  6. Beta blockers: A new role in chemotherapy

    Science.gov (United States)

    Nagaraja, Archana S; Sadaoui, Nouara C.; Lutgendorf, Susan K.; Ramondetta, Lois M.; Sood, Anil K.

    2014-01-01

    Beta-blockers are a class of drugs widely used to treat cardiac, respiratory and other ailments. They act by blocking beta-adrenergic receptor–mediated signalling. Studies in various cancers have shown that patients taking a beta-blocker have higher survival and lower recurrence and metastasis rates. This is supported by several preclinical and in vitro studies showing that adrenergic activation modulates apoptosis, promotes angiogenesis and other cancer hallmarks, and these effects can be abrogated by beta-blockers. These studies provide a rationale for the use of beta-blockers as adjuvants with cancer chemotherapy. However, all published studies so far are retrospective, and most do not take into account the specific beta-blocker used or address which is most likely to benefit cancer patients. The published epidemiological studies are correlative and have not examined the adrenergic receptor status of the tumours. Knowledge of the beta-adrenergic receptor status of tumour cells is essential in choosing the best beta-blocker for adjuvant therapy. A comprehensive, prospective study is necessary to prove definitively the utility of using beta-blockers with chemotherapy and to identify the specific betablocker most likely to benefit patients with cancer. PMID:23919278

  7. The effect of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use on mortality in patients with chronic kidney disease: a meta-analysis of observational studies.

    Science.gov (United States)

    Qin, Yuchen; Chen, Tao; Chen, Qi; Lv, Jia Yi; Qi, Na; Wu, Cheng; He, Jia

    2016-05-01

    There has been much controversy over the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) on patients with renal dysfunction. The purpose of this study was to summarize the evidence regarding the effect of ACEIs/ARBs administration on mortality in patients with nondialysis-dependent chronic kidney disease (CKD) by using a meta-analytic approach. We searched the PubMed, Embase, and Web of Science databases for studies on the effect of ACEIs/ARBs administration on mortality in patients with nondialysis-dependent CKD published before March 2015. Summary effect estimates with 95% confidence intervals were derived using the random-effects model, no matter whether the heterogeneity between the included studies was of statistical significance or not. Subgroup analyses, sensitivity analyses, and publication bias tests were performed. Up to 25 March 2015, 10 cohort studies were included in this meta-analysis. The hazard risk of the association between ACEIs/ARBs administration and overall mortality was 0.83 (95% confidence interval 0.78-0.87) using a random-effects model with no heterogeneity (heterogeneity test I(2)  = 43.8%, p = 0.067) and publication bias (Egger's test, p = 0.763). The subgroup was divided according to estimated glomerular filtration rate, duration of follow-up, Newcastle-Ottawa Scale star, and proportion of patients with common complications including heart failure, diabetes mellitus, and hypertension. Improved survival outcomes were observed in all subgroups analysis. Sensitivity analysis proved that overall estimated effect was robust. This meta-analysis suggested that the use of ACEIs/ARBs in patients with nondialysis-dependent CKD was associated with improved survival. However, randomized studies are needed to confirm these findings and further establish causal relationship. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Alterations in expression of Cat-315 epitope of perineuronal nets during normal ageing, and its modulation by an open-channel NMDA receptor blocker, memantine.

    Science.gov (United States)

    Yamada, Jun; Ohgomori, Tomohiro; Jinno, Shozo

    2017-06-15

    The perineuronal net (PNN), a specialized aggregate of the extracellular matrix, is involved in neuroprotection against oxidative stress, which is now recognized as a major contributor to age-related decline in brain functions. In this study, we investigated the age-related molecular changes of PNNs using monoclonal antibody Cat-315, which recognizes human natural killer-1 (HNK-1) glycan on aggrecan-based PNNs. Western blot analysis showed that the expression levels of Cat-315 epitope in the hippocampus were higher in middle-aged (MA, 12-month-old) mice than in young adult (YA, 2-month-old) mice. Although there were no differences in the expression levels of Cat-315 epitope between old age (OA, 20-month-old) and MA mice, Cat-315 immunoreactivity was also detected in astrocytes of OA mice. To focus on Cat-315 epitope in PNNs, we used YA and MA mice in the following experiments. Optical disector analysis showed that there were no differences in the numbers of Cat-315-positive (Cat-315(+) ) PNNs between YA and MA mice. Fluorescence intensity analysis indicated that Cat-315 immunoreactivity in PNNs increased with age in the dorsal hippocampus, which is mainly involved in cognitive functions. Administration of an open-channel blocker of NMDA receptor, memantine, reduced the expression levels of Cat-315 epitope in the hippocampus. Furthermore, the numbers of glutamatergic and GABAergic terminals colocalized with Cat-315 epitope around parvalbumin-positive neurons were decreased by memantine. These findings provide novel insight into the involvement of PNNs in normal brain ageing, and suggest that memantine may counteract the age-related alterations in expression levels of Cat-315 epitope via regulation of its subcellular localization. © 2017 Wiley Periodicals, Inc.

  9. 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.

  10. Effect of preoperative angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker use on hemodynamic variables in pediatric patients undergoing cardiopulmonary bypass.

    Science.gov (United States)

    Ajuba-Iwuji, Chinwe C; Puttreddy, Sahitya; Maxwell, Bryan G; Bembea, Melania; Vricella, Luca; Heitmiller, Eugenie

    2014-10-01

    Some have suggested that children undergoing cardiac surgery who receive angiotensin-converting enzyme (ACE) inhibitors experience a greater degree of hypotension after anesthesia induction and in the immediate postcardiopulmonary bypass period than children who did not receive these drugs. Therefore, we examined the effect of ACE inhibitor/angiotensin II receptor blocker (ARB) therapy on intraoperative hemodynamics and vasopressor use in pediatric patients undergoing cardiac surgery. In a retrospective cohort study of patients younger than 18 years who underwent cardiopulmonary bypass between March 1, 2010, and April 1, 2011, we compared intraoperative hemodynamics and vasopressor use between patients who received preoperative ACE inhibitor/ARB therapy and those who did not. The primary outcome was vasoactive infusion score after cardiopulmonary bypass. The occurrence of hypotension did not differ significantly between the ACE inhibitor/ARB group and the control group during induction of anesthesia or at any time point after cardiopulmonary bypass. At 0, 30, 60, and 90 minutes after cessation of cardiopulmonary bypass, patients on ACE inhibitor/ARB therapy tended to have a higher vasoactive infusion score (7.1, 7.6, 9.4, and 11.3) than patients in the control group (6.3, 6.1, 6.0, and 6.7). Although this difference became more pronounced over time, it did not reach statistical significance. The use of preoperative ACE inhibitors and ARBs in pediatric patients undergoing cardiac surgery did not significantly increase the incidence of hypotension after induction of anesthesia and did not increase significantly the vasoconstrictor requirements upon weaning from cardiopulmonary bypass; however, additional prospective studies are needed. © The Author(s) 2014.

  11. Angiotensin II receptor blockers suppress the release of stromal cell-derived factor-1α from infarcted myocardium in patients with acute myocardial infarction.

    Science.gov (United States)

    Yoshizaki, Toru; Uematsu, Manabu; Obata, Jun-Ei; Nakamura, Takamitsu; Fujioka, Daisuke; Watanabe, Kazuhiro; Nakamura, Kazuto; Kugiyama, Kiyotaka

    2018-04-01

    Although angiotensin II receptor blockers (ARBs) have been shown to have anti-inflammatory effects on infarcted myocardium in experimental models, little is known in humans. Stromal cell-derived factor-1α (SDF-1α), a pro-inflammatory chemokine, is released from infarcted tissue in patients with acute myocardial infarction (AMI). This study examined whether ARBs suppress SDF-1α production in the infarcted lesion in patients with AMI. SDF-1α levels were measured by enzyme-linked immunosorbent assays in plasma obtained from the aortic root (AO) and the anterior interventricular vein (AIV) in 50 patients with an anterior AMI. Measurement of SDF-1α levels and left ventriculography were repeated at discharge and 6 months after AMI. Patients were divided into 2 groups according to treatment with ARBs, which were administered at the discretion of the attending physician after admission. The AIV-AO gradient of SDF-1α, reflecting SDF-1α release from the infarcted myocardial region, decreased between the time of discharge and 6 months after AMI in patients taking an ARB. In contrast, the SDF-1α transcardiac gradient did not change in patients not taking an ARB. Among the clinical parameters tested, only the use of ARBs was significantly associated with percent changes in the SDF-1α transcardiac gradient from the time of discharge to 6 months after AMI in a linear regression analysis (r=-0.31, p=0.03). The SDF-1α transcardiac gradient 6 months after AMI was inversely correlated with the percent change in left ventricular (LV) ejection fraction (r=-0.52, pinfarcted myocardial region, which was associated with improvement in LV dysfunction and adverse remodeling in AMI survivors. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  12. Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

    Science.gov (United States)

    Fröhlich, Hanna; Nelges, Christoph; Täger, Tobias; Schwenger, Vedat; Cebola, Rita; Schnorbach, Johannes; Goode, Kevin M; Kazmi, Syed; Katus, Hugo A; Cleland, John G F; Clark, Andrew L; Frankenstein, Lutz

    2016-08-01

    Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Takanori [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011 (Japan); Yamagishi, Sho-ichi, E-mail: shoichi@med.kurume-u.ac.jp [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011 (Japan); Takeuchi, Masayoshi [Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa (Japan); Ueda, Seiji; Fukami, Kei; Okuda, Seiya [Department of Medicine, Kurume University School of Medicine, Kurume (Japan)

    2009-07-24

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}). Although nifedipine did not affect expression levels of PPAR-{gamma}, it increased the PPAR-{gamma} transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-{gamma} activation.

  14. Catheter-Directed Intra-Arterial Abciximab Administration for Acute Thrombotic Occlusions during Neurointerventional Procedures

    OpenAIRE

    Duncan, I.C.; Fourie, P.A.

    2002-01-01

    Abciximab is one of a new class of platelet aggregation inhibitors that has to date been used mainly in the management of acute coronary ischaemic syndromes or during cardiac intervention for the prevention and treatment of acute vessel occlusion during and after angioplasty or stent placement. More recently, it has begun to play a similar role in neurointerventional work. Its administration during acute stent or vessel occlusions has usually been via systemic intravenous infusion. We describ...

  15. Variability of platelet aggregate dispersal with glycoprotein IIb-IIIa antagonists eptifibatide and abciximab.

    Science.gov (United States)

    Speich, H E; Earhart, A D; Hill, S N; Cholera, S; Kueter, T J; Smith, J N; White, M M; Jennings, L K

    2009-06-01

    Utilization of glycoprotein IIb-IIIa (GPIIb-IIIa) inhibitors improves outcomes of patients with acute coronary syndromes (ACS), including those undergoing percutaneous coronary intervention (PCI). These results may be related to the ability of the inhibitors to destabilize coronary thrombi, reduce microembolization, and restore vessel patency. To evaluate in vitro the ability of GPIIb-IIIa antagonists, abciximab and eptifibatide, to promote the disaggregation of platelet-rich thrombus. Antagonist-induced disaggregation was assayed in plasma by aggregometry, as well as in whole blood by point of care and capillary perfusion systems. Fibrinogen dissociation from the platelet surface was quantified by flow cytometry. Significant disaggregation of 5 microm ADP-induced aggregates was observed after addition of either agent. The maximum extent and rate of disaggregation were significantly higher with eptifibatide than with abciximab. Both antagonists also dispersed 2 microg mL(-1) collagen-induced aggregates, again with eptifibatide having a greater effect. Eptifibatide, but not abciximab (up to 10 microg mL(-1)), was efficient at dissociating aggregates to single platelets in whole blood and dispersing aggregates that had been aged for 30 min before treatment. Eptifibatide also reduced existing thrombus burden in the perfusion model under arterial flow conditions. A key mechanism of aggregate dispersal was antagonist-induced displacement of platelet-bound fibrinogen, which was greater with eptifibatide, a competitive inhibitor of fibrinogen binding, than with the noncompetitive inhibitor, abciximab. These results suggest that drug concentration and residence time, along with thrombus extent and age, may be critical determinants in promoting timely recanalization.

  16. Controlled reperfusion with intravenous bivalirudin and intracoronary abciximab combination therapy in the porcine myocardial infarction model.

    Science.gov (United States)

    Buszman, Piotr P; Wojakowski, Wojciech; Milewski, Krzysztof; Dębiński, Marcin; Pająk, Jacek; Aboodi, Michael S; Jackiewicz, Wanda; Kawka, Magdalena; Bochenek, Andrzej; Prats, Jayne; Granada, Juan F; Kałuża, Greg L; Buszman, Pawel E

    2012-08-01

    The reperfusion injury (RI) remains a significant limitation of primary PCI, therefore we evaluated the role of intracoronary abciximab and bivalirudin for anticoagulation on myocardial salvage and RI in the porcine model of ischemia/reperfusion. Myocardial infarction was induced in 23 pigs by 60-minute over-the-wire (OTW) balloon occlusion of the LAD. Animals received intravenous bivalirudin and then five minutes prior to reperfusion, either a coronary downstream infusion of abciximab (n=11) or saline (n=12) through the central lumen of an OTW catheter. All animals were followed for 48 hours. Histological analysis showed that infarct area (IA) and area at risk (AAR) were comparable between groups (IA/AAR%: 57.6 ± 8% vs. 57.1 ± 7%, p=0.8). Confirming this trend, biochemical markers (troponin I, TNF-alpha, IL-6, hsCRP, adiponectin, and VCAM) and left ventricular ejection fraction were also similar at 48 hours. Adhesion markers like ICAM and P-selectin were significantly decreased in the study group, nevertheless histological evidence of leukocyte extravasation was similar. The enhancement of apoptosis by TUNEL was comparable in both groups. The number of hemorrhagic infarctions confirmed by micro and macroscopic evaluation tended to be higher in the study group (70% vs. 20%, p=0.07). Despite lowered concentrations of adhesion molecules, intracoronary abciximab with peripheral bivalirudin is not superior to bivalirudin unaided in terms of myocardial salvage caused by RI in the porcine ischemia/reperfusion model. This might be due to local hemorrhage caused by abciximab. Copyright © 2011. Published by Elsevier Ltd.

  17. Eptifibatide is noninferior to abciximab in primary percutaneous coronary intervention: results from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry).

    Science.gov (United States)

    Akerblom, Axel; James, Stefan K; Koutouzis, Michail; Lagerqvist, Bo; Stenestrand, Ulf; Svennblad, Bodil; Oldgren, Jonas

    2010-08-03

    The aim of this study was to test the noninferiority of eptifibatide relative to abciximab in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Glycoprotein IIb/IIIa inhibitors are recommended by international guidelines in patients with acute coronary syndromes undergoing PCI. Abciximab is recommended with a higher level of evidence than eptifibatide in patients with STEMI. No large, prospective, randomized trial comparing abciximab and eptifibatide has been published. All (n = 11,479) STEMI patients in Sweden who underwent primary PCI and received either eptifibatide or abciximab from 2004 to 2007 were derived from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). The primary end point was death or myocardial infarction (MI) during 1-year follow-up, with adjustment for baseline differences with a multivariate logistic regression analysis including propensity score. The pre-specified noninferiority margin was set to 1.29. The combined end point occurred in 353 of 2,355 patients (15.0%) treated with eptifibatide and in 1,432 of 9,124 patients (15.7%) treated with abciximab. The unadjusted odds ratio (OR) for eptifibatide versus abciximab was 0.95 (95% confidence interval [CI]: 0.84 to 1.08). Multivariate adjustment (n = 11,317) confirmed noninferiority, with an OR of 0.94 (95% CI: 0.82 to 1.09). The adjusted secondary end points of death and MI separately also showed noninferiority, with ORs of 0.99 (95% CI: 0.82 to 1.19) and 0.88 (95% CI: 0.73 to 1.05), respectively. This large registry study suggests that eptifibatide is noninferior to abciximab in patients with STEMI undergoing primary PCI with respect to death or MI during 1 year, thereby supporting the use of either drug in clinical practice. Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. A Systematic Review of Outcomes Associated With Withholding or Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Before Noncardiac Surgery.

    Science.gov (United States)

    Hollmann, Caryl; Fernandes, Nicole L; Biccard, Bruce M

    2018-01-29

    The global rate of major noncardiac surgical procedures is increasing annually, and of those patients presenting for surgery, increasing numbers are taking either an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin receptor blocker (ARB). The current recommendations of whether to continue or withhold ACE-I and ARB in the perioperative period are conflicting. Previous meta-analyses have linked preoperative ACE-I/ARB therapy to the increased incidence of postinduction hypotension; however, they have failed to correlate this with adverse patient outcomes. The aim of this meta-analysis was to determine whether continuation or withholding ACE-I or ARB therapy in the perioperative period is associated with mortality and major morbidity. This meta-analysis was prospectively registered on PROSPERO (CRD42017055291). A comprehensive search of MEDLINE (PubMed), CINAHL (EBSCO host), ProQuest, Cochrane database, Scopus, and Web of Science was conducted on December 6, 2016. We included adult patients >18 years of age on chronic ACE-I or ARB therapy who underwent noncardiac surgery in which ACE-I or ARB was either withheld or continued on the morning of surgery. Primary outcomes included all-cause mortality and major cardiac events (MACE). Secondary outcomes included the risk of congestive heart failure, acute kidney injury, stroke, intraoperative/postoperative hypotension, and the length of hospital stay. After abstract review, the full text of 25 studies was retrieved, of which 9 fulfilled the inclusion criteria: 5 were randomized control trials, and 4 were cohort studies. These studies included a total of 6022 patients on chronic ACE-I/ARB therapy before noncardiac surgery. A total of 1816 patients withheld treatment the morning of surgery and 4206 continued their ACE-I/ARB. Preoperative demographics were similar between the 2 groups. Withholding ACE-I/ARB therapy was not associated with a difference in mortality (odds ratio [OR], 0.97; 95% confidence interval

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

    Science.gov (United States)

    2012-01-01

    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 price adjustment (−156.9%, p drugs showed long-term trend increases after price adjustments in 2001 (72.2%, p Price adjustments did not achieve long-term cost

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

    Directory of Open Access Journals (Sweden)

    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

  1. Prescriptions for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and monitoring of serum creatinine and potassium in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Pei-Tzu Wang

    2012-09-01

    Full Text Available Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs are commonly used in patients with chronic kidney disease (CKD. We studied the status of ACEI/ARB prescriptions and serum creatinine (Scr and potassium monitoring in CKD patients. A retrospective observational study was conducted on patients who had at least two sets of Scr data at outpatient visit. Estimated glomerular filtration rate (eGFR based on the second Scr value was calculated using the Modification of Diet in Renal Disease four-variable equation. CKD was defined and staged according to the National Kidney Foundation Disease Outcomes Quality Initiative Guideline. Patients with diabetes and/or hypertension with an eGFR over 60 mL/min/1.73 m2 and without proteinuria were defined as the CKD-at-risk group. The percentages and factors associated with ACEI/ARB prescription and Scr and potassium monitoring were calculated and analyzed by logistic regression. Among the 5714 subjects included, ACEIs/ARBs were prescribed to over 50% of patients in the CKD-at-risk group and in CKD stages 1–5. After adjusting for age, sex, potassium level, eGFR, and co-morbidities, the odds ratios for prescriptions of ACEIs/ARBs were 1.66 [95% confidence interval (CI 1.44–1.91, p < 0.001 and 2.80 (95% CI 2.12–3.70, p < 0.001 in CKD stage 3, and stages 4 and 5, respectively, compared with the reference group (eGFR≥60 mL/min/1.73 m2. During the year of ACEI/ARB treatment, Scr was monitored in 91.6% of ACEI/ARB-treated patients, while potassium was monitored in only 38.1%. Renal function status was the independent factor for monitoring of Scr and potassium. In conclusion, prescription of ACEIs/ARBs was common in all stages of CKD. Most patients underwent Scr monitoring, but potassium monitoring was less frequent, and this should be improved in clinical practice.

  2. Benefits from intracoronary as compared to intravenous abciximab administration for STEMI patients undergoing primary angioplasty: a meta-analysis of 8 randomized trials.

    NARCIS (Netherlands)

    Luca, G. De; Verdoia, M.; Suryapranata, H.

    2012-01-01

    BACKGROUND: Adjunctive abciximab administration has been demonstrated to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion.

  3. 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.

    Science.gov (United States)

    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.

  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.......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. The roles of beta-adrenergic receptors in tumorigenesis and the possible use of beta-adrenergic blockers for cancer treatment: possible genetic and cell-signaling mechanisms

    Directory of Open Access Journals (Sweden)

    Luong KV

    2012-12-01

    Full Text Available Khanh vinh quốc Lương, Lan Thi Hoàng NguyễnVietnamese American Medical Research Foundation, Westminster, California, USAAbstract: Cancer is the leading cause of death in the USA, and the incidence of cancer increases dramatically with age. Beta-adrenergic blockers appear to have a beneficial clinical effect in cancer patients. In this paper, we review the evidence of an association between β-adrenergic blockade and cancer. Genetic studies have provided the opportunity to determine which proteins link β-adrenergic blockade to cancer pathology. In particular, this link involves the major histocompatibility complex class II molecules, the renin–angiotensin system, transcription factor nuclear factor-kappa-light-chain-enhancer of activated B cells, poly(ADP-ribose polymerase-1, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate oxidase. Beta-adrenergic blockers also exert anticancer effects through non-genomic factors, including matrix metalloproteinase, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase-2, oxidative stress, and nitric oxide synthase. In conclusion, β-adrenergic blockade may play a beneficial role in cancer treatment. Additional investigations that examine β-adrenergic blockers as cancer therapeutics are required to further elucidate this role.Keywords: β-adrenergic blocker, neoplasm, β-adrenergic antagonism, non-genomic factor

  6. 1-Year Outcomes With Intracoronary Abciximab in Diabetic Patients Undergoing Primary Percutaneous Coronary Intervention

    DEFF Research Database (Denmark)

    Piccolo, Raffaele; Eitel, Ingo; Galasso, Gennaro

    2016-01-01

    .68 to 1.33; p = 0.77), resulting in a significant interaction (p = 0.034). Among diabetic patients, intracoronary versus intravenous abciximab bolus was associated with a significantly reduced risk of death (5.8% vs. 11.2%; HR: 0.51; 95% CI: 0.26 to 0.98; p = 0.043) and definite/probable stent thrombosis......BACKGROUND: Diabetic patients are at increased risk for future cardiovascular events after ST-segment elevation myocardial infarction (STEMI). Administration of an intracoronary abciximab bolus during primary percutaneous coronary intervention (PCI) may be beneficial in this high-risk subgroup....... OBJECTIVES: This study sought to report the 1-year clinical outcomes and cardiac magnetic resonance (CMR) findings in STEMI patients with and without diabetes randomized to intracoronary or intravenous abciximab bolus at the time of primary PCI. METHODS: Patient-level data from 3 randomized trials were...

  7. Efficacy and safety of abciximab in diabetic patients who underwent percutaneous coronary intervention with thienopyridines loading: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yihua Wu

    Full Text Available BACKGROUND: It has been controversial whether abciximab offered additional benefits for diabetic patients who underwent percutaneous coronary intervention (PCI with thienopyridines loading. METHODS: MEDLINE, EMBASE, the Cochrane library clinical trials registry, ISI Science Citation Index, ISI Web of Knowledge and China National Knowledge Infrastructure (CNKI were searched, supplemented with manual-screening for relevant publications. Quantitative meta-analyses were performed to assess differences between abciximab groups and controls with respect to post-PCI risk of major cardiac events (MACEs, angiographic restenosis and bleeding complications. RESULTS: 9 trials were identified, involving 2,607 diabetic patients receiving PCI for coronary artery diseases. Among those patients who underwent elective PCI or primary PCI, pooling results showed that abciximab did not significantly reduce risks of MACEs (for elective-PCI patients: RR(1-month: 0.93, 95% CI: 0.60-1.44; RR(1-year: 0.95, 95% CI: 0.81-1.11; for primary-PCI patients: RR(1-month: 1.05, 95% CI: 0.70-1.57; RR(1-year: 0.98, 95% CI: 0.80-1.21, nor all-cause mortality, re-infarction and angiographic restenosis in either group. The only beneficial effect by abciximab appeared to be a decrease 1-year TLR (target lesion revascularization risk in elective-PCI patients (RR1-year: 0.83, 95% CI: 0.70-0.99. Moreover, occurrence of minor bleeding complications increased in elective-PCI patients treated with abciximab (RR: 2.94, 95% CI: 1.68-5.13, P<0.001, whereas major bleedings rate was similar (RR: 0.83, 95% CI: 0.27-2.57. CONCLUSIONS: Concomitant dosing of abciximab and thienopyridines provides no additional benefit among diabetic patients who underwent PCI; this conclusion, though, needs further confirmation in larger studies.

  8. The noncompetitive blocker ( sup 3 H)chlorpromazine labels three amino acids of the acetylcholine receptor gamma subunit: Implications for the alpha-helical organization of regions MII and for the structure of the ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Revah, F.; Galzi, J.L.; Giraudat, J.; Haumont, P.Y.; Lederer, F.; Changeux, J.P. (Centre National de la Recherche Scientifique, Paris (France))

    1990-06-01

    Labeling studies of Torpedo marmorata nicotinic acetylcholine receptor with the noncompetitive channel blocker ({sup 3}H)chlorpromazine have led to the initial identification of amino acids plausibly participating to the walls of the ion channel on the alpha, beta, and delta subunits. We report here results obtained with the gamma subunit, which bring additional information on the structure of the channel. After photolabeling of the membrane-bound receptor under equilibrium conditions in the presence of agonist and with or without phencyclidine (a specific ligand for the high-affinity site for noncompetitive blockers), the purified labeled gamma subunit was digested with trypsin, and the resulting fragments were fractionated by HPLC. Sequence analysis of peptide mixtures containing various amounts of highly hydrophobic fragments showed that three amino acids are labeled by ({sup 3}H)chlorpromazine in a phencyclidine-sensitive manner: Thr-253, Ser-257, and Leu-260. These residues all belong to the hydrophobic and putative transmembrane region MII of the gamma subunit. Their distribution along the sequence is consistent with an alpha-helical organization of this segment. The ({sup 3}H)chlorpromazine-labeled amino acids are conserved at homologous positions in the known sequences of other ligand-gated ion channels and may, thus, play a critical role in ion-transport mechanisms.

  9. In silico optimization of pharmacokinetic properties and receptor binding affinity simultaneously: a 'parallel progression approach to drug design' applied to β-blockers.

    Science.gov (United States)

    Advani, Poonam; Joseph, Blessy; Ambre, Premlata; Pissurlenkar, Raghuvir; Khedkar, Vijay; Iyer, Krishna; Gabhe, Satish; Iyer, Radhakrishnan P; Coutinho, Evans

    2016-01-01

    The present work exploits the potential of in silico approaches for minimizing attrition of leads in the later stages of drug development. We propose a theoretical approach, wherein 'parallel' information is generated to simultaneously optimize the pharmacokinetics (PK) and pharmacodynamics (PD) of lead candidates. β-blockers, though in use for many years, have suboptimal PKs; hence are an ideal test series for the 'parallel progression approach'. This approach utilizes molecular modeling tools viz. hologram quantitative structure activity relationships, homology modeling, docking, predictive metabolism, and toxicity models. Validated models have been developed for PK parameters such as volume of distribution (log Vd) and clearance (log Cl), which together influence the half-life (t1/2) of a drug. Simultaneously, models for PD in terms of inhibition constant pKi have been developed. Thus, PK and PD properties of β-blockers were concurrently analyzed and after iterative cycling, modifications were proposed that lead to compounds with optimized PK and PD. We report some of the resultant re-engineered β-blockers with improved half-lives and pKi values comparable with marketed β-blockers. These were further analyzed by the docking studies to evaluate their binding poses. Finally, metabolic and toxicological assessment of these molecules was done through in silico methods. The strategy proposed herein has potential universal applicability, and can be used in any drug discovery scenario; provided that the data used is consistent in terms of experimental conditions, endpoints, and methods employed. Thus the 'parallel progression approach' helps to simultaneously fine-tune various properties of the drug and would be an invaluable tool during the drug development process.

  10. The roles of beta-adrenergic receptors in tumorigenesis and the possible use of beta-adrenergic blockers for cancer treatment: possible genetic and cell-signaling mechanisms.

    Science.gov (United States)

    Quốc Lu'o'ng, Khanh Vinh; Nguyễn, Lan Thi Hoàng

    2012-01-01

    Cancer is the leading cause of death in the USA, and the incidence of cancer increases dramatically with age. Beta-adrenergic blockers appear to have a beneficial clinical effect in cancer patients. In this paper, we review the evidence of an association between β-adrenergic blockade and cancer. Genetic studies have provided the opportunity to determine which proteins link β-adrenergic blockade to cancer pathology. In particular, this link involves the major histocompatibility complex class II molecules, the renin-angiotensin system, transcription factor nuclear factor-kappa-light-chain-enhancer of activated B cells, poly(ADP-ribose) polymerase-1, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate oxidase. Beta-adrenergic blockers also exert anticancer effects through non-genomic factors, including matrix metalloproteinase, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase-2, oxidative stress, and nitric oxide synthase. In conclusion, β-adrenergic blockade may play a beneficial role in cancer treatment. Additional investigations that examine β-adrenergic blockers as cancer therapeutics are required to further elucidate this role.

  11. Marine Bivalve Cellular Responses to Beta Blocker Exposures

    Science.gov (United States)

    β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent binding of agonists such as catecholamines to β adrenoceptors. In the absence of agonist induced activation of the receptor, adenylate cyclase is not activated whi...

  12. Occurrence and fate of the angiotensin II receptor antagonist transformation product valsartan acid in the water cycle--a comparative study with selected β-blockers and the persistent anthropogenic wastewater indicators carbamazepine and acesulfame.

    Science.gov (United States)

    Nödler, Karsten; Hillebrand, Olav; Idzik, Krzysztof; Strathmann, Martin; Schiperski, Ferry; Zirlewagen, Johannes; Licha, Tobias

    2013-11-01

    The substantial transformation of the angiotensin II receptor antagonist valsartan to the transformation product 2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-carboxylic acid (referred to as valsartan acid) during the activated sludge process was demonstrated in the literature and confirmed in the here presented study. However, there was a severe lack of knowledge regarding the occurrence and fate of this compound in surface water and its behavior during drinking water treatment. In this work a comparative study on the occurrence and persistency of valsartan acid, three frequently used β-blockers (metoprolol, atenolol, and sotalol), atenolol acid (one significant transformation product of atenolol and metoprolol), and the two widely distributed persistent anthropogenic wastewater indicators carbamazepine and acesulfame in raw sewage, treated wastewater, surface water, groundwater, and tap water is presented. Median concentrations of valsartan acid in the analyzed matrices were 101, 1,310, 69, waters valsartan acid was found just as relevant as the analyzed β-blockers and the anticonvulsant carbamazepine. Regarding its persistency in surface waters it was comparable to carbamazepine and acesulfame. Furthermore, removal of valsartan acid during bank filtration was poor, which demonstrated the relevance of this compound for drinking water suppliers. Regarding drinking water treatment (Muelheim Process) the compound was resistant to ozonation but effectively eliminated (≥90%) by subsequent activated carbon filtration. However, without applying activated carbon filtration the compound may enter the drinking water distribution system as it was demonstrated for Berlin tap water. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. The alpha/beta-adrenergic receptor blocker arotinolol activates the thermogenesis of brown adipose tissue in monosodium-L-glutamate-induced obese mice.

    Science.gov (United States)

    Yoshida, T; Sakane, N; Wakabayashi, Y; Yoshioka, K; Umekawa, T; Kondo, M

    1994-05-01

    We have found previously that arotinolol, an alpha/beta-adrenergic blocker, increases blood flow in brown adipose tissue (BAT) in a similar extent as BRL 26830A, a beta 3-adrenoceptor agonist. We tested the hypothesis that arotinolol activates thermogenesis in BAT, leading to weight loss in monosodium-L-glutamate-induced (MSG-induced) obese mice and saline-treated controls. Six weeks of standard animal feed (CE-2) containing arotinolol hydrochloride (350 mg/kg CE-2), which reduced mean blood pressure in MSG-treated mice, significantly increased the mitochondrial protein content in BAT, and activated the specific and total binding of guanosine-5'-diphosphate (GDP) in BAT mitochondria, leading to a reduction of obesity in both MSG- and saline-treated mice vs. the control groups fed with CE-2 diet alone. However, six weeks of CE-2 diet containing propranolol hydrochloride (525 mg/kg CE-2) a non-selective beta-blocker, markedly reduced the specific and total binding of GDP in BAT mitochondria, leading to weight gain in both MSG- and saline-treated mice. These findings support the hypothesis, that arotinolol activates BAT thermogenesis, leading to weight loss.

  15. Impact of abciximab in elderly patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention: an observational registry study

    DEFF Research Database (Denmark)

    Iversen, Allan Z; Galatius, Soeren; Haahr-Pedersen, Sune Ammentorp

    2011-01-01

    BACKGROUND: An increasing proportion of patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) are classified as elderly (aged =70 years). The glycoprotein IIb/IIIa inhibitor abciximab is known to reduce adverse outcomes in patients aged

  16. Pooled Analysis Comparing the Efficacy of Intracoronary Versus Intravenous Abciximab in Smokers Versus Nonsmokers Undergoing Primary Percutaneous Coronary Revascularization for Acute ST-Elevation Myocardial Infarction

    DEFF Research Database (Denmark)

    Piccolo, Raffaele; Galasso, Gennaro; Eitel, Ingo

    2016-01-01

    Cigarette smokers with ST-segment elevation myocardial infarction (STEMI) may present different response to potent antithrombotic therapy compared to nonsmokers. We assessed the impact of smoking status and intracoronary abciximab in patients with STEMI undergoing primary percutaneous coronary in...

  17. Discovery of novel, potent and low-toxicity angiotensin II receptor type 1 (AT1) blockers: Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazoles with a chiral center.

    Science.gov (United States)

    Han, Xiao-Feng; He, Xing; Wang, Miao; Xu, Di; Hao, Li-Ping; Liang, Ai-Hua; Zhang, Jun; Zhou, Zhi-Ming

    2015-10-20

    Novel angiotensin II receptor type 1 (AT1) blockers bearing 6-substituted carbamoyl benzimidazoles with a chiral center were designed and synthesized as the first step to develop new antihypertensive agents and understand their pharmacodynamic and pharmacokinetic properties. The newly synthesized compounds were tested for their potential ability to displace [(125)I] Sar(1) Ile(8)-Ang II, which was specifically bound to human AT1 receptor. Radioligand binding assays revealed nanomolar affinity in several compounds under study. The IC50 values of nine ligands were higher than those of Losartan. The screening of decreased blood pressure in spontaneous hypertensive rats displayed that compound 8S (IC₅₀ = 5.0 nM) was equipotent with Losartan, whereas compounds 13R (IC₅₀ = 7.3 nM), 14R (IC₅₀ = 6.3 nM), and 14S (IC₅₀ = 3.5 nM) were slightly ahead of Losartan, and the most significant activity was demonstrated by compound 8R (IC₅₀ = 1.1 nM). Candidate 8R was identified for its excellent efficacy in antihypertension and fairly low toxicity based on plasma analyses, toxicology studies, and chronic oral tests. Finally, compound 8R exhibited strong and multiple interactions with target active sites of the theoretical AT1 receptor model in docking study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Abciximab in the management of acute myocardial infarction with ST-segment elevation: evidence-based treatment, current clinical use, and future perspectives

    Directory of Open Access Journals (Sweden)

    Dziewierz A

    2014-07-01

    Full Text Available Artur Dziewierz,1 Tomasz Rakowski,1 Dariusz Dudek2 12nd Department of Cardiology, Jagiellonian University Medical College, Krakow, Poland; 2Department of Interventional Cardiology, Jagiellonian University Medical College, Krakow, Poland Abstract: Introduction of antiplatelet agents has contributed substantially to improve the outcome of patients with acute coronary syndromes. Meta-analysis of the studies on abciximab administration during primary percutaneous coronary intervention (PCI for acute ST-segment elevation myocardial infarction (STEMI has clearly confirmed the mortality benefit associated with intravenous bolus and infusion of abciximab compared to placebo. Recently, introduction of new oral P2Y12 inhibitors (prasugrel, ticagrelor, with a faster and more pronounced antiplatelet effect, have decreased the use of abciximab even in patients with STEMI. However, recent studies have shown a delayed onset of antiplatelet effect of new oral antiplatelet drugs in the setting of STEMI, especially in patients with hemodynamic compromise. Thus, the use of abciximab as an intravenous agent should be strongly considered when oral P2Y12 inhibitors might fail or cannot be given before primary PCI for STEMI. An additional benefit of abciximab administration was reported when abciximab was given early, before primary PCI, compared to typical periprocedural use. To the contrary, no clear clinical benefit was confirmed for intracoronary administration of abciximab compared with intravenous administration. Future studies should focus on the role of abciximab given on top of new oral P2Y12 inhibitor (prasugrel, ticagrelor or used as an alternative to an intravenous P2Y12 inhibitor (cangrelor. Undoubtedly, the results of these studies will change everyday practice of STEMI treatment. Keywords: glycoprotein IIb/IIIa inhibitors, acute myocardial infarction, percutaneous coronary intervention

  19. The relative safety and efficacy of abciximab and eptifibatide in patients undergoing primary percutaneous coronary intervention: insights from a large regional registry of contemporary percutaneous coronary intervention.

    Science.gov (United States)

    Gurm, Hitinder S; Smith, Dean E; Collins, J Stewart; Share, David; Riba, Arthur; Carter, Andrew J; LaLonde, Thomas; Kline-Rogers, Eva; O'Donnell, Michael; Changezi, Hameem; Zughaib, Marcel; Safian, Robert; Moscucci, Mauro

    2008-02-05

    This study sought to assess whether the use of eptifibatide instead of abciximab is associated with a difference in outcomes of patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Pooled data from randomized controlled trials suggest that the use of abciximab may be associated with a survival advantage in patients undergoing primary PCI for acute STEMI. However, a large proportion of patients in the community are treated with eptifibatide, an agent that shares some but not all pharmacological properties with abciximab. We evaluated the outcomes of 3,541 patients who underwent primary PCI for STEMI from October 2002 to July 2006 in a large regional consortium and who were treated with abciximab (n = 729) or with eptifibatide (n = 2,812). There was no difference in the incidence of in-hospital death (4.1% with abciximab vs. 3.5% with eptifibatide, p = 0.39), recurrent myocardial infarction (0.8% vs. 1.2%, p = 0.42), or stroke/transient ischemic attack (0.7% vs. 0.6%, p = 0.80). There was no difference in the need for blood transfusion (12.4% vs. 11.7%, p = 0.61), whereas there was a greater incidence of gastrointestinal bleeding with abciximab (4.8% vs. 2.8%, p = 0.01). In parsimonious risk-adjusted models, no significant difference between abciximab and eptifibatide was observed with respect to any of the outcomes measures. Currently, eptifibatide is used as the adjunct antiplatelet agent in the majority of patients undergoing primary PCI. There is no apparent difference in early outcomes of patients treated with eptifibatide compared with patients treated with abciximab.

  20. Improved clinical outcomes with intracoronary compared to intravenous abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a systematic review and meta-analysis

    DEFF Research Database (Denmark)

    Hansen, Peter Riis; Iversen, Allan; Abdulla, Jawdat

    2010-01-01

    Intracoronary (IC) administration of abciximab may increase local drug levels by several orders of magnitude compared to intravenous (IV) treatment and may improve clinical outcomes in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). In the absence...... of results from large multicenter, randomized trials, we performed a systematic review and meta-analysis of available studies comparing IC to IV abciximab in these patients....

  1. 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.

  2. Procedural and clinical outcomes after use of the glycoprotein IIb/IIIa inhibitor abciximab for saphenous vein graft interventions

    Energy Technology Data Exchange (ETDEWEB)

    Harskamp, Ralf E., E-mail: r.e.harskamp@gmail.com [Academic Medical Center–University of Amsterdam, Amsterdam (Netherlands); VU University Medical Center, Amsterdam (Netherlands); Duke Clinical Research Institute, Durham, NC (United States); Hoedemaker, Niels [Academic Medical Center–University of Amsterdam, Amsterdam (Netherlands); Newby, L. Kristin [Duke Clinical Research Institute, Durham, NC (United States); Woudstra, Pier; Grundeken, Maik J.; Beijk, Marcel A.; Piek, Jan J.; Tijssen, Jan G. [Academic Medical Center–University of Amsterdam, Amsterdam (Netherlands); Mehta, Rajendra H. [Duke Clinical Research Institute, Durham, NC (United States); Winter, Robbert J. de [Academic Medical Center–University of Amsterdam, Amsterdam (Netherlands)

    2016-01-15

    Background: Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) poses a high-risk for distal coronary thromboembolic events. Glycoprotein IIb/IIIa inhibitors are frequently used in hope of reducing the impact of this, although the safety and efficacy of these drugs to improve outcomes in this setting are understudied. Methods: Patients were included if they had prior coronary artery bypass surgery and subsequently underwent PCI of ≥ 1 SVG graft at a Dutch academic center between 1997 and 2008. These patients were matched 1:1 based on peri-procedural use of abciximab using a propensity-score matching algorithm based on 17 variables. Conditional logistic regression and Cox regression stratified on matched pairs were performed to evaluate the association between abciximab use and MACCE (the composite measure of mortality, myocardial infarction, stroke and repeat revascularization) at 30 days and up to 1 year. Results: The composite of 30-day MACCE occurred in 18 patients (15.3%) in the abciximab group and 16 patients (13.6%) in the propensity matched control group (OR: 1.13, 95% CI: 0.57–2.21, p = 0.73). At 1-year follow-up, MACCE rates were also similar (32.5% vs. 33.9%, HR: 0.97, 95% CI: 0.59–1.59). Major bleeding (BARC types 3a–c) was higher in the abciximab group (11.9% vs. 4.2%, OR: 2.80, 95% CI: 1.01–7.77). Ischemic outcomes did not differ among patients with acute coronary syndromes. Conclusion: The use of intravenous abciximab was not associated with improved clinical outcomes up to 1-year among patients undergoing SVG PCI, but was related to more bleeding. - Highlights: • PCI of SVG poses a high-risk for distal coronary thromboembolic events. • Glycoprotein IIb/IIIa inhibitors are frequently used in an attempt to reduce this risk. • We evaluated the safety and efficacy of abciximab (a glycoprotein IIb/IIIa inhibitor) using a propensity-score matched analysis of 236 patients at a large academic medical center. • Thirty

  3. Off-target effects of glycoprotein IIb/IIIa receptor inhibitors

    NARCIS (Netherlands)

    Ostrowska, M.; Adamski, P.; Kozinski, M.; Navarese, E.P.; Fabiszak, T.; Grzesk, G.; Paciorek, P.; Kubica, J.

    2014-01-01

    Soon after identification of the platelet membrane glycoprotein (GP) IIb/IIIa, it has become a target of antiplatelet therapy. There are 3 intravenous GP IIb/IIIa receptor inhibitors, namely- eptifibatide, tirofiban and abciximab, used in the contemporary clinical practice, particularly in patients

  4. [Perioperative beta-blockers. Part one: fundamentals].

    Science.gov (United States)

    Piriou, V; Aouifi, A; Lehot, J J

    2000-07-01

    To review the pharmacologic and pathophysiologic information necessary to prescribe beta-blockers (BB) in perioperative medicine. Manual retrieval and electronic research of the literature using MEDLINE (key-words: anesthesia and beta- blocker; surgery and beta-blocker). Cardioselective BB inhibit preferentially beta-1 receptors, inducing a decrease in heart rate and cardiac inotropism leading to reduction of oxygen myocardial consumption. Non-cardioselective BB inhibit also beta-2 receptors, increasing bronchial and peripheral vascular resistances and uterine contractions. However, some BB are also vasodilators (carvedilol, celiprolol, labetalol). Contraindications to BB result logically from their pharmacological effects. Treatment with BB increases membrane beta-receptor density; this explains sympathetic overactivity observed during weaning of treatment. Since the discovery of propranolol in 1964, the use of BB has been controversial in anesthesia. Formerly, the adverse effects of partial sympatholysis during anesthesia and surgery were feared. However, since 1973, experimental and clinical data have suggested a protective hemodynamic effect. Continued administration of BB up to the time of anesthesia has been encouraged except in patients with signs of intolerance such as hypotension or excessive bradycardia.

  5. Angiotensin AT1-receptor blockers and cerebrovascular protection: do they actually have a cutting edge over angiotensin-converting enzyme inhibitors?

    DEFF Research Database (Denmark)

    Oprisiu-Fournier, Roxana; Faure, Sébastien; Mazouz, Hakim

    2009-01-01

    First, an update of the vascular systemic and tissue renin-angiotensin-aldosterone system is provided to explain how it is regulated at the systemic and tissue levels, and how many angiotensin peptides and receptors can be modulated by the various antihypertensive drugs. Second, experimental data...... AT2 receptors are overexpressed) or by directly increasing neuronal resistance to anoxia. Third, we review most of the large primary and secondary stroke prevention trials as well as the ACCESS acute stroke trial in which antihypertensive drugs were evaluated. With the exception of the secondary...

  6. Deterioration of kidney function by the (pro)renin receptor blocker handle region peptide in aliskiren-treated diabetic transgenic (mRen2)27 rats

    NARCIS (Netherlands)

    L. te Riet (Luuk); M.M. van den Heuvel (Mieke); C.J. Peutz-Kootstra (Carine); J.H.M. Esch, van (Joep); R. van Veghel (Richard); I.M. Garrelds (Ingrid); U. Musterd-Bhaggoe (Usha); A.M.B. Bouhuizen (Angelique); F.P.J. Leijten (Frank); A.H.J. Danser (Jan); W.W. Batenburg (Wendy)

    2014-01-01

    textabstractDual renin-angiotensin system (RAS) blockade in diabetic nephropathy is no longer feasible because of the profit/side effect imbalance. (Pro)renin receptor [(P)RR] blockade with handle region peptide (HRP) has been reported to exert beneficial effects in various diabetic models in a

  7. Intracoronary Versus Intravenous Administration of Abciximab in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention With Thrombus Aspiration The Comparison of Intracoronary Versus Intravenous Abciximab Administration During Emergency Reperfusion of ST-Segment Elevation Myocardial Infarction (CICERO) Trial

    NARCIS (Netherlands)

    Gu, Youlan L.; Kampinga, Marthe A.; Wieringa, Wouter G.; Fokkema, Marieke L.; Nijsten, Maarten W.; Hillege, Hans L.; van den Heuvel, Ad F. M.; Tan, Eng-Shiong; Pundziute, Gabija; van der Werf, Rik; Guyomi, Siyrous Hoseyni; van der Horst, Iwan C. C.; Zijlstra, Felix; de Smet, Bart J. G. L.

    2010-01-01

    Background-Administration of the glycoprotein IIb/IIIa inhibitor abciximab is an effective adjunctive treatment strategy during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Although small-scale studies have suggested beneficial effects of intracoronary

  8. Anti-Fibrotic Effect of Losartan, an Angiotensin II Receptor Blocker, Is Mediated through Inhibition of ER Stress via Up-Regulation of SIRT1, Followed by Induction of HO-1 and Thioredoxin.

    Science.gov (United States)

    Kim, Hyosang; Baek, Chung Hee; Lee, Raymond Bok; Chang, Jai Won; Yang, Won Seok; Lee, Sang Koo

    2017-01-31

    Endoplasmic reticulum (ER) stress is increasingly identified as modulator of fibrosis. Losartan, an angiotensin II receptor blocker, has been widely used as the first choice of treatment in chronic renal diseases. We postulated that anti-fibrotic effect of losartan is mediated through inhibition of ER stress via SIRT1 (silent mating type information regulation 2 homolog 1) hemeoxygenase-1 (HO-1)/thioredoxin pathway. Renal tubular cells, tunicamycin (TM)-induced ER stress, and unilateral ureteral obstruction (UUO) mouse model were used. Expression of ER stress was assessed by Western blot analysis and immunohistochemical stain. ER stress was induced by chemical ER stress inducer, tunicamycin, and non-chemical inducers such as TGF-β, angiotensin II, high glucose, and albumin. Losartan suppressed the TM-induced ER stress, as shown by inhibition of TM-induced expression of GRP78 (glucose related protein 78) and p-eIF2α (phosphospecific-eukaryotic translation initiation factor-2α), through up-regulation of SIRT1 via HO-1 and thioredoxin. Losartan also suppressed the ER stress by non-chemical inducers. In both animal models, losartan reduced the tubular expression of GRP78, which were abolished by pretreatment with sirtinol (SIRT1 inhibitor). Sirtinol also blocked the inhibitory effect of losartan on the UUO-induced renal fibrosis. These findings provide new insights into renoprotective effects of losartan and suggest that SIRT1, HO-1, and thioredoxin may be potential pharmacological targets in kidney diseases under excessive ER stress condition.

  9. Redefining beta-blocker use in hypertension: selecting the right beta-blocker and the right patient.

    Science.gov (United States)

    Mann, Samuel J

    2017-01-01

    Randomized controlled trials have concluded that the cardiovascular outcome of first-step treatment of hypertension with traditional vasoconstricting beta-blockers is inferior to treatment with other antihypertensive drug classes. Beta-blocker use is also associated with undesirable side effects. Consequently, some recent guidelines consider beta-blockers an inferior option for first-step treatment of hypertension. Despite this, beta-blockers are still widely prescribed, and likely overused, in the management of hypertension. It is the contention of this perspective that beta-blockers do have an important role in treating hypertension, but their use needs to be much better targeted, by better identification of both the right patient and the right beta-blocker. Identifying the right patient involves consideration of underlying mechanisms of hypertension. In the absence of comorbidities for which a beta-blocker is indicated, beta-blockers would not seem to be the preferred treatment for patients with either sodium/volume-mediated hypertension, for which they are usually ineffective, or for those with renin-angiotensin system-mediated hypertension, for which angiotensin-converting enzyme inhibitors and angiotensin receptor blockers provide equal antihypertensive efficacy with evidence of better outcome and fewer adverse effects. Beta-blockers would instead appear to be best suited for patients with sympathetically driven, that is, neurogenic, hypertension, whether as a first-step drug, such as in patients with hypertension in the acute post-stroke period, in so-called "hyperkinetic" patients, and in patients with labile hypertension, or as an add-on drug in patients with resistant hypertension. In choosing among the beta-blockers, combined alpha/beta-blockade offers advantages over beta-blocker monotherapy and merits greater clinical and research attention. Finally, unreliable bioavailability greatly interferes with the effectiveness of lipophilic, but not

  10. [Beta-blocker intoxication].

    Science.gov (United States)

    Joye, F

    2000-05-20

    Beta-blocker intoxication is not frequent but can produce particularly severe or fatal conditions which must not be underestimated. Severity of beta-blocker intoxication varies from one compound to another. The more toxic drugs are propranolol, sotalol, oxprenolol, metoprolol, atenolol, acebutolol, labetalol, and carvedilol. Besides the drug type, history taking can provide a precise assessment of risk, particularly important in when elderly patients with a cardiovascular history have taken more than 20 tablets, when emergency care is provided late, and when other cardiotoxic or psychotoxic drugs have been coingested. The diagnosis of beta-blocker intoxication must be suspected in any case associating hypotension and bradycardia. The main cardiovascular complications are cardiogenic shock, atrio-ventricular conduction disorders, and obviously life-threatening ventricular arrhythmia with cardiac arrest. Centrally induced respiratory arrest is a rare but dreadful consequence which can occur suddenly even without hemodynamic failure. Neurologic toxicity is mainly expressed by consciousness disorders and more sporadically by seizures. Laboratory tests show variable serum potassium, lactic acidosis, hypoxia-hypercapnia resulting from hypoventilation, and rarely hypoglycemia. The ECG should be recorded early because electrocardiographic signs usually appear before clinical signs and QRS enlargement is a factor predictive of severe ventricular arrhythmia. The patient must be placed in an intensive care unit for continuous multiparametric monitoring. Besides gastric evacuation and symptomatic measures, treatment essentially requires glucagon for its positive inotropic effect after high intravenous doses. If glucagon infusion is ineffective or unavailable, an alternative would be to use high doses of vasoactive agents, choosing isoproterenol or epinephrine as the first intention drugs.

  11. Investigation of interaction of human platelet membrane components with anticoagulant drugs Abciximab and Eptifibatide

    Directory of Open Access Journals (Sweden)

    Ewa Gorodkiewicz

    2010-04-01

    Full Text Available Abciximab (Abci and eptifibatide (Epti are antiaggregate drugs which may reduce thrombotic complications inacute coronary syndromes. The aim of this work was the investigation of the interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and Abci or Epti, and the influence of these drugs on the phospholipid ratio in the plateletmembrane. The interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and antiaggregate drugs were investigatedusing the Surface Plasmon Resonance Imaging technique (SPRI. Phospholipids phosphatidylinositol (PI, phosphatidylserine(PS, phosphatidylethanolamine (PE, phosphatidylcholine (PC and sphingomyelin (SM were first immobilizedonto the gold chip surface. The phospholipid ratio in the platelet membrane was determined by the HPLC. Only PI,PS, PE and PC were determined. Human platelets treated 'in vitro' with Abci or Epti exhibit changes in the phospholipidratio in the platelet membrane. The ratio of PS decreases and PC rises. The SPRI distinctly shows interactions between phospholipidsand glycoprotein GPIIb/IIIa, and between the phospholipid-glycoprotein GPIIb/IIIa complex and Abci or Epti.The interaction between phospholipids and glycoprotein GPIIb/IIIa is growing in the sequence: PI<

  12. Investigation of interaction of human platelet membrane components with anticoagulant drugs Abciximab and Eptifibatide.

    Directory of Open Access Journals (Sweden)

    Anna Sankiewicz

    2011-04-01

    Full Text Available Abciximab (Abci and eptifibatide (Epti are antiaggregate drugs which may reduce thrombotic complications in acute coronary syndromes. The aim of this work was the investigation of the interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and Abci or Epti, and the influence of these drugs on the phospholipid ratio in the platelet membrane. The interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and antiaggregate drugs were investigated using the Surface Plasmon Resonance Imaging technique (SPRI. Phospholipids phosphatidylinositol (PI, phosphatidylserine (PS, phosphatidylethanolamine (PE, phosphatidylcholine (PC and sphingomyelin (SM were first immobilized onto the gold chip surface. The phospholipid ratio in the platelet membrane was determined by the HPLC. Only PI, PS, PE and PC were determined. Human platelets treated 'in vitro' with Abci or Epti exhibit changes in the phospholipid ratio in the platelet membrane. The ratio of PS decreases and PC rises. The SPRI distinctly shows interactions between phospholipids and glycoprotein GPIIb/IIIa, and between the phospholipid-glycoprotein GPIIb/IIIa complex and Abci or Epti. The interaction between phospholipids and glycoprotein GPIIb/IIIa is growing in the sequence: PI

  13. Comparison between Intracoronary Abciximab and Intravenous Eptifibatide Administration during Primary Percutaneous Coronary Intervention of Acute ST-Segment Elevation Myocardial Infarction.

    Science.gov (United States)

    Namazi, Mohammad Hasan; Safi, Morteza; Vakili, Hosein; Saadat, Habibollah; Karimi, Esfandiar; Bagheri, Ramin Khameneh

    2013-07-01

    Administration of glycoprotein IIb/IIIa inhibitors is an effective adjunctive treatment strategy during primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). Recent data suggest that an intracoronary administration of these drugs can increase the efficacy of PPCI. This study was done to find any potential difference in terms of efficacy of administering intracoronary Abciximab vs. intravenous Eptifibatide in primary PPCI. A total of 40 STEMI patients who underwent PPCI within 12 hours of symptom onset were randomized to either an intracoronary Abciximab (0.25 μg/kg) bolus or two boluses of intravenous Eptifibatide (0.180 μg/kg) each 10 minutes. The primary end points were enzymatic infarct size, myocardial reperfusion measured as ST-segment resolution (STR), and post-procedural thrombolysis in myocardial infarction (TIMI) grade flow of the infarct-related artery. The secondary end points were intra-procedural adverse effect (arrhythmia) and no-reflow phenomenon, in-hospital mortality, reinfarction, hemorrhage, and post-procedural global systolic function. Post-procedural TIMI grade 3 flow was achieved in 95% and 90% of the intracoronary Abciximab and intravenous Eptifibatide groups, respectively (p value = 0.61). The infarct size, as assessed by the area under the curve of creatine phosphokinase-MB in the first 48 hours after PPCI (μmol/L/hr), was similar between the intracoronary Abciximab and intravenous Eptifibatide groups: 6591 (interquartile range [IQR], 3006.0 to 11112.0) versus 7,294 (IQR, 3795.5 to 11803.5); p value = 0.59. Complete STR was achieved in 55% and 45% of the intracoronary Abciximab and intravenous Eptifibatide groups, respectively (p value = 0.87). No deaths, urgent revascularizations, reinfarctions, or TIMI major bleeding events were observed in either group. The intracoronary administration of Abciximab was not superior to the intravenous administration of Eptifibatide in the STEMI

  14. Comparison between Intracoronary Abciximab and Intravenous Eptifibatide Administration during Primary Percutaneous Coronary Intervention of Acute ST-Segment Elevation Myocardial Infarction

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    MohammadHasan Namazi

    2015-10-01

    Full Text Available Background: Administration of glycoprotein IIb/IIIa inhibitors is an effective adjunctive treatment strategy during primary percutaneous coronary intervention (PPCI for ST-segment elevation myocardial infarction (STEMI. Recent data suggest that an intracoronary administration of these drugs can increase the efficacy of PPCI. This study was done to find any potential difference in terms of efficacy of administering intracoronary Abciximab vs. intravenous Eptifibatide in primary PPCI.Methods: A total of 40 STEMI patients who underwent PPCI within 12 hours of symptom onset were randomized to either an intracoronary Abciximab (0.25 µg/kg bolus or two boluses of intravenous Eptifibatide (0.180 µg/kg each 10 minutes. The primary end points were enzymatic infarct size, myocardial reperfusion measured as ST-segment resolution (STR, and post-procedural thrombolysis in myocardial infarction (TIMI grade flow of the infarct-related artery. The secondary end points were intra-procedural adverse effect (arrhythmia and no-reflow phenomenon, in-hospital mortality, reinfarction, hemorrhage, and post-procedural global systolic function.Results: Post-procedural TIMI grade 3 flow was achieved in 95% and 90% of the intracoronary Abciximab and intravenous Eptifibatide groups, respectively (p value = 0.61. The infarct size, as assessed by the area under the curve of creatine phosphokinase-MB in the first 48 hours after PPCI (µmol/L/hr , was similar between the intracoronary Abciximab and intravenous Eptifibatide groups: 6591 (interquartile range [IQR], 3006.0 to 11112.0 versus 7,294 (IQR, 3795.5 to 11803.5; p value = 0.59. Complete STR was achieved in 55% and 45% of the intracoronary Abciximab and intravenous Eptifibatide groups, respectively (p value = 0.87. No deaths, urgent revascularizations, reinfarctions, or TIMI major bleeding events were observed in either group.Conclusion: The intracoronary administration of Abciximab was not superior to the intravenous

  15. Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer.

    Science.gov (United States)

    Watkins, Jack L; Thaker, Premal H; Nick, Alpa M; Ramondetta, Lois M; Kumar, Sanjeev; Urbauer, Diana L; Matsuo, Koji; Squires, Kathryn C; Coleman, Robert L; Lutgendorf, Susan K; Ramirez, Pedro T; Sood, Anil K

    2015-10-01

    Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta-adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]). A multicenter review of 1425 women with histopathologically confirmed EOC was performed. Comparisons were made between patients with documented beta-blocker use during chemotherapy and those without beta-blocker use. The median age of patients in the current study was 63 years (range, 21-93 years). The sample included 269 patients who received beta-blockers. Of those, 193 (71.7%) were receiving beta-1-adrenergic receptor selective agents, and the remaining patients were receiving nonselective beta antagonists. The primary indication for beta-blocker use was hypertension but also included arrhythmia and postmyocardial infarction management. For patients receiving any beta-blocker, the median overall survival (OS) was 47.8 months versus 42 months for nonusers (P =.04). The median OS based on beta-blocker receptor selectivity was 94.9 months for those receiving nonselective beta-blockers versus 38 months for those receiving beta-1-adrenergic receptor selective agents (Pbeta-blocker compared with nonusers (38.2 months vs 90 months; Pbeta-blockers in patients with EOC was associated with longer OS. These findings may have implications for new therapeutic approaches. Cancer 2015;121:3435-43. © 2015 American Cancer Society. © 2015 American Cancer Society.

  16. Impact of abciximab in diabetic patients with acute coronary syndrome who undergo percutaneous coronary intervention: results from a high-volume, single-center registry

    DEFF Research Database (Denmark)

    Iversen, Allan; Haahr-Pedersen, Sune Ammentorp; Joens, Christian

    2011-01-01

    BACKGROUND: The prevalence of diabetes mellitus (DM) and ischemic heart disease is increasing. Moreover, patients with DM experiencing an acute coronary syndrome (ACS) have an increased risk of adverse outcomes after revascularization compared to non-diabetics. Data have suggested...... that the glycoprotein IIb/IIIa inhibitor abciximab might be more efficient in diabetics than in those without DM. METHODS AND RESULTS: We evaluated the effect of abciximab in patients with DM and ACS from our percutaneous coronary intervention (PCI) registry. Among 5,003 patients with ACS who underwent PCI, 629 had DM...

  17. Cannabinoid-1 receptor (CB1R) blockers as medicines: beyond obesity and cardiometabolic disorders to substance abuse/drug addiction with CB1R neutral antagonists.

    Science.gov (United States)

    Janero, David R

    2012-03-01

    Addiction to chemical substances with abuse potential presents medical needs largely unsolved by extant therapeutic strategies. Signal transmission through the cannabinoid-1 receptor (CB1R) in the central nervous system (CNS) modulates neurotransmitters/neuronal pathways contributing to the rewarding properties and hedonic effects of certain nondrug stimuli (e.g., food) and many prototypical addictive drugs, promoting excessive intake and its pathological consequences. Typical CB1R antagonists/inverse agonists reduce the rewarding effects and normalize behavioral phenotypes associated with food and abused drugs, but carry an unacceptable adverse-event profile that may reflect, at least partly, their intrinsic ability to alter basal homeostatic CB1R signaling in the CNS and elicit a negative efficacy response. Alternatively, peripherally biased CB1R inverse agonists with limited CNS permeability and putative CB1R neutral antagonists expressing modest (if any) inverse-agonist efficacy are garnering attention for treating obesity and related cardiometabolic complications with a potentially enhanced benefit-to-risk profile. This mini-review calls attention to the proposition that CB1R neutral antagonists offer attractive opportunities for pharmacotherapeutic exploitation in the substance abuse/drug addiction space, whereas the restricted CNS accessibility of peripherally biased CB1R inverse agonists circumscribes their therapeutic utility for this indication. The unique preclinical pharmacology, efficacy profiles, and reduced adverse-event risk of CB1R neutral antagonists make them worthy of translational study for their potential therapeutic application beyond obesity/cardiometabolic disease to include substance-abuse/drug-addiction disorders.

  18. 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. Sheps, ... can occur as a side effect of some beta blockers, especially the older ones, such as atenolol (Tenormin) ...

  19. Beta-blockers in hypertension.

    Science.gov (United States)

    Ram, C Venkata S

    2010-12-15

    Beta blockers have been used in the treatment of cardiovascular conditions for decades. Despite a long history and status as a guideline-recommended treatment option for hypertension, recent meta-analyses have brought into question whether β blockers are still an appropriate therapy given outcomes data from other antihypertensive drug classes. However, β blockers are a heterogenous class of agents with diverse pharmacologic and physiologic properties. Much of the unfavorable data revealed in the recent meta-analyses were gleaned from studies involving nonvasodilating, traditional β blockers, such as atenolol. However, findings with traditional β blockers may not be extrapolated to other members of the class, particularly those agents with vasodilatory activity. Vasodilatory β blockers (i.e., carvedilol and nebivolol) reduce blood pressure in large part through reducing systemic vascular resistance rather than by decreasing cardiac output, as is observed with traditional β blockers. Vasodilating ability may also ameliorate some of the concerns associated with traditional β blockade, such as the adverse effects on metabolic and lipid parameters, including an increased risk for new-onset diabetes. Furthermore, vasodilating ability is physiologically relevant and important in treating a condition with common co-morbidities involving metabolic and lipid abnormalities such as hypertension. In patients with hypertension and diabetes or coronary artery disease, vasodilating β blockers provide effective blood pressure control with neutral or beneficial effects on important parameters for the co-morbid disease. In conclusion, it is time for a reexamination of the clinical evidence for the use of β blockers in hypertension, recognizing that there are patients for whom β blockers, particularly those with vasodilatory actions, are an appropriate treatment option. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. 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.

  1. 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

    Directory of Open Access Journals (Sweden)

    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

  2. Short-term add-on therapy with angiotensin receptor blocker for end-stage inotrope-dependent heart failure patients: B-type natriuretic peptide reduction in a randomized clinical trial

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    Marcelo E. Ochiai

    2014-01-01

    Full Text Available OBJECTIVE: We aimed to evaluate angiotensin receptor blocker add-on therapy in patients with low cardiac output during decompensated heart failure. METHODS: We selected patients with decompensated heart failure, low cardiac output, dobutamine dependence, and an ejection fraction <0.45 who were receiving an angiotensin-converting enzyme inhibitor. The patients were randomized to losartan or placebo and underwent invasive hemodynamic and B-type natriuretic peptide measurements at baseline and on the seventh day after intervention. ClinicalTrials.gov: NCT01857999. RESULTS: We studied 10 patients in the losartan group and 11 patients in the placebo group. The patient characteristics were as follows: age 52.7 years, ejection fraction 21.3%, dobutamine infusion 8.5 mcg/kg.min, indexed systemic vascular resistance 1918.0 dynes.sec/cm5.m2, cardiac index 2.8 L/min.m2, and B-type natriuretic peptide 1,403 pg/mL. After 7 days of intervention, there was a 37.4% reduction in the B-type natriuretic peptide levels in the losartan group compared with an 11.9% increase in the placebo group (mean difference, -49.1%; 95% confidence interval: -88.1 to -9.8%, p = 0.018. No significant difference was observed in the hemodynamic measurements. CONCLUSION: Short-term add-on therapy with losartan reduced B-type natriuretic peptide levels in patients hospitalized for decompensated severe heart failure and low cardiac output with inotrope dependence.

  3. 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

  4. Clinical Impact of Selective and Non-selective Beta Blockers on Survival in Ovarian Cancer Patients

    Science.gov (United States)

    Watkins, Jack L.; Thaker, Premal H.; Nick, Alpa M.; Ramondetta, Lois M.; Kumar, Sanjeev; Urbauer, Diana L.; Matsuo, Koji; Squires, Kathryn; Lutgendorf, Susan K.; Ramirez, Pedro T.; Sood, Anil K.

    2015-01-01

    BACKGROUND Preclinical evidence suggests that sustained adrenergic activation can promote ovarian cancer growth and metastasis. We examined the impact of beta-adrenergic blockade on clinical outcome of women with epithelial ovarian, primary peritoneal or fallopian tube cancers (collectively, EOC). METHODS A multicenter review of 1,425 women with histopathologically confirmed EOC was performed. Comparisons were made between patients with documented beta blocker use during chemotherapy and those without beta blocker use. RESULTS The median age of patients in this study was 63 years (range, 21–93 years). The sample included 269 patients who received beta blockers. Of those, 193 (71.7%) were receiving beta-1 adrenergic receptor (ADRB1) selective agents, and the remaining patients were receiving non-selective beta antagonists. The primary indication for beta blocker use was hypertension but also included arrhythmia and post-myocardial infarction management. For patients receiving any beta blocker, the median overall survival (OS) was 47.8 months versus42 months (P = 0.04) for non-users. The median OS based on beta blocker receptor selectivity was 94.9 months for those receiving non-selective beta blockers versus 38 months for those receiving ADRB1 selective agents (P beta blocker had a longer median OS than non-users observed (38.2 vs 90 months, P beta blockers in epithelial ovarian cancer patients was associated with longer OS. These findings may have implications for new therapeutic approaches. PMID:26301456

  5. Adição de Bloqueador do receptor de angiotensina II na insuficiência cardíaca descompensada Adición de bloqueante del receptor de angiotensina II en la insuficiencia cardiaca descompensada Angiotensin II receptor blocker add-on therapy for low cardiac output in decompensated heart failure

    Directory of Open Access Journals (Sweden)

    Marcelo E. Ochiai

    2010-02-01

    pacientes internados por descompensación de la insuficiencia cardiaca y con empleo por más de 15 días de dobutamina, o una o más intentos sin éxito de retirada; dosis optimizada de IECA; y FEVI BACKGROUND: During heart failure (HF decompensation, an intense activation of the renin-angiotensin-aldosterone system occurs; however, the use of angiotensin-converting enzyme inhibitor (ACEI cannot block it completely. Otherwise, the addition of angiotensin II receptor blocker (ARB can be useful when the inotropic dependence occurs. We evaluated the efficacy of the ARB-ACEI association on dobutamine withdrawal in advanced decompensated HF. OBJECTIVE: To assess the efficacy of association angiotensin receptor blocker - angiotensin converting enzyme inhibitor to withdraw the intravenous inotropic support in decompensated severe heart failure. METHODS: In a case-control study (N = 24, we selected patients admitted at the hospital due to HF that had been using dobutamine for more than 15 days, with one or more unsuccessful drug withdrawal attempts; optimized dose of ACEI and ejection fraction (EF < 0.45. Then, the patients additionally received ARB (n=12 or not (control, n=12. The outcome was the successful dobutamine withdrawal, evaluated by logistic regression, with a p < 0.05. RESULTS: The EF was 0.25 and the age was 53 years, with a dobutamine dose of 10.7 μg/kg.min. The successful drug withdrawal was observed in 8 patients from the ARB group (67.7% and in 2 patients from the control group (16.7%. The odds ratio (OR was 10.0 (95%CI: 1.4 to 69.3; p = 0.02. The worsening in renal function was similar (ARB group: 42% vs. control group: 67%; p=0.129. CONCLUSION: In this pilot study, the ARB-ACEI association was associated with successful dobutamine withdrawal in advanced decompensated heart failure. The worsening in renal function was similar in both groups. Further studies are necessary to clarify the issue.

  6. The PFA-100R cannot detect blood group-dependent inhibition of platelet function by eptifibatide or abciximab at therapeutic plasma concentrations.

    Science.gov (United States)

    Feuring, M; Ruf, A; Schultz, A; Wehling, M

    2010-01-01

    Previous investigations revealed that AB0 blood groups are associated with divergent concentrations of several coagulation factors. Concentrations of von Willebrand factor (vWF) and factor VIII are lower in individuals with blood group 0 compared to subjects with blood group A, B or AB, which might in turn result in a reduced inhibition of platelet aggregation in individuals with blood group 0. The aim of the present in vitro investigation was to elucidate the impact of AB0 blood group-dependent vWF concentrations on eptifibatide and abciximab mediated inhibition of GPIIb/IIIa function. Platelet function was measured with the platelet function analyzer PFA-100(R) at baseline and at increasing concentrations of eptifibatide and abciximab. It was stratified for blood group 0 vs A. If measured with the collagen/ADP cartridge, blood group 0 was associated with a prolonged mean baseline closure time in comparison with blood group A (94.3 +/- 14.6 s vs. 74.6 +/- 9.9 s, p = 0.007) which was paralleled by reduced concentrations of vWF and factor VIII. In contrast, no statistically significant differences in closure times (167.4 +/- 83.9 s vs. 140.1 +/- 99.0 s, p = 0.562) could be found in the presence of eptifibatide (0.1 microg/ml). Higher concentrations of abciximab (1 microg/ml) than those of eptifibatide were needed to increase the closure times in both cartridges of the PFA-100, but at this concentration of abciximab differences in closure times could not be detected most probably due to higher variability at these drug concentrations. The PFA-100(R) is not suitable for monitoring abciximab or eptifibatide within the therapeutic concentration range because the highest concentrations where the PFA-100(R) had measurable closure times of below 300 s is much too low to lead to the necessary platelet inhibition and, consequently, does not resemble the in vivo situation.

  7. The comparative safety of abciximab versus eptifibatide in patients on dialysis undergoing percutaneous coronary intervention: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2).

    Science.gov (United States)

    Sukul, Devraj; Seth, Milan; Schreiber, Theodore; Hanzel, George; Khandelwal, Akshay; Cannon, Louis A; Lalonde, Thomas A; Gurm, Hitinder S

    2017-08-01

    We sought to evaluate the patterns of use and outcomes associated with eptifibatide and abciximab administration among dialysis patients who underwent percutaneous coronary intervention (PCI). Contraindicated medications are frequently administered to dialysis patients undergoing PCI often resulting in adverse outcomes. Eptifibatide is a glycoprotein IIb/IIIa inhibitor that is often used during PCI and is contraindicated in dialysis. We included dialysis patients who underwent PCI from January 2010 to September 2015 at 47 hospitals in Michigan. We compared outcomes between patients who received eptifibatide compared with abciximab. Both groups required concurrent treatment with unfractionated heparin only. In-hospital outcomes included repeat PCI, bleeding, major bleeding, need for transfusion, and death. Optimal full matching was used to adjust for non-random drug administration. Of 177 963 patients who underwent PCI, 4303 (2.4%) were on dialysis. Among those, 384 (8.9%) received eptifibatide and 100 (2.3%) received abciximab. Prior to matching, patients who received eptifibatide had higher pre-procedural hemoglobin levels (11.3 g/dL vs. 10.7 g/dL; P eptifibatide and abciximab including transfusion (aOR: 1.15; 95%CI: 0.55-2.40; P = 0.70), bleeding (1.47; 0.64-3.40; P = 0.36), major bleeding (4.68; 0.42-52.3; P = 0.21), repeat PCI (0.38; 0.03-4.23; P = 0.43), and death (1.53; 0.2-9.05; P = 0.64). Despite being contraindicated in dialysis, eptifibatide was used approximately 3.5 times more frequently than abciximab among dialysis patients undergoing PCI but was associated with similar in-hospital outcomes. © 2017, Wiley Periodicals, Inc.

  8. Beta-blockers for hypertension

    Science.gov (United States)

    Wiysonge, Charles S; Bradley, Hazel A; Volmink, Jimmy; Mayosi, Bongani M; Opie, Lionel H

    2017-01-01

    Background Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012. Objectives To assess the effects of beta-blockers on morbidity and mortality endpoints in adults with hypertension. Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015. Selection criteria Randomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults. Data collection and analysis We selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or random-effects meta-analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies

  9. The impact of the 'Better Care Better Value' prescribing policy on the utilisation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for treating hypertension in the UK primary care setting: longitudinal quasi-experimental design.

    Science.gov (United States)

    Baker, Amanj; Chen, Li-Chia; Elliott, Rachel A; Godman, Brian

    2015-09-10

    In April/2009, the UK National Health Service initiated four Better Care Better Value (BCBV) prescribing indicators, one of which encouraged the prescribing of cheaper angiotensin-converting enzyme inhibitors (ACEIs) instead of expensive angiotensin receptor blockers (ARBs), with 80 % ACEIs/20 % ARBs as a proposed, and achievable target. The policy was intended to save costs without affecting patient outcomes. However, little is known about the actual impact of the BCBV indicator on ACEIs/ARBs utilisation and cost-savings. Therefore, this study aimed to evaluate the impact of BCBV policy on ACEIs/ARBs utilisation and cost-savings, including exploration of regional variations of the policy's impact. This cross-sectional study used data from the UK Clinical Practice Research Datalink. Segmented time-series analysis was applied to monthly ACEIs prescription proportion, adjusted number of ACEIs/ARBs prescriptions and costs. Overall, the proportion of ACEIs prescription decreased during the study period from 71.2% in April/2006 to 70.7% in March/2012, with a small but a statistically significant pre-policy reduction in its monthly trend of 0.02% (p < 0.001). Instantly after its initiation, the policy was associated with a sudden reduction in the proportion of ACEIs prescription; however, it resulted in a statistically significant increase in the post-policy monthly trend of ACEIs prescription proportion of 0.013% (p < 0.001), resulting in an overall post-policy slope of -0.007%. Despite this post-policy induced increment, the policy failed to achieve the 80% target, which resulted in missing a potential cost-saving opportunity. The pre-policy trend of the adjusted number of ACEIs/ARBs prescriptions was increasing; however, their trends declined after the policy implementation. The policy affected neither total ACEIs/ARBs cost nor individual ACEIs or ARBs costs. ACEIs/ARBs utilisation was not affected by the BCBV policy. The small increase in post-policy ACEIs

  10. Health outcomes and economic consequences of using angiotensin-converting enzyme inhibitors in comparison with angiotensin receptor blockers in the treatment of arterial hypertension in the contemporary Polish setting.

    Science.gov (United States)

    Wrona, Witold; Budka, Katarzyna; Filipiak, Krzysztof J; Niewada, Maciej; Wojtyniak, Bogdan; Zdrojewski, Tomasz

    2016-01-01

    Arterial hypertension (AH) represents a public health problem in Poland, firstly due to the huge, still growing population of patients (10.45 million patients based on NATPOL 2011 and PolSenior Surveys), and secondly because of the substantial cost of reimbursement from the National Health Fund (NHF). The most commonly used drugs in the treatment of AH include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), the latter being associated with significantly higher unit reimbursement cost. Recent meta-analyses of randomised, controlled trials indicate that there is no medical reason to favour ARBs over ACEIs in AH treatment. To assess the clinical benefit of using ACEIs instead of ARBs and to calculate the potential savings for the payer and patients associated with changing the treatment paradigm to preferential use of ACEIs. The assessment of clinical consequences includes differences between ACEIs and ARBs in terms of average life expectancy and quality-adjusted life years (QALYs) gained. The impact of these drugs on general mortality was estimated based on the meta-analysis carried out by van Vark et al. in 2012. Patients' health-related quality of life was adjusted with Polish population utility norms derived for the EQ-5D-3L questionnaire and additionally for ACEI-induced cough-related utility decrease. Potential savings for the payer on a yearly basis were calculated for a hypothetical cohort of patients who are currently treated with ARBs and might be switched to ACEIs. The number of patients treated with ARBs and ACEIs was estimated based on NHF and IMS Health data. ACEIs were associated with a statistically significant 10% reduction in all-cause mortality, which results in extra life gained of 0.354 years (4.2 months) or an additional 0.201 QALY (2.4 months). Potential annual savings could amount to 112.0 million PLN (25.7 million EUR) and 10.5 million PLN (2.4 million EUR) for the public payer (NHF) and patients

  11. Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular events and residual renal function in dialysis patients: a meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Liu, Youxia; Ma, Xinxin; Zheng, Jie; Jia, Junya; Yan, Tiekun

    2017-06-30

    The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reducing risk of cardiovascular events (CVEs) and preserving kidney function in patients with chronic kidney disease is well-documented. However, the efficacy and safety of these agents in dialysis patients is still a controversial issue. We systematically searched MEDLINE, Embase, Cochrane Library and Wanfang for randomized trials. The relative risk (RR) reductions were calculated with a random-effects model. Major cardiovascular events, changes in GFR and drug-related adverse events were analyzed. Eleven trials included 1856 participants who were receiving dialysis therapy. Compared with placebo or other active agents groups, ARB therapy reduced the risk of heart failure events by 33% (RR 0.67, 95% CI 0.47 to 0.93) with similar decrement in blood pressure in dialysis patients. Indirect comparison suggested that fewer cardiovascular events happened during treatment with ARB (0.77, 0.63 to 0.94). The results indicated no significant differences between the two treatment regimens with regard to frequency of myocardial infarction (1.0, 0.45 to 2.22), stroke (1.16, 0.69 to 1.96), cardiovascular death (0.89, 0.64 to 1.26) and all-cause mortality (0.94, 0.75 to 1.17). Five studies reported the renoprotective effect and revealed that ACEI/ARB therapy significantly slowed the rate of decline in both residual renal function (MD 0.93 mL/min/1.73 m2, 0.38 to 1.47 mL/min/1.73 m2) and urine volume (MD 167 ml, 95% CI 21 ml to 357 ml). No difference in drug-related adverse events was observed in both treatment groups. This study demonstrates that ACE-Is/ARBs therapy decreases the loss of residual renal function, mainly for patients with peritoneal dialysis. Overall, ACE-Is and ARBs do not reduce cardiovascular events in dialysis patients, however, treatment with ARB seems to reduce cardiovascular events including heart failure. ACE-Is and ARBs do not induce an extra risk

  12. 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.

  13. Efficacy of femoral vascular closure devices in patients treated with anticoagulant, abciximab or thrombolytics during percutaneous endovascular procedures

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ha Young; Choo, Sung Wook [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Roh, Hong Gee [Konkuk University School of Medicine, Seoul (Korea, Republic of)] (and others)

    2006-03-15

    This study assessed the outcomes of using vascular closure devices following percutaneous transfemoral endovascular procedures in the patients who were treated with heparin, abciximab thrombolytics (urokinase or t-PA) during the procedures. From March 28, 2003 to August 31, 2004, we conducted a prospective and randomized study in which 1,676 cases of 1.180 patients were treated with one of the two different closure devices (the collagen plug device was Angio-Seal{sup TM.}, the suture-mediated closure device was The Closer S{sup TM}) at the femoral access site after instituting percutaneous endovascular procedures. Among the 1,676 cases, 108 cases (the drug group) were treated with heparin only (n=94), thrombolytics only (n=10), heparin and thrombolytics (n=3), or abciximab and thrombolytics (n=1) during the procedures; 1,568 cases (the no-drug group) were treated without any medication. We compared the efficacy and complications between the two groups. Of the drug group, 42 cases underwent arterial closures with the collagen plug devices and 66 cases underwent arterial closures with the suture-mediated closure devices. We also compared the efficacy and complications between these two group. The immediate hemostasis rates were 92.9% (1,456/1,568) in the no drug group and 91.7% (99/108) in the drug group. Early complications occurred in four cases of the drug group. These included two episodes of rebleeding with using the Closer S, which required manual compression for at least 10 minutes, and two episodes of minor oozing with using one Angio-Seal and one Closer S, which required two hours of additional bed rest. There was no late complication. So, the total success rates were 90.8% (1,423/1,568) in the no-drug group and 88.0% (95/108) in the drug group. These results were not significantly different between the two groups ({rho}=0.34). In the drug group, the difference of the successful hemostasis rate between the collagen plug devices and the suture

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

    Science.gov (United States)

    Evans, David C; Khoo, Kendrick M; Radulescu, Andrei; Cook, Charles H; Gerlach, Anthony T; Papadimos, Thomas J; Steinberg, Steven M; Stawicki, Stanislaw Pa; Eiferman, Daniel S

    2014-10-01

    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. 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. 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. 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.

  15. 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.

  16. Diuretic or Beta-Blocker for Hypertensive Patients Already Receiving ACEI/ARB and Calcium Channel Blocker.

    Science.gov (United States)

    Tsai, Min-Shan; Tang, Chao-Hsiun; Lin, Chia-Ying; Chuang, Po-Ya; Chen, Nai-Chuan; Huang, Chien-Hua; Chang, Wei-Tien; Wang, Tzung-Dau; Yu, Ping-Hsun; Chen, Wen-Jone

    2017-12-01

    In patients already receiving combination of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and calcium channel blocker (CCB), whether the choice of additional diuretic or beta-blocker affects the cardiovascular and cerebrovascular outcomes remains unclear. A total of 13,551 patients who were concurrently receiving three anti-hypertensive agents of different classes through outpatient clinics during 2004-2006 were identified from the National Health Insurance Research Database of Taiwan. Patients were further classified into two treatment groups according to the medication possession ratio of drug combinations; the A + B + C group as those who received concurrent therapy of ACEI/ARB, beta-blocker and CCB. The A + C + D group as patients who received ACEI/ARB, CCB, and diuretics. The event-free survival of stroke, acute myocardial infarction (AMI), mortality, and major adverse cardiovascular events (MACE) between the two treatment groups was investigated. After propensity score matching, there were 5120 patients in each group. There were no differences in the incidence of cardiovascular events between the two groups. In patients with prior history of cerebrovascular accident (CVA), the A + C + D group had a significantly higher AMI-free survival (adjusted HR = 1.56; 95% CI 1.051-2.307; p beta-blocker for treating hypertensive patients with prior CVA history who have already received ACEIs/ARBs and CCBs.

  17. Comparison of abciximab versus eptifibatide during percutaneous coronary intervention in ST-segment elevation myocardial infarction (from the HORIZONS-AMI trial).

    Science.gov (United States)

    Singh, Harsimran S; Dangas, George D; Guagliumi, Giulio; Yu, Jennifer; Witzenbichler, Bernhard; Kornowski, Ran; Grines, Cindy; Gersh, Bernard; Dudek, Darius; Mehran, Roxana; Stone, Gregg W

    2012-10-01

    There are limited safety and effectiveness data comparing glycoprotein IIb/IIIa inhibitors in the setting of primary percutaneous coronary intervention. In this substudy of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, the clinical and bleeding outcomes of eptifibatide versus abciximab were evaluated in patients with ST-segment elevation myocardial infarction who underwent percutaneous coronary intervention. Three-year clinical outcomes of patients in the heparin plus glycoprotein IIb/IIIa inhibitor arm were compared according to treatment with abciximab (n = 907) versus eptifibatide (n = 803). Adjudicated end points included major adverse cardiovascular events (MACEs; mortality, reinfarction, ischemia-driven target vessel revascularization, or stroke), major bleeding, and net adverse clinical events (MACEs or major bleeding). Propensity score matching was used to identify 1,342 matched cases (671 each in the abciximab and eptifibatide groups). Multivariate analysis was performed in the entire cohort and the propensity-matched groups. At 3-year follow-up, eptifibatide and abciximab resulted in nonsignificantly different rates of MACEs (18.3% vs 19.6%, hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.74 to 1.16, p = 0.51), major bleeding (10.7% vs 11.9%, HR 0.90, 95% CI 0.67 to 1.19, p = 0.44), and net adverse clinical events (24.5% vs 25.5%, HR 0.96, 95% CI 0.79 to 1.17, p = 0.69). Similarly, at 3 years by multivariate analysis, there was no statistically significant difference between abciximab and eptifibatide for net adverse clinical events (HR 0.89, 95% CI 0.73 to 1.09, p = 0.27), MACEs (HR 0.96, 95% CI 0.77 to 1.20, p = 0.73), and major bleeding (HR 1.05, 95% CI 0.78 to 1.41, p = 0.75). The propensity-matched groups also had similar outcomes. In conclusion, abciximab and eptifibatide have comparable bleeding risks and clinical efficacy in primary percutaneous coronary intervention

  18. Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Huang Jianhua

    2008-12-01

    Full Text Available Abstract Background The use of abciximab (c7E3 Fab or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These β3 integrin inhibitors antagonize fibrinogen binding to αIIbβ3 integrins on platelets and ligand binding to αvβ3 integrins on vascular cells. αvβ3 integrins influence responses to insulin in various cell types but effects in human aortic smooth muscle cells (HASMC are unknown. Results and discussion Insulin elicited a dose-dependent proliferative response in HASMC. Pretreatment with m7E3 (an anti-β3 integrin monoclonal antibody from which abciximab is derived, c7E3 or LM609 inhibited proliferative responses to insulin by 81%, 59% and 28%, respectively. Eptifibatide or cyclic RGD peptides completely abolished insulin-induced proliferation whereas tirofiban, which binds αIIbβ3 but not αvβ3, had no effect. Insulin-induced increases in c-Jun NH2-terminal kinase-1 (JNK1 activity were partially inhibited by m7E3 and eptifibatide whereas antagonism of αvβ3 integrins had no effect on insulin-induced increases in extracellular signal-regulated kinase (ERK activity. Insulin stimulated a rapid increase in the number of vinculin-containing focal adhesions per cell and treatment with m7E3, c7E3 or eptifibatide inhibited insulin-induced increases in focal adhesions by 100%, 74% and 73%, respectively. Conclusion These results demonstrate that αvβ3 antagonists inhibit signaling, focal adhesion formation and proliferation of insulin-treated HASMC.

  19. Eptifibatide and abciximab inhibit insulin-induced focal adhesion formation and proliferative responses in human aortic smooth muscle cells

    Science.gov (United States)

    Pathak, Alokkumar; Zhao, Renyi; Huang, Jianhua; Stouffer, George A

    2008-01-01

    Background The use of abciximab (c7E3 Fab) or eptifibatide improves clinical outcomes in diabetics undergoing percutaneous coronary intervention. These β3 integrin inhibitors antagonize fibrinogen binding to αIIbβ3 integrins on platelets and ligand binding to αvβ3 integrins on vascular cells. αvβ3 integrins influence responses to insulin in various cell types but effects in human aortic smooth muscle cells (HASMC) are unknown. Results and discussion Insulin elicited a dose-dependent proliferative response in HASMC. Pretreatment with m7E3 (an anti-β3 integrin monoclonal antibody from which abciximab is derived), c7E3 or LM609 inhibited proliferative responses to insulin by 81%, 59% and 28%, respectively. Eptifibatide or cyclic RGD peptides completely abolished insulin-induced proliferation whereas tirofiban, which binds αIIbβ3 but not αvβ3, had no effect. Insulin-induced increases in c-Jun NH2-terminal kinase-1 (JNK1) activity were partially inhibited by m7E3 and eptifibatide whereas antagonism of αvβ3 integrins had no effect on insulin-induced increases in extracellular signal-regulated kinase (ERK) activity. Insulin stimulated a rapid increase in the number of vinculin-containing focal adhesions per cell and treatment with m7E3, c7E3 or eptifibatide inhibited insulin-induced increases in focal adhesions by 100%, 74% and 73%, respectively. Conclusion These results demonstrate that αvβ3 antagonists inhibit signaling, focal adhesion formation and proliferation of insulin-treated HASMC. PMID:19108709

  20. 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 ...

  1. Relationship between early administration of abciximab and TIMI flow in STEMI patients undergoing primary angioplasty: findings from a large regional STEMI network.

    Science.gov (United States)

    Izzo, Antonio; Rosiello, Renato; Lucchini, Giuseppe; Tomasi, Luca; Mantovani, Paola; Lettieri, Corrado; Baccaglioni, Nicola; Romano, Michele; Buffoli, Francesca; Izzo, Beatrice; Zanini, Roberto

    2017-06-01

    The aim of this study is to assess whether in S-T Elevation Myocardial Infarction (STEMI) a relationship between early administration of abciximab and Thrombolysis In Myocardial Infarction (TIMI) flow before and after primary percutaneous coronary intervention (PCI) in 960 consecutive patients exists. From 1 February 2001 onward, in the Province of Mantua it has been operating a 'Cardiology Network for the Acute Infarction Care' having its Hub in the Central Coronary ICU/Cath Lab of Mantua Hospital and being its Spokes centers represented by the emergency rooms and Central Coronary ICUs of the four territorial hospitals. T1 (time from symptoms onset to first medical contact) and T2 (time from first medical contact to angioplasty) are shorter for patients rescued by first aid units rather than for those presented in emergency rooms as well as Ta (time from symptoms onset to abciximab administration). Furthermore, the patients that received abciximab before hospital arrival had less frequently a coronary occlusion [odds ratio = 0.74, 95% confidence interval (0.57-0.96), P = 0.013]. The patients with T1 less than 4 h are 753/960 (78.4%). For this type of patients, there was a significant Ta difference between the pre-PCI TIMI-flow classes (F = 4.467, df = 3, P = 0.04). Planned contrasts revealed that mean time of TIMI flow 0 (M = 104.2) is statistically different from mean time of TIMI flow 3 (M = 85.7), P = 0.013. Our results suggest that the use of abciximab, free from pharmacokinetic limits of oral P2Y12 inhibitors, should be considered in STEMI patients with early presentation before primary PCI.

  2. Influence of abciximab on the adhesion of platelets on a shielded plasma gradient prepared on polyethylene

    NARCIS (Netherlands)

    Spijker, HT; Busscher, HJ; van Oeveren, W

    2002-01-01

    Introduction: Thrombotic effects of biomaterial implants are mediated merely through activation of the platelet glycoprotein IIb-Illa (GpIIb-IIIa) receptor. Consequently, platelet GpIIb-IIIa receptor inhibitors are successfully used during stent implantation procedures to prevent thrombosis.

  3. Early recovery of microvascular perfusion induced by t-PA in combination with abciximab or eptifibatide during postischemic reperfusion

    Directory of Open Access Journals (Sweden)

    Giusti Andrea

    2002-06-01

    Full Text Available Abstract Background GPIIb/IIIa inhibitors abciximab and eptifibatide have been shown to inhibit platelet aggregation in ischemic heart disease. Our aim was to test the efficacy of abiciximab (Reo Pro or eptifibatide (Integrilin alone or in combination with plasminogen activator (t-PA in an experimental model of ischemia reperfusion (I/R in hamster cheek pouch microcirculation visualized by fluorescence microscopy. Hamsters were treated with saline, or abiciximab or eptifibatide or these drugs combined with t-PA infused intravenously 10 minutes before ischemia and through reperfusion. We measured the microvessel diameter changes, the arteriolar red blood cell (RBC velocity, the increase in permeability, the perfused capillary length (PCL, and the platelet and leukocyte adhesion on microvessels. Results I/R elicited large increases in the platelet and leukocyte adhesion and a decrease in microvascular perfusion. These responses were significantly attenuated by abiciximab or eptifibatide (PCL:70 and 65% at 5–10 mins of reperfusion and 85 and 87% at 30 mins of reperfusion, respectively, p Conclusions Platelets are crucial in I/R injury, as shown by the treatment with abicixmab or eptifibatide, which decreased platelet aggregation in microvessels, and also decreased leukocyte adhesion in venules. Arterial vasoconstriction, decreased arterial RBC velocity and alterations in the endothelial barrier with increased permeability delayed the complete restoration of blood flow, while t-PA combined with inhibition of platelet aggregation speeded up the capillary perfusion after reperfusion.

  4. Early recovery of microvascular perfusion induced by t-PA in combination with abciximab or eptifibatide during postischemic reperfusion

    Science.gov (United States)

    Bertuglia, Silva; Giusti, Andrea

    2002-01-01

    Background GPIIb/IIIa inhibitors abciximab and eptifibatide have been shown to inhibit platelet aggregation in ischemic heart disease. Our aim was to test the efficacy of abiciximab (Reo Pro) or eptifibatide (Integrilin) alone or in combination with plasminogen activator (t-PA) in an experimental model of ischemia reperfusion (I/R) in hamster cheek pouch microcirculation visualized by fluorescence microscopy. Hamsters were treated with saline, or abiciximab or eptifibatide or these drugs combined with t-PA infused intravenously 10 minutes before ischemia and through reperfusion. We measured the microvessel diameter changes, the arteriolar red blood cell (RBC) velocity, the increase in permeability, the perfused capillary length (PCL), and the platelet and leukocyte adhesion on microvessels. Results I/R elicited large increases in the platelet and leukocyte adhesion and a decrease in microvascular perfusion. These responses were significantly attenuated by abiciximab or eptifibatide (PCL:70 and 65% at 5–10 mins of reperfusion and 85 and 87% at 30 mins of reperfusion, respectively, p eptifibatide, was more effective and microvascular perfusion recovered immediately after postischemic reperfusion. Conclusions Platelets are crucial in I/R injury, as shown by the treatment with abicixmab or eptifibatide, which decreased platelet aggregation in microvessels, and also decreased leukocyte adhesion in venules. Arterial vasoconstriction, decreased arterial RBC velocity and alterations in the endothelial barrier with increased permeability delayed the complete restoration of blood flow, while t-PA combined with inhibition of platelet aggregation speeded up the capillary perfusion after reperfusion. PMID:12086588

  5. Eptifibatide is associated with significant cost savings and similar clinical outcomes to abciximab when used during primary percutaneous coronary intervention for ST-elevation myocardial infarction: An observational cohort study of 3863 patients.

    Science.gov (United States)

    Rathod, K S; Antoniou, S; Avari, P; Ding, N; Wright, P; Knight, C; Jain, A K; Mathur, A; Smith, E J; Weerackody, R; Wragg, A; Jones, D A

    2017-01-01

    Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. There are few studies directly comparing these agents. The aim of this study was to assess whether eptifibatide is a safe and cost-effective alternative to abciximab in the treatment of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. This was an observational cohort study of 3863 patients who received a GPIIb/IIIa inhibitor whilst undergoing primary percutaneous coronary intervention from 2007 to 2014. Patients who did not receive a GPIIb/IIIa inhibitor were excluded. Time to first major adverse cardiac event defined as death, non-fatal myocardial infarction, stroke or target vessel revascularization, and total hospital costs were compared between the groups. In all, 1741 patients received abciximab with 2122 receiving eptifibatide. Patients who received eptifibatide had higher rates of previous MI/percutaneous coronary intervention and were more likely to undergo a procedure from the radial route. Unadjusted Kaplan-Meier analysis revealed no significant difference in the 1-year event rates between patients given eptifibatide versus abciximab (p = 0.201). Age-adjusted Cox analysis demonstrated no difference in 1-year outcome between abciximab and eptifibatide (hazard ratio: 0.83; 95% confidence interval: 0.73-1.39), which persisted after multivariate adjustment (hazard ratio: 0.92; 95% confidence interval: 0.79-1.56) including the incorporation of a propensity score (hazard ratio: 0.88; 95% confidence interval: 0.71-1.44). Eptifbatide was associated with significant cost savings being 87% cheaper overall compared to abciximab (on average £650 cheaper per patient and saving approximately £950,000). This observational data suggest that eptifibatide is associated with similar outcomes and significant cost savings compared to abciximab when

  6. Effects of TRA-418, a novel TP-receptor antagonist, and IP-receptor agonist, on human platelet activation and aggregation.

    Science.gov (United States)

    Miyamoto, Mitsuko; Yamada, Naohiro; Ikezawa, Shiho; Ohno, Michihiro; Otake, Atsushi; Umemura, Kazuo; Matsushita, Teruo

    2003-11-01

    [4-[2-(1,1-Diphenylethylsulfanyl)-ethyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-yloxy]-acetic acid N-Methyl-d-glucamine salt (TRA-418) has both thromboxane A2 (TP)-receptor antagonist and prostacyclin (IP)-receptor agonist properties. The present study examined the advantageous effects of TRA-418 based on the dual activities, over an agent having either activity alone and also the difference in the effects of TRA-418 and a glycoprotein alphaIIb/beta3 integrin (GPIIb/IIIa) inhibitor. TRA-418 inhibited platelet GPIIb/IIIa activation as well as P-selectin expression induced by adenosine 5'-diphosphate, thrombin receptor agonist peptide 1-6 (Ser-Phe-Leu-Leu-Arg-Asn-NH2), and U-46619 in the presence of epinephrine (U-46619+ epinephrine). TRA-418 also inhibited platelet aggregation induced by those platelet-stimulants in Ca2+ chelating anticoagulant, citrate and in nonchelating anticoagulant, d-phenylalanyl-l-prolyl-l-arginyl-chloromethyl ketone (PPACK). The TP-receptor antagonist SQ-29548 inhibited only U-46619+epinephrine-induced GPIIb/IIIa activation, P-selectin expression, and platelet aggregation. The IP-receptor agonist beraprost sodium inhibited platelet activation. Beraprost also inhibited platelet aggregation induced by platelet stimulants we tested in citrate and in PPACK. The GPIIb/IIIa inhibitor abciximab blocked GPIIb/IIIa activation and platelet aggregation. However, abciximab showed slight inhibitory effects on P-selectin expression. TRA-418 is more advantageous as an antiplatelet agent than TP-receptor antagonists or IP-receptor agonists separately used. TRA-418 showed a different inhibitory profile from abciximab in the effects on P-selectin expression.

  7. Intracoronary Compared to Intravenous Abciximab in Patients with ST Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention Reduces Mortality, Target Vessel Revascularization and Reinfarction after 1 Year

    DEFF Research Database (Denmark)

    Iversen, Allan Zeeberg; Galatius, Soeren; Abildgaard, Ulrik

    2011-01-01

    Objectives: Administration of the glycoprotein IIb/IIIa inhibitor abciximab to patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) improves outcome. Data have suggested that an intracoronary (IC) bolus might be superior...... to the standard intravenous (IV) administration. We have previously reported reduced short-term mortality and need for target vessel revascularization (TVR) with the IC route. We now present long-term data from our randomized trial on IC versus IV abciximab in pPCI-treated STEMI patients. Methods: A total of 355...

  8. A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease.

    Science.gov (United States)

    Han, Sang-Oh; Pope, Rand; Li, Songtao; Kishnani, Priya S; Steet, Richard; Koeberl, Dwight D

    2016-02-01

    Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) fails to completely reverse muscle weakness in Pompe disease. β2-agonists enhanced ERT by increasing receptor-mediated uptake of rhGAA in skeletal muscles. To test the hypothesis that a β-blocker might reduce the efficacy of ERT, because the action of β-blockers opposes those of β2-agonists. Mice with Pompe disease were treated with propranolol (a β-blocker) or clenbuterol in combination with ERT, or with ERT alone. Propranolol-treated mice had decreased weight gain (pblocker, reduced weight, increased left ventricular mass and decreased glycogen clearance in skeletal muscle following ERT. β-Blockers might therefore decrease the efficacy from ERT in patients with Pompe disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Current role of beta-blockers in the treatment of hypertension.

    Science.gov (United States)

    Aronow, Wilbert S

    2010-11-01

    It is important to know which patients with hypertension will benefit from beta-blocker therapy and which beta-blockers should be used in the treatment of hypertension to reduce cardiovascular events and mortality. Studies between 1981 and 2009 using a Medline search are reported. Beta-blockers should be used to treat hypertension in patients with previous myocardial infarction, acute coronary syndromes, angina pectoris, congestive heart failure, ventricular arrhythmias, supraventricular tachyarrhythmias, diabetes mellitus, after coronary artery bypass graft surgery, and in patients who are pregnant, have thyrotoxicosis, glaucoma, migraine, essential tremor, perioperative hypertension, or an excessive blood pressure response after exercise. The use of beta-blockers as first-line therapy in patients with primary hypertension has been controversial. However, the 2009 guidelines of the European Society of Hypertension state that large-scale meta-analyses of available data confirm that diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers do not significantly differ in their ability to lower blood pressure and to exert cardiovascular protection both in elderly and in younger patients. The key message of this paper is that atenolol should not be used as an antihypertensive drug and that the degree of reduction of mortality, myocardial infarction, stroke and congestive heart failure by antihypertensive therapy is dependent on the degree of lowering of aortic blood pressure. Newer vasodilator beta-blockers such as carvedilol and nebivolol may be more effective in reducing cardiovascular events than traditional beta-blockers, but this needs to be investigated by controlled clinical trials.

  10. 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.

  11. Topical beta-blockers and mortality

    NARCIS (Netherlands)

    Müskens, Rogier P. H. M.; Wolfs, Roger C. W.; Witteman, Jacqueline C. M.; Hofman, Albert; de Jong, Paulus T. V. M.; Stricker, Bruno H. C.; Jansonius, Nomdo M.

    2008-01-01

    To study the associations between long-term and short-term use of topical beta-blockers and mortality. Prospective population-based cohort study. To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484 incident beta-blocker users and

  12. 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

  13. Intracoronary Compared to Intravenous Abciximab in Patients with ST Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention Reduces Mortality, Target Vessel Revascularization and Reinfarction after 1 Year

    DEFF Research Database (Denmark)

    Iversen, Allan Zeeberg; Galatius, Soeren; Abildgaard, Ulrik

    2011-01-01

    to the standard intravenous (IV) administration. We have previously reported reduced short-term mortality and need for target vessel revascularization (TVR) with the IC route. We now present long-term data from our randomized trial on IC versus IV abciximab in pPCI-treated STEMI patients. Methods: A total of 355...

  14. The development of new-onset type 2 diabetes associated with choosing a calcium channel blocker compared to a diuretic or beta-blocker.

    Science.gov (United States)

    Kuti, Effie L; Baker, William L; White, C Michael

    2007-06-01

    It has been acknowledged that patients who receive a beta-blocker or diuretic based regimen are at increased risk of developing new-onset diabetes. Recently, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to decrease patients' odds of developing new-onset type 2 diabetes. A number of large placebo-controlled multi-center trials in post-myocardial infarction and heart failure patients have shown the ability of renin-angiotensin-aldosterone system medications to reduce the onset of type 2 diabetes. Pharmacologic data has shown improved insulin sensitivity with ACEIs and ARBs. Controversy persists regarding the influence of calcium channel blockers on the development of new-onset diabetes. Two reviewers conducted a systematic literature search of Medline, EMBASE, CINAHL, and the Cochrane Library (1966 to December 2006) to extract a consensus of trial data involving calcium channel blockers versus diuretics or beta-blockers with an endpoint of new-onset type 2 diabetes. Studies were included if they were randomized controlled trials versus routine treatment, not observational studies of clinical practice. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. Out of 1721 trials, six meeting inclusion criteria were identified, including 99 006 patients. Calcium channel blockers were associated with a reduced incidence of new-onset type 2 diabetes (odds ratio 0.81; 95% confidence interval [CI] 0.73-0.90; p = 0.0001) compared with diuretic or beta-blocker therapy. The reduction in new-onset type 2 diabetes was maintained when a calcium channel blocker was compared to only thiazide diuretics (OR 0.86; 95% CI 0.75-0.99; p = 0.0346). The meta-analysis was limited by the varying definition of new-onset type 2 diabetes mellitus, as well as the potential for publication bias, which is a limit of any meta-analysis. Calcium channel blockers may be associated with reduced odds of developing

  15. 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

  16. 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

  17. P2Y12 Receptor Blockade Augments Glycoprotein IIb‐IIIa Antagonist Inhibition of Platelet Activation, Aggregation, and Procoagulant Activity

    Science.gov (United States)

    Berny‐Lang, Michelle A.; Jakubowski, Joseph A.; Sugidachi, Atsuhiro; Barnard, Marc R.; Michelson, Alan D.; Frelinger, Andrew L.

    2013-01-01

    Background New antiplatelet agents that provide greater, more consistent inhibition of the platelet ADP receptor P2Y12 may be used in combination with glycoprotein (GP) IIb‐IIIa antagonists, but their combined effect on platelet function and procoagulant activity is not well studied. Therefore, the objective of this study was to evaluate the independent and complementary effects of P2Y12 and GPIIb‐IIIa inhibition on platelet function and procoagulant activity. Methods and Results Healthy donor blood was treated with the active metabolite of prasugrel (R‐138727 5 μmol/L), GPIIb‐IIIa antagonists (abciximab 3 μg/mL or eptifibatide 0.9 μg/mL), and combinations thereof, exposed to physiologically relevant agonists (collagen and ADP) and then evaluated for markers of platelet activation and procoagulant activity. Significant interactions between R‐138727 and GPIIb‐IIIa antagonists were observed. R‐138727 and the GPIIb‐IIIa antagonists had additive inhibitory effects on collagen‐stimulated platelet aggregation and on the collagen plus ADP–stimulated level of activated platelet surface GPIIb‐IIIa. R‐138727 and abciximab each inhibited collagen plus ADP–stimulated platelet phosphatidylserine expression and prothrombin cleavage, and the combination produced greater inhibition than achieved with abciximab alone. In contrast, eptifibatide did not inhibit, but instead enhanced, collagen plus ADP–stimulated prothrombin cleavage. Addition of R‐138727 reduced prothrombin cleavage in eptifibatide‐treated samples, suggesting a novel mechanism for potential benefit from combined prasugrel and eptifibatide treatment. Conclusions The complementary effects of abciximab and R‐138727 on platelet activation, aggregation, and procoagulant activity suggest their combined use may, to a greater degree than with either agent alone, reduce thrombus formation in vivo. PMID:23676293

  18. 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.

  19. Eptifibatide is associated with significant cost savings and similar clinical outcomes to abciximab when used during primary percutaneous coronary intervention for ST-elevation myocardial infarction: An observational cohort study of 3863 patients

    Directory of Open Access Journals (Sweden)

    KS Rathod

    2017-10-01

    Full Text Available Introduction Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. There are few studies directly comparing these agents. The aim of this study was to assess whether eptifibatide is a safe and cost-effective alternative to abciximab in the treatment of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Methods This was an observational cohort study of 3863 patients who received a GPIIb/IIIa inhibitor whilst undergoing primary percutaneous coronary intervention from 2007 to 2014. Patients who did not receive a GPIIb/IIIa inhibitor were excluded. Time to first major adverse cardiac event defined as death, non-fatal myocardial infarction, stroke or target vessel revascularization, and total hospital costs were compared between the groups. Results In all, 1741 patients received abciximab with 2122 receiving eptifibatide. Patients who received eptifibatide had higher rates of previous MI/percutaneous coronary intervention and were more likely to undergo a procedure from the radial route. Unadjusted Kaplan–Meier analysis revealed no significant difference in the 1-year event rates between patients given eptifibatide versus abciximab (p = 0.201. Age-adjusted Cox analysis demonstrated no difference in 1-year outcome between abciximab and eptifibatide (hazard ratio: 0.83; 95% confidence interval: 0.73–1.39, which persisted after multivariate adjustment (hazard ratio: 0.92; 95% confidence interval: 0.79–1.56 including the incorporation of a propensity score (hazard ratio: 0.88; 95% confidence interval: 0.71–1.44. Eptifbatide was associated with significant cost savings being 87% cheaper overall compared to abciximab (on average £650 cheaper per patient and saving approximately £950,000. Conclusion This observational data suggest that eptifibatide is associated with similar

  20. [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.

  1. Effect of a Dual Drug-Coated Stent With Abciximab and Alpha-Lipoic Acid in a Porcine Coronary Restenosis Model

    Science.gov (United States)

    Lim, Kyung Seob; Hong, Young Joon; Hachinohe, Daisuke; Ahmed, Khurshid; Kim, Jung Ha; Sim, Doo Sun; Lee, Min Goo; Park, Keun-Ho; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Song, Sun-Jung; Jung, Kyoung Woon; Cho, Dong Lyun; Kang, Jung Chaee

    2011-01-01

    Background and Objectives The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of a stent coated with abciximab and alpha-lipoic acid (ALA) in a porcine coronary overstretch restenosis model. Materials and Methods A total of 10 pigs were randomized into two groups (10 pigs, 10 coronaries in each group) in which the coronary arteries were stented with a dual-coated stent and a bare metal stent (control) by randomization. Stents were deployed with oversizing (stent/artery ratio 1.3 : 1) in the porcine coronary arteries, and histopathology was assessed 28 days after stenting. Results There was no significant difference in the injury score between the two groups. In the neointima, the lymphohistiocyte count was significantly lower in dual-coat stent group compared with the control stent group (120±85 cells vs. 159±80 cells, p=0.048). There was no significant difference in the fibrin score between the two groups (0.16±0.34 in the dual-coated stent group vs. 0.25±0.48 in the control stent group, p=0.446). The neointima area was not significantly different between both groups (1.55±0.8 mm2 in dual-coated stent group vs. 1.40±0.86 mm2 in the control stent group, p=0.447). Conclusion Although the dual-coated stent with abciximab and ALA showed no significant difference in inhibition of neointimal hyperplasia when compared with the bare metal stent, it was associated with a reduced inflammatory reaction when compared with the control stent in a porcine coronary restenosis model. PMID:21731564

  2. A novel antihypertension agent, sargachromenol D from marine brown algae, Sargassum siliquastrum, exerts dual action as an L-type Ca2+channel blocker and endothelin A/B2receptor antagonist.

    Science.gov (United States)

    Park, Byong-Gon; Shin, Woon-Seob; Oh, Sangtae; Park, Gab-Man; Kim, Nam Ik; Lee, Seokjoon

    2017-09-01

    We isolated the novel vasoactive marine natural products, (5E,10E)-14-hydroxy-2,6,10-trimethylpentadeca-5,10-dien-4-one (4) and sargachromenol D (5), from Sargassum siliquastrum collected from the coast of the East Sea in South Korea by using activity-guided HPLC purification. The compounds effectively dilated depolarization (50mMK + )-induced basilar artery contraction with EC 50 values of 3.52±0.42 and 1.62±0.63μM, respectively, but only sargachromenol D (5) showed a vasodilatory effect on endothelin-1 (ET-1)-induced basilar artery contraction (EC 50 =9.8±0.6μM). These results indicated that sargachromenol D (5) could act as a dual antagonist of l-type Ca 2+ channel and endothelin A/B 2 receptors. Moreover, sargachromenol D (5) lowered blood pressure in spontaneous hypertensive rats (SHRs) 2h after oral treatment at a dose of 80mg/kg dose and the effect was maintained for 24h. Based on our ex vivo and in vivo experiments, we propose that sargachromenol D (5) is a strong candidate for the treatment of hypertension that is not controlled by conventional drugs, in particular, severe-, type II diabetes-, salt-sensitive, and metabolic disease-induced hypertension. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. 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

    2017-09-02

    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.

  4. Pulmonary safety of ophthalmic beta-blockers

    DEFF Research Database (Denmark)

    Kristensen, Mathias L.; Simonsen, Jan Henrik; Torp-Pedersen, Christian

    2018-01-01

    PURPOSE: Ophthalmic beta-blockers, used in the treatment of increased intraocular pressure, are known to cause pulmonary adverse effects. Few, if any, studies have quantified the extent of the problem in a real-life population. In this nationwide study, we assess the pulmonary safety of patients...... initiating treatment with ophthalmic beta-blockers. METHODS: Using the Danish Nationwide Registries from 1995 to 2012, we identified all individuals aged 20-90 years who initiated monotherapy with an intraocular pressure-lowering drug, with or without concomitant obstructive pulmonary disease. Risks of (i...... concomitant obstructive pulmonary disease (n = 86 568) were as follows: 1.47 for beta-blockers (95% confidence interval (CI): 1.35-1.61; p

  5. Drug: D02778 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02778 Drug Abciximab (genetical recombination) (JAN); Abciximab (USAN/INN); Reopro...IC AGENTS B01A ANTITHROMBOTIC AGENTS B01AC Platelet aggregation inhibitors excl. heparin B01AC13 Abciximab D02778 Abciximab (genetica...PIIb/IIIa) receptor [HSA:3674 3690] [KO:K06476 K06493] Abciximab [ATC:B01AC13] D02778 Abciximab (genetical r

  6. Topical beta-Blockers and Mortality

    NARCIS (Netherlands)

    Muskens, Rogier P. H. M.; Wolfs, Roger C. W.; Wittenian, Jacqueline C. M.; Hofman, Albert; de Jong, Paulus T. V. M.; Stricker, Bruno H. C.; Jansonius, Nomdo M.

    2008-01-01

    Purpose: To study the associations between long-term and short-term use of topical beta-blockers and mortality. Design: Prospective population-based cohort study. Participants: To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484

  7. Are we misunderstanding beta-blockers.

    Science.gov (United States)

    Cruickshank, J M

    2007-08-09

    In myocardial ischaemia and heart failure, beta-blockers with intrinsic sympathomimetic activity (ISA) e.g. pindolol, xamoterol, bucindolol, nebivolol, have performed poorly in reducing morbidity and mortality. In both indications beta-1 blockade is the vital active ingredient. Beta-1 blockade (bisoprolol) is now an alternative first-line choice to Ace-inhibition in the treatment of heart failure. The therapeutic role of beta-blockers in hypertension is less well understood, particularly since the new recommendations in the UK from the NICE committee stating that: 1. beta-blockers are no longer preferred as a routine initial therapy, 2. the combination with diuretics is discouraged due to the risk of induced diabetes, and 3. in younger patients first-choice initial therapy should be an ACE-inhibitor. Recent data from the Framingham Heart Study and other epidemiological studies have indicated that the development of diastolic hypertension in younger subjects is closely linked to weight-increase and an increase in peripheral resistance; such subjects have a high adrenergic drive and cardiac output. In contrast, elderly systolic hypertension mostly arises de novo via poor vascular compliance. Thus in younger, probably overweight, hypertensives (including diabetics) first-line beta-blockade has performed well in preventing myocardial infarction (a fact hidden by meta-analyses that do not take age into account). Conversely, in elderly hypertensives first-line beta-blockade (atenolol) has performed poorly in reducing cardiovascular risk (due to partial beta-2 blockade atenolol evokes metabolic disturbance and does not improve vascular compliance, or effectively lower central aortic pressure or reverse left ventricular hypertrophy). Thus beta-blockers like atenolol are ill-equipped for first-line therapy in elderly hypertension. Some beta-blockers, e.g. bisoprolol (up to 10 mg/day is highly beta-1 selective) and nebivolol (beta-2/3 intrinsic sympathomimetic activity), do

  8. Lowering blood pressure with beta-blockers in combination with other renin-angiotensin system blockers in patients with hypertension and type 2 diabetes: results from the GEMINI Trial.

    Science.gov (United States)

    Wright, Jackson T; Bakris, George L; Bell, David S H; Fonseca, Vivian; Katholi, Richard E; McGill, Janet B; Messerli, Franz H; Phillips, Robert A; Raskin, Philip; Holdbrook, Fred K; Lukas, Mary Ann; Iyengar, Malini

    2007-11-01

    The effects of beta-blockade in addition to more specific renin-angiotensin system (RAS) blockers on blood pressure (BP) in patients with diabetes are described. After washout of medications other than angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, patients were titrated to a BP level <130/80 mm Hg using therapy with carvedilol 6.25 to 25 mg bid (n=498) or metoprolol tartrate 50 to 200 mg bid (n=737). At the end of the beta-blocker titration period, a BP level <130/80 mm Hg was achieved in 37% of carvedilol-treated and 36% of metoprolol-treated participants who continued to receive a renin-angiotensin system blocker. In the approximately 60% of participants in whom a BP level <130/80 mm Hg was not attained with renin-angiotensin system blockade plus beta-blockade, hydrochlorothiazide was added in 43% and 44% of carvedilol and metoprolol groups, respectively; 25% (both arms) also required a calcium channel blocker. Among those in whom goal BP was not achieved, 42% of carvedilol- and 40% of metoprolol-treated participants were not titrated to the highest dose of beta-blocker. The use of carvedilol compared with metoprolol did not effect glycemic control.

  9. Beta-Blocker Drug Use and Survival among Patients with Pancreatic Adenocarcinoma.

    Science.gov (United States)

    Udumyan, Ruzan; Montgomery, Scott; Fang, Fang; Almroth, Henrik; Valdimarsdottir, Unnur; Ekbom, Anders; Smedby, Karin E; Fall, Katja

    2017-07-01

    Preclinical studies have suggested that β-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adenocarcinoma (PDAC). All patients diagnosed with a first primary PDAC in Sweden between 2006 and 2009 were identified through the Swedish Cancer Register (n = 2,394). We obtained information about use of beta-blockers and other medications through linkage with the national Prescribed Drug Register. Cancer-specific mortality was assessed using the Swedish Cause of Death Register. We used multivariable Cox regression adjusted for sociodemographic factors, tumor characteristics, comorbidity score, and other medications to estimate HRs and 95% confidence intervals (CI) for cancer-specific mortality associated with beta-blocker use during the 90-day period before cancer diagnosis. A total of 2,054 (86%) died, with pancreatic cancer recorded as the underlying cause of death during a maximum of 5-year follow-up (median 5 months). Patients who used beta-blockers (n = 522) had a lower cancer-specific mortality rate than nonusers (adjusted HR, 0.79; 95% CI, 0.70-0.90; P beta-blocker receptor selectivity. Our results support the concept that beta-blocker drugs may improve the survival of PDAC patients, particularly among those with localized disease. Cancer Res; 77(13); 3700-7. ©2017 AACR. ©2017 American Association for Cancer Research.

  10. [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.

  11. [True and presumed contraindications of beta blockers. Peripheral vascular disease, diabetes mellitus, chronic bronchopneumopathy].

    Science.gov (United States)

    Pozzi, R

    2000-08-01

    Traditional contraindications to beta-blockers are peripheral vascular diseases, diabetes mellitus, chronic obstructive pulmonary disease (COPD) and asthma. Recent data seem to show that rigorous application of these rules are not completely justified and indicate that many patients would be inappropriately excluded from the beneficial effects of this therapy. Appraisal of clear guidelines for a safe use of beta-blockers is thus mandatory for the clinician. A brief review of the effects of beta-adrenergic receptor blockade is offered. The therapy is aimed at blocking beta 1-receptors. On the other hand, the block of beta 2-receptors causes the well known side effects, i.e. vasoconstriction, delayed response to hypoglycemia in diabetic patients, bronchoconstriction. From the first compound, propranolol, with uniform action on beta 1 and beta 2-receptors, further generation of beta-blockers were subsequently developed: beta 1-selective, with intrinsic sympathomimetic activity, and with associated vasodilating "ancillary" property. Some favorable reduction in collateral effects has thus been obtained with new compounds, without reaching complete safety. Examination of exclusion criteria applied in clinical trials offers no useful indications because of their imprecise definition. Examination of the literature and a more accurate understanding of the diseases, traditionally considered contraindications, may help setting up a uniform and clear path: peripheral vascular disease: beta-blockers should be avoided only in those patients with vasospastic disorders, rest pain with severe peripheral vascular disease or nonhealing lesions. In patients with mild to moderate disease, beta-blockers can be prescribed, but careful surveillance for any changes in symptoms related to intermittent claudicatio should be achieved; diabetes mellitus: previous apprehension for the lessening reaction to hypoglycemia in patients treated with insulin has been retracted. Beta-blockers are not

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

    African Journals Online (AJOL)

    type of calcium-channel blocker, e.g. amlodipine, but not with a nondihydropyridine type, e.g. verapamil. However, there is very little evidence of efficacy in this regard. What is the role of beta blockers? Beta blockers should not be prescribed as monotherapy for hypertension. They can be added to other drugs for blood.

  13. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  14. 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...

  15. Adrenergic beta-receptor blockers in hypertension of pregnancy.

    Science.gov (United States)

    Sandström, B

    1982-01-01

    This is a study of the selective beta-blocking agent metoprolol in combination with either thiazide or hydralazine in 184 hypertensive gravidae. The effects on the mother and the fetus are compared with those of 97 hypertensive gravidae treated with a combination of hydralazine and a thiazide. The combination of metoprolol and hydralazine seems to be the most favourable one judged by both maternal well-being, fetal intrauterine growth, ten-minute Apgar score and perinatal mortality. At birth the concentration of metoprolol shows a ratio of 1:1 between maternal plasma and umbilical plasma and furthermore the ratio between maternal plasma and breast milk is 1:4. The newborns of mothers on beta-blocking therapy did not differ from those of mothers on hydralazine regarding heart rate, plasma glucose or plasma bilirubin. These data indicate that fetal danger from selective beta-blocking agents during pregnancy may have been overestimated.

  16. The Role of Beta-Blockers in the Treatment of Hypertension.

    Science.gov (United States)

    Cruickshank, John M

    2017-01-01

    angiotensin receptor blockers (ARBs)) do not decrease (and may increase) the risk of myocardial infarction, and are therefore inappropriate first-line agents in this age-group. By contrast, in younger/middle-aged hypertensive subjects (less than 60 years old), meta-analysis has shown that beta-blockers are significantly superior to randomised placebo, and at least as effective as randomised comparator agents, in reducing death/stroke/myocardial infarction. In this younger/middle-aged hypertensive group beta-blockers have been shown (vs randomised placebo or diuretics) to reduce the risk of myocardial infarction by 35-50 %, and stroke by 50-55 % (vs placebo), in non-smoker men. Atenolol was at least as effective as ACE-inhibition (captopril) in reducing all 7 cardiovascular endpoints (including stroke which was reduced by 50 %), vs less tight control of blood pressure, in obese hypertensive subjects with type-2 diabetes (UKPDS study); and after 20 years follow-up, atenolol was significantly (23 %) superior to the ACE-inhibitor in reducing the risk of all-cause death (beta-blockers have anti-cancer properties, which maybe relevant). Primary/essential hypertension in younger/middle-age is underpinned by high sympathetic nerve activity. In this age-group high resting heart rates and high plasma norepinephrine levels (independent of blood pressure) are linked to premature cardiovascular events and death. Thus, anti-hypertensive agents that increase sympathetic nerve activity ie diuretics, dihydropyridine calcium blockers, and ARBs, are inappropriate first-line choices in this younger age-group. Beta-blockers perform well vs randomised placebo and other antihypertensive agents regarding reduced risk of death/stroke/myocardial infarction in younger (<60 years) hypertensive subjects, and are a reasonable first-line choice of therapy (certainly in men). These facts should be reflected in the recommendations of guideline committees around the world.

  17. [Combined therapy with quinapril, an ACE inhibitor, and valsartan, a type 1 angiotensin II receptors blocker, for moderate chronic cardiac failure may raise the degree of neurohormonal block and improve 24-h heart rate variability compared to the effect of monotherapy (data from the trial SADKO-CHF)].

    Science.gov (United States)

    Skvortsov, A A; Nasonova, S N; Sychev, A V; Arbolishvili, G N; Baklanova, N A; Mareev, V Iu; Belenkov, Iu N

    2005-01-01

    To compare effects of various regimens of long-term monotherapy with quinapril (an ACE inhibitor) and valsartan (a type 1 angiotensin II receptors blocker) and combined therapy with these drugs on the activity of heurohormonal systems and 24-h heart rate variability (HRV) in patients with stable moderate chronic cardiac failure (CCF). A total of 80 patients with FC II-III CCF secondary to coronary heart disease (CHD), delated cardiomyopathy (DCMP) and decompensated hypertensive heart (49%/47%/4%) were randomized into 3 groups. Group 1 patients (n = 28) received quinapril, group 2 (n = 26)--valsartan, group 3 (n = 26)--quinapril + valsartan. The levels of norepinephrine (NE), angiotensin II (AT II), activity of plasmic renin (PR), aldosteron (AS), plasmic cerebral sodiumuretic peptide (CSUP) were measured and ECG with determination of HRV and heart rate disturbances was made before and 3, 6 months after the treatment. NE concentration lowered most significantly in group 1 (from 630 to 405 pg/ml) vs groups 2 and 3 (from 525 to 490 pg/ml and from 525 to 480 pg/ml, respectively). A 6-month treatment induced significant changes neither in concentrations of AT II nor AC. ATII concentrations rose 2-fold in group III (from 11.9 to 24.3 pg/ml) under a parallel rise of PR activity from 0.7 to 2.5 ng/ml/h and a fall in AS level from 132 to 83 pg/ml. In group 2 AS diminished also (from 165 to 126 pg/ml). CSUP decreased in all the groups, but significantly only in groups II and III (from 350 to 237 and 322 to 204 pg/ml after 6 months of treatment, respectively). Significant changes of 24-h HRV (both spectral and temporary) were observed in group 1 after 3 months of treatment. These changes lost significance to the end of the treatment. In groups 2 and 3 the changes were less pronounced. Quinapril is more potent than valsartan and quinapril + valsartan combination in relation to activity of sympathico-adrenal system and HRV in patients with moderate stable CCF. Long-term therapy

  18. Beta-blocker under-use in COPD patients

    Directory of Open Access Journals (Sweden)

    Lim KP

    2017-10-01

    Full Text Available Kuan Pin Lim,1,2 Sarah Loughrey,1 Michael Musk,1,2 Melanie Lavender,1,2 Jeremy P Wrobel1–3 1Advanced Lung Disease Unit, Royal Perth Hospital, Perth, WA, Australia; 2Respiratory Department, Fiona Stanley Hospital, Murdoch, WA, Australia; 3School of Medicine, University of Notre Dame, Fremantle, WA, Australia Background: Cardiovascular (CVS comorbidities are common in COPD and contribute significantly to morbidity and mortality, especially following acute exacerbations of COPD (AECOPD. Beta-blockers (BBs are safe and effective in COPD patients, with demonstrated survival benefit following myocardial infarction. We sought to determine if BBs are under-prescribed in patients hospitalized with AECOPD. We also sought to determine inpatient rates of CVS and cerebrovascular complications, and their impact on patient outcomes. Methods: Retrospective hospital data was collected over a 12-month period. The medical records of all patients >40 years of age coded with a diagnosis of AECOPD were analyzed. Prevalent use and incident initiation of BBs were assessed. Comorbidities including indications and contraindications for BB use were analyzed. Results: Of the 366 eligible patients, 156 patients (42.6% had at least one indication for BB use – of these patients, only 53 (34.0% were on BB therapy and 61 (39.1% were not on BB therapy but had no listed contraindication. Prevalent use of BBs at the time of admission in all 366 patients was 19.7%, compared with 45.6%, 39.6% and 45.9% use of anti-platelets, statins and angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, respectively. CVS and cerebrovascular complications were common in this population (57 patients, 16% and were associated with longer length of stay (p<0.01 and greater inpatient mortality (p=0.02. Conclusions: BBs are under-prescribed in COPD patients despite clear indication(s for their use. Further work is required to explore barriers to BB prescribing in COPD patients

  19. 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

  20. ACT-ONE - ACTION at last on cancer cachexia by adapting a novel action beta-blocker.

    Science.gov (United States)

    Lainscak, Mitja; Laviano, Alessandro

    2016-09-01

    Novel action beta-blockers combine many different pharmacological effects. The espindolol exhibits effects through β and central 5-HT1α receptors to demonstrate pro-anabolic, anti-catabolic, and appetite-stimulating actions. In the ACT-ONE trial, espindolol reversed weight loss and improved handgrip strength in patients with cachexia due to non-small cell lung cancer or colorectal cancer. With this trial, another frontier of cachexia management is in sight. Nonetheless, more efficacy and safety data is needed before new therapeutic indications for novel action beta-blockers can be endorsed.

  1. 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

  2. Cardioprotection with beta-blockers: myths, facts and Pascal's wager.

    Science.gov (United States)

    Messerli, F H; Bangalore, S; Yao, S S; Steinberg, J S

    2009-09-01

    Beta-blockers were documented to reduce reinfarction rate more than 3 decades ago and subsequently touted as being cardioprotective for a broad spectrum of cardiovascular indications such as hypertension, diabetes, angina, atrial fibrillation as well as perioperatively in patients undergoing surgery. However, despite lowering blood pressure, beta-blockers have never shown to reduce morbidity and mortality in uncomplicated hypertension. Also, beta-blockers do not prevent heart failure in hypertension any better than any other antihypertensive drug class. Beta-blockers have been shown to increase the risk on new onset diabetes. When compared with nondiuretic antihypertensive drugs, beta-blockers increase all-cause mortality by 8% and stroke by 30% in patients with new onset diabetes. Beta-blockers are useful for rate control in patients with chronic atrial fibrillation but do not help restore sinus rhythm or have antifibrillatory effects in the atria. Beta-blockers provide symptomatic relief in patients with chronic stable angina but do not reduce the risk of myocardial infarction. Adverse effects of beta-blockers are common including fatigue, dizziness, depression and sexual dysfunction. However, beta-blockers remain a cornerstone in the management of patients having suffered a myocardial infarction and for patients with heart failure. Thus, recent evidence argues against universal cardioprotective properties of beta-blockers but attest to their usefulness for specific cardiovascular indications.

  3. High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, K.P.; Sharp, A.; Strom, M.; Kahl, S.D.

    1986-05-01

    Antibodies with high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers have been produced in rabbits by immunization with dihydropyridine-protein conjugates. Anti-dihydropyridine antibodies were found to specifically bind (/sup 3/H)nitrendipine, (/sup 3/H)-nimodipine, (/sup 3/H)nisoldipine, and (/sup 3/H)PN 200-110 (all 1,4-dihydropyridine Ca2+-channel blockers) with high affinity, while (/sup 3/H)verapamil, (/sup 3/H)diltiazem, and (/sup 3/H)trifluoperazine were not recognized. The average dissociation constant of the (/sup 3/H)nitrendipine-antibody complex was 0.06 (+/- 0.02) X 10(-9) M for an antiserum studied in detail and ranged from 0.01 to 0.24 X 10(-9) M for all antisera. Inhibition of (/sup 3/H)nitrendipine binding was specific for the 1,4-dihydropyridine Ca2+-channel modifiers and the concentrations required for half-maximal inhibition ranged between 0.25 and 0.90 nM. Structurally unrelated Ca2+-channel blockers, calmodulin antagonists, inactive metabolites of nitrendipine, and UV-inactivated nisoldipine did not modify (/sup 3/H)nitrendipine binding to the anti-dihydropyridine antibodies. Dihydropyridines without a bulky substituent in the 4-position of the heterocycle were able to displace (/sup 3/H)nitrendipine binding, but the concentrations required for half-maximal inhibition were greater than 800 nM. In summary, anti-dihydropyridine antibodies have been shown to have high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers and to exhibit dihydropyridine binding properties similar to the membrane receptor for the 1,4-dihydropyridine Ca2+-channel blockers.

  4. Differential effects of beta-blockers on albuminuria in patients with type 2 diabetes.

    Science.gov (United States)

    Bakris, George L; Fonseca, Vivian; Katholi, Richard E; McGill, Janet B; Messerli, Franz; Phillips, Robert A; Raskin, Philip; Wright, Jackson T; Waterhouse, Brian; Lukas, Mary Ann; Anderson, Karen M; Bell, David S H

    2005-12-01

    Increases in the cardiovascular risk marker microalbuminuria are attenuated by blood pressure reduction using blockers of the renin-angiotensin system. Such changes in microalbuminuria have not been observed when beta-blockers are used. A prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial was to examine the effects of different beta-blockers on changes in albuminuria in the presence of renin-angiotensin system blockade. Participants with hypertension and type 2 diabetes were randomized to either metoprolol tartrate (n=737) or carvedilol (n=498) in blinded fashion after a washout period of all antihypertensive agents except for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Blinded medication was titrated to achieve target blood pressure, with a-5 month follow-up period. The current analysis examined microalbuminuria, using spot urine albumin:creatinine, in participants who had values at screening and trial end. A greater reduction in microalbuminuria was observed for those randomized to carvedilol (-16.2%Delta; 95% confidence interval, -25.3, -5.9; P=0.003). Of those with normoalbuminuria at baseline, fewer progressed to microalbuminuria on carvedilol versus metoprolol (20 of 302 [6.6%] versus 48 of 431 [11.1%], respectively; P=0.03). Microalbuminuria development was not related to differences in blood pressure or achievement of blood pressure goal (68% carvedilol versus 67%, metoprolol). Presence of metabolic syndrome at baseline was the only independent predictor of worsening albuminuria throughout the study (P=0.004). Beta-blockers have differential effects on microalbuminuria in the presence of renin-angiotensin system blockade. These differences cannot be explained by effects on blood pressure or alpha1-antagonism but may relate to antioxidant properties of carvedilol.

  5. Impact of home patient telemonitoring on use of β-blockers in congestive heart failure.

    Science.gov (United States)

    Antonicelli, Roberto; Mazzanti, Ilaria; Abbatecola, Angela M; Parati, Gianfranco

    2010-10-01

    Congestive heart failure (CHF), which typically affects older people, is characterized by high short- and mid-term mortality rates. However, despite accumulating evidence showing that administration of β-blockers (β-adrenoceptor antagonists) can improve the clinical status of CHF patients, use of these agents in adequate dosages in this setting is not routine. One reason for this appears to be a concern about a possible risk of bradyarrhythmia associated with use of β-blockers. Telecardiology has recently been investigated as a means of constantly monitoring the heart rate of CHF patients in their homes. Its use may allay concerns about the risk of bradyarrhythmia and facilitate a more widespread use of β-blockers in this context. The primary objectives of this study were to assess the impact of telemonitoring on patients' adherence to prescribed therapeutic regimens, particularly β-blockers, and to explore whether use of home telemonitoring reduces mortality and rate of re-admission to hospital in elderly CHF patients compared with normal specialized CHF team care. A total of 57 patients with CHF (31 New York Heart Association [NYHA] class II, 23 NYHA class III and 3 NYHA class IV), with a mean ± SD age of 78.2 ± 7.3 years, were randomized to a control group who received standard care, based on routinely scheduled clinic visits, from a team specialized in CHF patient management, or to a home telemonitoring group (TM group), managed by the same specialized CHF team. Patients were followed up over 12 months. Compared with the control group, the TM group had a significant increase in the use of β-blockers, HMG-CoA reductase inhibitors (statins) and aldosterone receptor antagonists. A reduction in nitrate administration compared with baseline was also seen in the TM group. The 12-month occurrence of the primary combined endpoint of mortality and hospital re-admission for CHF was significantly lower in the TM group than in the control group (p

  6. 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 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.

  7. β-Blockers and All-Cause Mortality in Adults with Episodes of Acute Bronchitis: An Observational Study.

    Directory of Open Access Journals (Sweden)

    Frans H Rutten

    Full Text Available Recent observational studies suggest that β-blockers may improve long-term prognosis in patients with chronic obstructive pulmonary disease (COPD. We assessed whether β-blocker use improves all-cause mortality in patients with episodes of acute bronchitis.An observational cohort study using data from the electronic medical records of 23 general practices in the Netherlands. The data included standardized information about daily patient contacts, diagnoses, and drug prescriptions. Cox regression was applied with time-varying treatment and covariates.The study included 4,493 patients aged 45 years and older, with at least one episode of acute bronchitis between 1996 and 2006. The mean (SD age of the patients was 66.9 (11.7 years, and 41.9% were male. During a mean (SD follow up period of 7.7 (2.5 years, 20.4% developed COPD. In total, 22.7% had cardiovascular comorbidities, resulting in significant higher mortality rates than those without (51.7% vs. 12.0%, p<0.001. The adjusted hazard ratio of cardioselective β-blocker use for mortality was 0.62 (95% confidence interval [CI], 0.50-0.77, and 1.01 (95% CI 0.75-1.36 for non-selective ones. Some other cardiovascular drugs also reduced the risk of mortality, with adjusted HRs of 0.60 (95% CI 0.46-0.79 for calcium channel blockers, 0.88 (95% CI 0.73-1.06 for ACE inhibitors/angiotensin receptor blockers, and 0.42 (95% CI 0.31-0.57 for statins, respectively.Cardiovascular comorbidities are common and increase the risk of mortality in adults with episodes of acute bronchitis. Cardioselective β-blockers, but also calcium channel blockers and statins may reduce mortality, possibly as a result of cardiovascular protective properties.

  8. Preliminary study of beta-blocker therapy on modulation of interleukin-33/ST2 signaling during ventricular remodeling after acute myocardial infarction.

    Science.gov (United States)

    Xia, Jinggang; Qu, Yang; Yin, Chunlin; Xu, Dong

    2017-01-01

    This study aimed to evaluate the role of b-blocker therapy on modulating interleukin (IL)-33/ST2 (interleukin-1 receptor-like 1) signaling during ventricular remodeling related to heart failure (HF) after acute myocardial infarction (AMI). Sprague-Dawley rats that survived surgery to induce AMI were randomly divided into the placebo group and the b-blocker treatment group. A sham group was used as a control. Left ventricular (LV) function variables, the myocardial infarct size, fibrosis and IL-33/ST2 protein expression was measured. Compared with the placebo group, b-blocker treatment significantly improved LV function and reduced infarct size (p blocker treatment (p > 0.05), however, treatment with b-blocker enhanced IL-33/ST2 signaling, with lower expression of sST2 (p blocker therapy might play a beneficial role in the modula-tion of IL-33/ST2 signaling during ventricular remodeling. These results may be helpful in identifying IL-33/ST2 systems as putative b-blocker targets at an early stage after AMI. (Cardiol J 2017; 24, 2: 188-194).

  9. Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy.

    Science.gov (United States)

    Wang, H M; Liao, Z X; Komaki, R; Welsh, J W; O'Reilly, M S; Chang, J Y; Zhuang, Y; Levy, L B; Lu, C; Gomez, D R

    2013-05-01

    Preclinical studies have shown that norepinephrine can directly stimulate tumor cell migration and that this effect is mediated by the beta-adrenergic receptor. We retrospectively reviewed 722 patients with non-small-cell lung cancer (NSCLC) who received definitive radiotherapy (RT). A Cox proportional hazard model was utilized to determine the association between beta-blocker intake and locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). In univariate analysis, patients taking beta-blockers (n = 155) had improved DMFS (P beta-blockers (n = 567). In multivariate analysis, beta-blocker intake was associated with a significantly better DMFS [hazard ratio (HR), 0.67; P = 0.01], DFS (HR, 0.74; P = 0.02), and OS (HR, 0.78; P = 0.02) with adjustment for age, Karnofsky performance score, stage, histology type, concurrent chemotherapy, radiation dose, gross tumor volume, hypertension, chronic obstructive pulmonary disease and the use of aspirin. There was no association of beta-blocker use with LRPFS (HR = 0.91, P = 0.63). Beta-blocker use is associated with improved DMFS, DFS, and OS in this large cohort of NSCLC patients. Future prospective trials can validate these retrospective findings and determine whether the length and timing of beta-blocker use influence survival outcomes.

  10. Utilization of Beta blockers post-myocardial infarction.

    Science.gov (United States)

    Ong, W M; Che Zuraini, S; Wan Azman, W A; Rajasuriar, R

    2013-01-01

    Beta blockers provide both morbidity and mortality benefits for post-myocardial infarction (MI) patients. Despite this, beta blockers are still often underused or used at suboptimal dosages. This was a retrospective observational study with the objectives of estimating the proportion of post-MI patients who are receiving beta-blocker therapy in University Malaya Medical Centre (UMMC), assessing the number of them receiving beta blockers at optimal dosages and determining the factors associated with beta-blocker prescribing post-MI. Of 315 patient case notes reviewed, 77.5% were prescribed beta blockers. However, dosages were optimized in only 39.3% of patients. Reasons for not optimizing the dosages were typically not due to the presence of contraindications to beta blockers. Elderly (> 65 years old), ejection fraction (EF) digoxin or anti-asthmatic agents were all significantly associated with a reduced rate of beta-blocker prescribing post-MI. More effort should be placed in improving its use in specific patient populations. Initiatives to optimize the dosage of beta blockers to recommended dosages that matched those in clinical trials with proven mortality benefits will also need to be intensified.

  11. 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.

  12. 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.

  13. 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

    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......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...... 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...

  14. 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...

  15. 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?

    Science.gov (United States)

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

    2010-08-01

    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 for research are identified. It is suggested that trials are designed specifically to address prognosis and treatment in this growing population.

  16. Evaluation of the Counter-regulatory Responses to Hypoglycemia in Patients with Type 1 Diabetes during Opiate Receptor Blockade with Naltrexone

    DEFF Research Database (Denmark)

    Naik, Sarita; Belfort-DeAguiar, Renata; Sejling, Anne-Sophie

    2017-01-01

    AIMS: Hypoglycemia is the major limiting factor in achieving optimal glycemic control in people with type 1 diabetes (T1DM), especially intensively treated patients with impaired glucose counterregulation during hypoglycemia. Naloxone, an opiate receptor blocker, has been reported to enhance...... responses were observed. CONCLUSION: In contrast to the intravenous opiate receptor blocker naloxone, overnight administration of the oral long acting opiate receptor blocker, naltrexone, at a clinically used dose, had a limited effect on the counterregulatory response to hypoglycemia in intensively treated...

  17. The relationship between antihypertensive combination therapies comprising diuretics and/or beta-blockers and the risk of new-onset diabetes: a retrospective longitudinal cohort study.

    Science.gov (United States)

    Liou, Yi-Sheng; Ma, Tsochiang; Tien, Liyun; Lin, Chieh-Min; Jong, Gwo-Ping

    2009-06-01

    We investigate the associations of antihypertensive drugs in double and triple combination regimens comprising diuretics and/or beta-blockers on the development of new-onset diabetes (NOD). This study was a retrospective cohort study carried out using data from claim forms provided to the central regional branch of the Bureau of National Health Insurance (BNHI) in Taiwan from January 2001 to December 2006. We estimated the odds ratios (ORs) of NOD associated with antihypertensive combination therapy use; non-NOD individuals served as the reference group. A total of 2361 NOD cases were identified among the 12,386 hypertensive patients (6143 men and 6243 women, aged 28-86 years (mean age: 68+11)) during the study period. The risk of NOD was higher after adjusting for age and sex among users of double combinations of diuretics plus beta-blockers (adjusted OR, 1.25; 95% confidence interval (CI): 1.12-1.58), diuretics plus calcium channel blockers (CCBs; adjusted OR: 1.14; 95% CI: 1.06-1.26) and beta-blockers plus calcium channel blockers (adjusted OR: 1.12; 95% CI: 1.04-1.29) than that among non-users. Patients who took angiotensin-converting enzyme (ACE) inhibitors, or alpha-blockers as part of a double-drug regimen were at a lower risk of developing NOD than were non-users. Double- or triple-drug combinations comprising angiotensin receptor blockers (ARBs) and vasodilators were not associated with risk of NOD. The results of this study suggest that users of double-drug combination therapies containing diuretics and/or beta-blockers and an ACE inhibitor or alpha-blocker are at a significantly lower risk of developing NOD than are other classes.

  18. Human CB1 Receptor Isoforms, present in Hepatocytes and ?-cells, are Involved in Regulating Metabolism

    OpenAIRE

    Isabel González-Mariscal; Krzysik-Walker, Susan M.; Doyle, Máire E; Qing-Rong Liu; Raffaello Cimbro; Sara Santa-Cruz Calvo; Soumita Ghosh; Łukasz Cieśla; Ruin Moaddel; Carlson, Olga D.; Witek, Rafal P.; Jennifer F. O’Connell; Josephine M Egan

    2016-01-01

    Therapeutics aimed at blocking the cannabinoid 1 (CB1) receptor for treatment of obesity resulted in significant improvements in liver function, glucose uptake and pancreatic ?-cell function independent of weight loss or CB1 receptor blockade in the brain, suggesting that peripherally-acting only CB1 receptor blockers may be useful therapeutic agents. Neuropsychiatric side effects and lack of tissue specificity precluded clinical use of first-generation, centrally acting CB1 receptor blockers...

  19. Microvascular obstruction after successful fibrinolytic therapy in acute myocardial infarction. Comparison of reteplase vs reteplase+abciximab: A cardiovascular magnetic resonance study.

    Science.gov (United States)

    Zoni, Antonello; Knoll, Peter; Gherli, Tiziano

    2006-01-01

    BACKGROUND.: About one third of patients with TIMI 3 after reperfusion have evidence of microvascular obstruction (MO) which represents an independent predictor of myocardial wall rupture. This explains all efforts made to prevent MO. Magnetic resonance imaging (MRI) has proved to be particularly useful in detecting MO. The aim of this study was to evaluate with MRI if different fibrinolytic regimens in acute myocardial infarction display different effects on left ventricle (LV) volumes and ejection fraction (EF), as well as on myocardial infarct size (MIsz) and MO. METHODS.: Twenty male patients, mean age 58 years, affected by acute myocardial infarction, ten anterior and ten inferior, were treated with: full dose reteplase in ten, and half dose reteplase plus full dose abciximab (R+Abcx) in the other ten patients. In the fourth day after hospital admission, MRI STIR T2 images were used to quantify MIsz, while 2dflash cineloops were used after the injection of gadolinium, to quantify LV volumes, EF and to detect MO. RESULTS.: LV EF was higher in R+Abcx 51±10 than in reteplase 41±8. MIsz was similar in both treatment groups: however a close relationship was present between MIsz and EF in the reteplase group indicating that the greater the MIsz the lower the EF. In R+Abcx this relationship was no longer present, suggesting a protective effect of the drug on microcirculation. In fact extensive MO was present in 25% of all cases, 80% of which in the reteplase group while only 20% in R+Abcx. CONCLUSION.: R+Abcx prevents MO: compared to traditional fibrinolytic therapy it allows better LV function and most likely improved long term survival.

  20. Microvascular obstruction after successful fibrinolytic therapy in acute myocardial infarction. Comparison of reteplase vs reteplase+abciximab: A cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Tiziano Gherli

    2010-05-01

    Full Text Available Background. About one third of patients with TIMI 3 after reperfusion have evidence of microvascular obstruction (MO which represents an independent predictor of myocardial wall rupture. This explains all efforts made to prevent MO. Magnetic resonance imaging (MRI has proved to be particularly useful in detecting MO. The aim of this study was to evaluate with MRI if different fibrinolytic regimens in acute myocardial infarction display different effects on left ventricle (LV volumes and ejection fraction (EF, as well as on myocardial infarct size (MIsz and MO. Methods. Twenty male patients, mean age 58 years, affected by acute myocardial infarction, ten anterior and ten inferior, were treated with: full dose reteplase in ten, and half dose reteplase plus full dose abciximab (R+Abcx in the other ten patients. In the fourth day after hospital admission, MRI STIR T2 images were used to quantify MIsz, while 2dflash cineloops were used after the injection of gadolinium, to quantify LV volumes, EF and to detect MO. Results. LV EF was higher in R+Abcx 51±10 than in reteplase 41±8. MIsz was similar in both treatment groups: however a close relationship was present between MIsz and EF in the reteplase group indicating that the greater the MIsz the lower the EF. In R+Abcx this relationship was no longer present, suggesting a protective effect of the drug on microcirculation. In fact extensive MO was present in 25% of all cases, 80% of which in the reteplase group while only 20% in R+Abcx. Conclusion. R+Abcx prevents MO: compared to traditional fibrinolytic therapy it allows better LV function and most likely improved long term survival.

  1. 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 ...

  2. Perioperative beta blockers in patients having non-cardiac surgery

    DEFF Research Database (Denmark)

    Bangalore, Sripal; Wetterslev, Jørn; Pranesh, Shruthi

    2008-01-01

    American College of Cardiology and American Heart Association (ACC/AHA) guidelines on perioperative assessment recommend perioperative beta blockers for non-cardiac surgery, although results of some clinical trials seem not to support this recommendation. We aimed to critically review the evidence...... to assess the use of perioperative beta blockers in patients having non-cardiac surgery....

  3. Biomarker Responses to Beta Blocker Exposures in Marine Bivalves

    Science.gov (United States)

    Increased consumption and improper disposal of prescription medication, such as beta (β)-blockers, contribute to their introduction into waterways and pose threats to non-target aquatic organisms. Beta-blockers are widely prescribed for medical treatment of hypertension and ...

  4. NEW ADVANCES IN BETA-BLOCKER THERAPY IN HEART FAILURE

    Directory of Open Access Journals (Sweden)

    Vincenzo eBarrese

    2013-11-01

    Full Text Available The use of -blockers (BB in heart failure (HF has been considered a contradiction for many years. Considering HF simply as a state of inadequate systolic function, BB were contraindicated because of their negative effects on myocardial contractility. Nevertheless, evidence collected in the past years have suggested that additional mechanisms, such as compensatory neuro-humoral hyperactivation or inflammation, could participate in the pathogenesis of this complex disease. Indeed, chronic activation of the sympathetic nervous system, although initially compensating the reduced cardiac output from the failing heart, increases myocardial oxygen demand, ischemia and oxidative stress; moreover, high catecholamine levels induce peripheral vasoconstriction and increase both cardiac pre- and after-load, thus determining additional stress to the cardiac muscle (1. As a consequence of such a different view of the pathogenic mechanisms of HF, the efficacy of BB in the treatment of HF has been investigated in numerous clinical trials. Results from these trials highlighted BB as valid therapeutic tools in HF, providing rational basis for their inclusion in many HF treatment guidelines. However, controversy still exists about their use, in particular with regards to the selection of specific molecules, since BB differ in terms of adrenergic -receptors selectivity, adjunctive effects on -receptors, and effects on reactive oxygen species and inflammatory cytokines production. Further concerns about the heterogeneity in the response to , as well as the use in specific patients, are matter of debate among clinicians. In this review, we will recapitulate the pharmacological properties and the classification of BB, and the alteration of the adrenergic system occurring during HF that provide a rationale for their use; we will also focus on the possible molecular mechanisms, such as genetic polymorphisms, underlying the different efficacy of molecules

  5. Intracoronary Compared to Intravenous Bolus Abciximab during Primary Percutaneous Coronary Intervention in ST-segment Elevation Myocardial Infarction (STEMI) Patients Reduces 30-day Mortality and Target Vessel Revascularization: A Randomized Trial

    DEFF Research Database (Denmark)

    Iversen, Allan; Abildgaard, Ulrik; Galloe, Anders

    2011-01-01

    patients who underwent pPCI and had indication for abciximab to either IV or IC bolus followed by a 12-hour IV infusion. Primary end-points at 30 days were target vessel revascularization (TVR), recurrent myocardial infarction (MI) or death, and the composite of the three. Secondary end-points were...... bleeding complications. Results: The two groups (IV n = 170;IC n = 185) were similar with respect to baseline characteristics. Mortality at 30 days was 5.3% in the IV group compared to only 1.1% in the IC group (P = 0.02). TVR was performed in 9.4% in the IV group compared to 3.8% in the IC group (P = 0...... bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). Conclusion: IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30-day mortality and TVR and tends to reduce MI, compared to IV-bolus. (J Interven Cardiol 2011;24:105-111)....

  6. Fracture risk in perimenopausal women treated with beta-blockers

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Vestergaard, Peter; Kassem, Moustapha

    2004-01-01

    showed 20% lower serum osteocalcin levels (an osteoblastic marker of bone formation) in women treated with beta-blockers compared to untreated women (P femoral neck did not differ between groups. beta-Blockers may decrease the activity of bone-forming cells...... (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study....... Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture...

  7. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    Science.gov (United States)

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH

  8. Impact of beta blockers on epithelial ovarian cancer survival.

    Science.gov (United States)

    Diaz, Elena S; Karlan, Beth Y; Li, Andrew J

    2012-11-01

    Stress may promote ovarian cancer progression through mechanisms including autonomic nervous system mediators such as norepinephrine and epinephrine. Beta blockers, used to treat hypertension, block production of these adrenergic hormones, and have been associated with prolonged survival in several malignancies. We sought to determine the association between beta blocker use and epithelial ovarian cancer (EOC) disease progression and survival. We performed an institutional retrospective review of patients with EOC treated between 1996 and 2006. Patients underwent cytoreductive surgery followed by platinum-based chemotherapy. Women were considered beta blocker users if these medications were documented on at least two records more than 6 months apart. Statistical tests included Fisher's exact, Kaplan-Meier, and Cox regression analyses. 248 met inclusion criteria. 68 patients used antihypertensives, and 23 used beta blockers. Median progression-free survival for beta blocker users was 27 months, compared with 17 months for non-users (p=0.05). Similarly, overall disease-specific survival was longer for beta blocker users (56 months) compared with non-users (48 months, p=0.02, hazard ratio=0.56). Multivariate analysis identified beta blocker use as an independent positive prognostic factor, after controlling for age, stage, grade, and cytoreduction status (p=0.03). Overall survival remained longer for beta blocker users (56 months) when compared with hypertensive patients on other medications (34 months) and patients without hypertension (51 months) (p=0.007). In this cohort of patients with EOC, beta blocker use was associated with a 54% reduced chance of death compared with that of non-users. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. [Use of beta blockers in various clinical states].

    Science.gov (United States)

    Radović, Vesna V

    2011-01-01

    According to the convincing evidence, a decline in mortality rate has been achieved with beta-blockers in patients with an acute myocardial infarction and in post-infarction follow-up. In fact, there has been a clear reduction of sudden coronary death. The necessary condition for the efficiency of beta-blockers is an early use. They are also a medication of choice for angina after an infarction. The objective of this work was to evaluate the use of beta-blockers after a myocardial infarction in various clinical states and to eliminate doubts concerning their prescription. Even in conditions considered contraindications for administration of beta blockers such as old age, diabetes, non-Q-wave myocardial infarction, peripheral vascular disease, arterial disease, heart insufficiency; ventricular arrhythmias, renal disease, chronic obstructive pulmonary disease, asthma and depression, patients benefit from beta blockers when they are given along with a right choice of the medication and a regular followup of the patient. Preference is given to cardioselective beta blockers in patients with diabetes or lung disease. Beta-blockers do not cause long-term lipid alterations. Therefore, the matter of clinically significant alterations of lipids or blood glucose levels should not need further consideration as a problem of the treatment of diabetics. Investigations have proved that the use of beta-blockers reduces the development of cerebrovascular accidents, heart insufficiency and hypertension. Despite strong arguments and numerous recommendations, beta-blockers have not been accepted to a sufficient extent as an integral part of treatment of acute coronary syndrome and related diseases, to the detriment of many lost lives and in spite of favourable pharmaco-economic aspect.

  10. Beta-blocker usage and breast cancer survival: a nested case-control study within a UK clinical practice research datalink cohort.

    Science.gov (United States)

    Cardwell, Chris R; Coleman, Helen G; Murray, Liam J; Entschladen, Frank; Powe, Des G

    2013-12-01

    To investigate the association between post-diagnostic beta-blocker usage and risk of cancer-specific mortality in a large population-based cohort of female breast cancer patients. A nested case-control study was conducted within a cohort of breast cancer patients identified from cancer registries in England(using the National Cancer Data repository) and diagnosed between 1998 and 2007. Patients who had a breast cancer-specific death(ascertained from Office of National Statistics death registration data) were each matched to four alive controls by year and age at diagnosis. Prescription data for these patients were available through the Clinical Practice Research Datalink. Conditional logistic regression models were used to investigate the association between breast cancer-specific death and beta-blocker usage. Post-diagnostic use of beta-blockers was identified in 18.9% of 1435 breast cancer-specific deaths and 19.4% of their 5697 matched controls,indicating little evidence of association between beta-blocker use and breast cancer-specific mortality [odds ratio (OR) = 0.97,95% confidence interval (CI) 0.83, 1.13]. There was also little evidence of an association when analyses were restricted to cardio non-selective beta-blockers (OR = 0.90, 95% CI 0.69, 1.17). Similar results were observed in analyses of drug dosage frequency and duration, and beta-blocker type. In this large UK population-based cohort of breast cancer patients,there was little evidence of an association between post-diagnostic beta-blocker usage and breast cancer progression. Further studies which include information on tumour receptor status are warranted to determine whether response to beta-blockers varies by tumour subtypes.

  11. Use of beta blockers in various clinical states

    OpenAIRE

    Radović Vesna V.

    2011-01-01

    Introduction. According to the convincing evidence, a decline in mortality rate has been achieved with beta-blockers in patients with an acute myocardial infarction and in post-infarction follow-up. In fact, there has been a clear reduction of sudden coronary death. The necessary condition for the efficiency of beta-blockers is an early use. They are also a medication of choice for angina after an infarction. The objective of this work was to evaluate the use of beta-blockers after a my...

  12. Calcium channel blockers shorten the periodicity of ultradian variation in blood pressure in patients with essential hypertension.

    Science.gov (United States)

    Kawamura, H; Mitsubayashi, H; Saito, T; Kanmatsuse, K; Saito, N

    1998-09-01

    We studied ultradian and circadian variations in blood pressure (BP) in patients with essential hypertension who were receiving antihypertensive agents. No patient had previously received antihypertensive agents before this study began. After a 2-wk control period, we performed ambulatory blood pressure monitoring (ABPM) in 86 patients with essential hypertension (WHO stages I or II). The patients were then given a long-acting angiotensin converting enzyme inhibitor (ACEI) (captopril or imidapril), a beta-receptor blocker (arotinolol or bisoprolol), or a calcium channel blocker (nisoldipine or benidipine) twice daily to control BP. We evaluated the patients' BP once every 2 wk to ensure optimal control. After 12 wk, ultradian and circadian variations in BP were analyzed by the maximum entropy method (MEM). All antihypertensive agents decreased office systolic BP (SBP), office diastolic BP (DBP), 24-h SBP, and 24-h DBP. ACEI did not change office, 24-h, daytime, or nighttime pulse rate (PR). Arotinolol and bisoprolol decreased 24-h PR. All antihypertensive agents decreased 24-h, daytime, and nighttime pressure rate product. MEM showed that no antihypertensive agent affected the circadian variation in the 1st peak (24-h periodicity) of SBP, DBP, or PR. However, calcium channel blockers shortened the periodicity of circadian variations in the 2nd peak (12-h periodicity) of SBP and the 3rd peak (8 to 6 h periodicity) of SBP. Therefore, ultradian variations in BP should be carefully monitored in hypertensive patients treated with calcium channel blockers.

  13. [Qianlieping capsule plus alpha-blocker for chronic non-bacterial prostatitis: analysis of 220 cases].

    Science.gov (United States)

    Li, Jian-Ping; Chong, Tie; Chen, Hai-Wen; Li, He-Cheng; Cao, Jun; Zhang, Peng; Li, Hong-Liang

    2012-09-01

    To investigate the clinical effects of Qianlieping Capsule combined with alpha-receptor blocker tamsulosin on chronic non-bacterial prostatitis (CNBP). We assigned 220 CNBP patients to three groups to receive oral Qianlieping Capsule (2.0 g tid) plus alpha-receptor blocker tamsulosin (0.2 mg qd) (n = 98), Qianlieping Capsule alone at 2.0 g tid (n = 66), and tamsulosin alone at 0.2 mg qd (n = 56) , respectively. After 6 weeks of medication, we assessed the therapeutic effects according to the NIH-CPSI scores and the number of small particles of lecithin (SPL) in the prostatic fluid after treatment. Qianlieping Capsule alone increased the number of SPL by 46.9% and reduced the NIH-CPSI score by 24.4%. Combination of Qianlieping and tamsulosin more significantly increased the number of SPL (61.4%) and decreased the NIH-CPSI score (42.3%) than tamsulosin alone (33.7% and 28.6%) (P Capsule chronic is effective for chronic non-bacterial prostatitis, and the combination of Qianlieping Capsule with tamsulosin produces even better effect than tamsulosin alone.

  14. Beta Blockers and Breast Cancer Mortality: A Population- Based Study

    National Research Council Canada - National Science Library

    Thomas I. Barron; Roisin M. Connolly; Linda Sharp; Kathleen Bennett; Kala Visvanathan

    2011-01-01

    .... A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer-specific mortality...

  15. 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....

  16. Beta blockers after myocardial infarction: have trials changed practice?

    Science.gov (United States)

    Baber, N S; Julian, D G; Lewis, J A; Rose, G

    1984-11-24

    A survey of British consultant cardiologists was carried out to elicit their current practices when prescribing long term beta blockers after myocardial infarction. Sixty (72%) of the respondents reported that they used beta blockers prophylactically even in the absence of any other indications; the details of their stated policies, however, varied considerably. The favourable evidence of clinical trials in this indication appears to have been assimilated into hospital practice.

  17. Beta blockers after myocardial infarction: have trials changed practice?

    OpenAIRE

    Baber, N S; Julian, D. G.; Lewis, J A; Rose, G

    1984-01-01

    A survey of British consultant cardiologists was carried out to elicit their current practices when prescribing long term beta blockers after myocardial infarction. Sixty (72%) of the respondents reported that they used beta blockers prophylactically even in the absence of any other indications; the details of their stated policies, however, varied considerably. The favourable evidence of clinical trials in this indication appears to have been assimilated into hospital practice.

  18. BETA-BLOCKERS IN THE TREATMENT OF ARTERIAL HYPERTENSION: EVIDENCE BASED DATA AND REAL PRACTICE

    OpenAIRE

    M. V. Leonova

    2012-01-01

    Data of the largest meta-analyzes of beta-blockers use in arterial hypertension is presented. The role of beta-blockers among other basic groups of antihypertensive drugs (thiazide diuretics, calcium channel blockers, ACE inhibitors) is evaluated. Special considerations of beta-blockers use in hypertensive patients with diabetes mellitus and chronic heart failure are discussed. Special attention is paid to bisoprolol.

  19. BETA-BLOCKERS IN THE TREATMENT OF ARTERIAL HYPERTENSION: EVIDENCE BASED DATA AND REAL PRACTICE

    OpenAIRE

    M. V. Leonova

    2015-01-01

    Data of the largest meta-analyzes of beta-blockers use in arterial hypertension is presented. The role of beta-blockers among other basic groups of antihypertensive drugs (thiazide diuretics, calcium channel blockers, ACE inhibitors) is evaluated. Special considerations of beta-blockers use in hypertensive patients with diabetes mellitus and chronic heart failure are discussed. Special attention is paid to bisoprolol.

  20. Severe beta blocker and calcium channel blocker overdose: Role of high dose insulin.

    Science.gov (United States)

    Seegobin, Karan; Maharaj, Satish; Deosaran, Ansuya; Reddy, Pramod

    2018-01-10

    A 54-year-old female presented after taking an overdose of an unknown amount of hydrochlorothiazide, doxazocin, atenolol and amlodipine. She was initially refractory to treatment with conventional therapy (intravenous fluids, activated charcoal, glucagon 5 mg followed with glucagon drip, calcium gluconate 10%, and atropine). Furthermore, insulin at 4 U/kg was not effective in improving her hemodynamics. Shortly after high dose insulin was achieved with 10 U/kg, there was dramatic improvement in hemodynamics resulting in three of five vasopressors being weaned off in 8 h. She was subsequently off all vasopressors after six additional hours. The role of high dose insulin has been documented in prior cases, however it is generally recommended after other conventional therapies have failed. However, there are other reports that suggest it as initial therapy. Our patient failed conventional therapies and responded well only with maximum dose of insulin. Physicians should consider high dose insulin early in severe beta blocker or calcium channel blocker overdose for improvement in hemodynamics. This leads to early discontinuation of vasopressors. It is important that emergency physicians be aware of the beneficial effects of high dose insulin when initiated early as opposed to waiting for conventional therapy to fail; as these patients often present first to the emergency department. Early initiation in the emergency department can be beneficial in these patients. Copyright © 2018. Published by Elsevier Inc.

  1. Beta-blockers: friend or foe in asthma?

    Directory of Open Access Journals (Sweden)

    Arboe B

    2013-07-01

    Full Text Available Bente Arboe, Charlotte Suppli UlrikDepartment of Pulmonary Medicine, Hvidovre Hospital and University of Copenhagen, Hvidovre, DenmarkBackground and aim: 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.Method: Systematic literature review.Results: No significant increase in the number of patients requiring rescue oral corticosteroid for an exacerbation of asthma has been observed after initiation of β-blocker treatment. Patients with mild to moderate reactive airway disease, probably both asthma and chronic obstructive pulmonary disease, may have a limited fall in forced expiratory volume in 1 second (FEV1 following single-dose administration of β-blocker, whereas no change in FEV1 has been reported following long-term administration. In a murine model of asthma, long-term administration of β-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect. In keeping with this, long-term administration of a nonselective β-blocker to steroid-naïve asthma patients has shown a dose-dependent improvement in airway hyperresponsiveness, and either an asymptomatic fall in FEV1 or no significant change in FEV1. Furthermore, available studies show that bronchoconstriction induced by inhaled methacholine is reversed by salbutamol in patients on regular therapy with a β-blocker. On the other hand, a recent placebo-controlled trial of propranolol and tiotropium bromide added to inhaled corticosteroids revealed no effect on airway hyperresponsiveness and a small, not statistically significant, fall in FEV1 in patients classified as having mild to moderate asthma.Conclusion: The available, although limited, evidence suggests that a dose-escalating model of β-blocker therapy to patients with asthma is well tolerated, does not

  2. 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

  3. Real role of β-blockers in regression of left ventricular mass in hypertension patients

    Science.gov (United States)

    Xing, FuWei; Chen, Jialin; Zhao, BinLiang; Jiang, Jingzhou; Tang, Anli; Chen, Yili

    2017-01-01

    Abstract Background: Left ventricular hypertrophy (LVH) is commonly present in patients with hypertension (HT). According to the expert consensus document from American, angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) were recommended as 1st-line therapeutic drugs. However, none noticed the different efficacy between fat-soluble and selective β1-receptor blockers (FS-β-B) and other β-blockers on regression of LVH before. The aim of this analysis was to compare the efficacy of FS-β-B with the other 4 different classes of antihypertensive drugs (ACEI, ARBs, calcium channel blockers [CCBs], and diuretics) on regression of LVH. Methods: Relative trials were identified in the PubMed, Web of Science, OVID EBM Reviews and Cochrane databases, and the relevant papers were examined. We performed both traditional and Bayesian meta-analysis of randomized controlled trials (RCTs) about the regression of LVH. Sensitivity analysis and regression analysis were performed to explore possible sources of heterogeneity. Inconsistency analysis was performed to check whether the analysis of the trials in the network was indeed consistent. Results: A total of 41 RCTs involving 2566 patients with HT and LVH were included in this analysis. Bayesian network meta-analysis indicated no statistically significant differences between these groups: FS-β-B and ACEI (MD, −7.09; 95% CI, −14.99, 1.27); FS-β-B and ARB (MD, −2.66; 95% Cl, −12.02, 6.31). Although FS-β-B showed greater efficacy when compared with diuretic (MD, 13.04; 95% CI, 3.38, 22.59) or CCB (MD, 10.90; 95% CI, 1.98, 19.49). The probabilities of being among the most efficacious treatments were: FS-β-B (72%), ARB (27%), ACEI (0.01%), CCB (0.00%), and diuretic (0.00%). Conclusion: Evidence from our analysis reveals that FS-β-B have potential to become 1st-line therapeutic drugs in HT and LVH patients. However, the real efficacy of FS-β-B on regression of LVH should be confirmed by

  4. Calcium channel blockers for inhibiting preterm labour and birth.

    Science.gov (United States)

    Flenady, Vicki; Wojcieszek, Aleena M; Papatsonis, Dimitri N M; Stock, Owen M; Murray, Linda; Jardine, Luke A; Carbonne, Bruno

    2014-06-05

    Preterm birth is a major contributor to perinatal mortality and morbidity, affecting around 9% of births in high-income countries and an estimated 13% of births in low- and middle-income countries. Tocolytics are drugs used to suppress uterine contractions for women in preterm labour. The most widely used tocolytic are the betamimetics, however, these are associated with a high frequency of unpleasant and sometimes severe maternal side effects. Calcium channel blockers (CCBs) (such as nifedipine) may have similar tocolytic efficacy with less side effects than betamimetics. Oxytocin receptor antagonists (ORAs) (e.g. atosiban) also have a low side-effect profile. To assess the effects on maternal, fetal and neonatal outcomes of CCBs, administered as a tocolytic agent, to women in preterm labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 November 2013). All published and unpublished randomised trials in which CCBs were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation. Two review authors independently assessed trial eligibility, undertook quality assessment and data extraction. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with the 95% confidence interval (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) were calculated for categorical outcomes that were statistically significantly different. This update includes 26 additional trials involving 2511 women, giving a total of 38 included trials (3550 women). Thirty-five trials used nifedipine as the CCB and three trials used nicardipine. Blinding of intervention and outcome assessment was undertaken in only one of the trials (a placebo controlled trial). However, objective outcomes defined according to timing of birth and perinatal mortality were considered to have low risk of detection bias.Two small trials comparing CCBs

  5. Effects of calcium channel blocker-based combinations on intra-individual blood pressure variability: post hoc analysis of the COPE trial

    Science.gov (United States)

    Umemoto, Seiji; Ogihara, Toshio; Matsuzaki, Masunori; Rakugi, Hiromi; Ohashi, Yasuo; Saruta, Takao; Ogihara, T; Saruta, T; Matsuzaki, M; Eto, T; Fujita, T; Higaki, J; Ito, S; Kamiya, A; Kikuchi, K; Matsuoka, H; Suzuki, H; Tei, C; Matsuoka, H; Kumagai, H; Ohashi, Y; Rakugi, H; Shimamoto, K; Takishita, S; Umemoto, S; Shimada, K; Hayashi, K; Kario, K; Kawana, M; Kitagawa, K; Makino, H; Matsumoto, M; Yoshikawa, J; Abe, K; Matsuura, H; Ohashi, Y; Otsuka, K; Tanabe, K; Suzuki, N; Nogawa, S; Utsunomiya, K; Yoshikawa, T; Yumura, W; Ohashi, Y; Umemoto, S; Kikuchi, K; Hasebe, N; Bunya, M; Fujii, W; Funayama, N; Gima, M; Hashizume, K; Hirayama, Y; Matsuhashi, H; Morimoto, H; Myojo, T; Ohori, K; Omiya, H; Ota, T; Sato, A; Shiokoshi, T; Tanaka, H; Yamazaki, K; Yoshie, H; Shimamoto, K; Abiru, M; Adachi, M; Fujise, Y; Hanawa, K; Ishii, K; Kadono, Y; Kaku, T; Kaneta, S; Kato, M; Kato, N; Kobayashi, H; Komakine, T; Matsumoto, T; Mita, T; Miura, N; Mukai, H; Nagao, K; Nakagawa, H; Nakagawa, M; Nakajima, N; Nishimiya, T; Nishino, Y; Nunokawa, A; Ohata, J; Ooiwa, H; Sato, R; Satoh, S; Shibata, S; Takada, M; Takagawa, Y; Takagi, Y; Takeichi, S; Tanaka, S; Togashi, N; Ura, N; Wakabayashi, C; Yoshida, D; Yoshida, H; Yoshida, K; Kitabatake, A; Tsutsui, H; Akutsu, M; Fujii, S; Furumoto, T; Kakinoki, S; Kawasaki, H; Kimura, T; Makiguchi, M; Matsuo, H; Okamoto, H; Oyama, Y; Shimokawa, J; Tsuzuki, N; Ito, S; Imai, Y; Domon, R; Ebina, H; Egawa, S; Haruyama, T; Hashimoto, H; Hayakawa, T; Inomata, H; Katahira, Y; Katakura, T; Kikuchi, R; Kimura, H; Kyogoku, S; Kyogoku, Y; Matsuo, K; Nakazawa, H; Odakura, H; Okuguchi, F; Ohtomo, E; Ouchi, H; Seino, M; Tadokoro, M; Tanno, Y; Uchida, N; Yamanaka, T; Yunomura, K; Okumura, K; Hatayama, T; Kanehira, Y; Kaneko, H; Kimura, M; Maeda, N; Mikuniya, A; Narita, H; Ono, M; Osanai, T; Sato, M; Yoshino, H; Momomura, S; Ono, M; Inoue, M; Iwase, T; Miyazaki, K; Taki, M; Aizawa, T; Hasunuma, Y; Makino, H; Okabayashi, H; Hosoda, S; Sumiyoshi, T; Abe, M; Kira, Y; Nagayama, M; Sakai, K; Yoshikawa, O; Ide, M; Kimura, N; Matsuzaka, S; Miyajima, Y; Sawai, K; Sumi, T; Takada, R; Toma, M; Yamada, Y; Yoda, K; Yokokawa, T; Yokoyama, S; Kanmatsuse, K; Kushiro, T; Anazawa, T; Ebuchi, T; Fujita, H; Katsumata, N; Masubuchi, K; Migita, T; Osada, T; Otsuka, Y; Saito, F; Shimoda, S; Sugino, K; Takahashi, A; Tani, S; Yumi, K; Daida, H; Arino, T; Iesaki, T; Inomata, Y; Nakahara, H; Shiraishi, H; Sudo, H; Degawa, T; Araki, T; Itaya, H; Komatsu, H; Kuwana, H; Mikawa, T; Nomoto, H; Ogawa, N; Sato, H; Takase, H; Toyoda, H; Yamamoto, M; Obayashi, K; Akabane, I; Hamamoto, H; Kanbara, R; Kato, H; Kimura, H; Mori, N; Yamada, K; Yamamuro, M; Isobe, M; Emoto, H; Inaba, O; Inazawa, T; Inomata, H; Isobe, K; Ito, Y; Komura, M; Kosuge, H; Maejima, Y; Miwa, N; Nishimori, T; Otomo, K; Sakurai, K; Sawada, M; Seya, M; Shimizu, M; Takagi, T; Tamura, M; Tanaka, K; Tezuka, D; Tokunaga, T; Yagishita, A; Yamashina, A; Hara, T; Hayashi, S; Hirayama, Y; Hirooka, Y; Iitaka, M; Ishiyama, T; Kijima, F; Kobayashi, H; Kobayashi, Y; Kondo, K; Kuwabara, T; Mugishima, M; Nakayama, Y; Nishizato, Y; Osamura, Y; Sakomura, Y; Saneshige, S; Shindo, N; Takao, N; Takata, Y; Tomiyama, H; Ishimaru, S; Obitsu, Y; Shigematsu, H; Baba, T; Fukushima, H; Hirayama, T; Magari, K; Makimura, S; Nagae, T; Osada, K; Osada, T; Shimizu, T; Suesada, H; Tamura, K; Yamazaki, T; Hirai, A; Fukasawa, T; Ono, H; Yamakado, M; Shiba, T; Otomi, S; Uehata, A; Takazawa, K; Aizawa, A; Iketani, T; Kino, M; Kobayashi, H; Morishima, T; Sakamoto, N; Sakamoto, T; Yamakawa, H; Kasanuki, H; Nagai, R; Kadowaki, T; Tanaka, J; Yamazaki, T; Takagi, M; Ui, S; Baba, S; Fujita, K; Hasegawa, T; Tajima, K; Tanaka, M; Yamato, N; Kuwajima, I; Harada, K; Miyata, H; Mizuno, S; Ueda, S; Sugi, K; Ando, H; Mishima, K; Moroi, M; Nishizawa, S; Suzuki, S; Yamazaki, J; Nakanishi, R; Nakano, H; Tokuyasu, K; Aoyagi, T; Fujioka, M; Kobayakawa, N; Nakajima, K; Hirayama, A; Tsukamoto, K; Araki, Y; Hara, H; Hara, K; Saruya, T; Umemura, S; Arima, M; Endo, T; Furumi, K; Hatori, Y; Ikeda, Y; Ikeya, Y; Kaneda, T; Kawada, T; Kawano, T; Kawashima, T; Kihara, M; Kikuta, M; Kitamura, A; Kobayashi, H; Kobayashi, S; Kuji, T; Masuda, S; Minamimoto, Y; Minamisawa, K; Mitsuhashi, T; Miyazaki, N; Nagashima, Z; Nakatogawa, T; Nakayama, R; Nyui, N; Ogawa, M; Onishi, T; Saka, K; Sano, T; Sato, A; Shiba, K; Shionoiri, F; Sugiyama, H; Suzuki, H; Takasaki, I; Tamura, K; Tokita, Y; Umemura, M; Yamaguchi, S; Yasuda, G; Nakamura, S; Takayanagi, K; Hayashi, T; Ichihara, M; Kobayashi, S; Sakai, Y; Uchida, T; Yaguchi, I; Komuro, I; Aoki, S; Hashimoto, Y; Ibuki, C; Isobe, Y; Kumasaka, R; Matsuda, M; Mizuno, K; Murakami, D; Nakamura, S; Nakatani, M; Ohba, T; Ohara, T; Okumura, T; Saito, A; Sakurai, T; Sato, S; Sato, W; Seimiya, K; Seino, Y; Shimizu, K; Takano, M; Tokuyama, K; Uchida, D; Yodogawa, K; Oshima, S; Kurabayashi, M; Baba, N; Furushima, Y; Goto, T; Hosoi, T; Iijima, T; Ito, K; Iwata, Y; Kubo, H; Matsumoto, M; Miyazaki, M; Naganuma, F; Nakada, K; Tokushima, M; Tsunoda, K; Wakamatsu, S; Yagihara, Y; Aizawa, Y; Aizawa, M; Aizawa, M; Hayashi, N; Hori, T; Kobayashi, H; Kodama, M; Maeda, K; Miura, K; Okada, K; Okura, Y; Sasagawa, Y; Takizawa, S; Tamura, M; Yamamoto, T; Murohara, T; Awaji, Y; Funahashi, H; Hayashi, D; Iida, M; Ishihara, D; Ishikawa, S; Kamide, S; Kanashiro, M; Kurebayashi, N; Kyo, S; Matsui, H; Matsuo, K; Morishima, M; Noda, H; Noda, T; Okumura, N; Ota, T; Shimizu, S; Somura, F; Takada, Y; Takeichi, Y; Takezawa, H; Uchikawa, T; Yoshikawa, D; Kimura, G; Ando, Y; Hoshiai, M; Okuda, N; Suzuki, S; Takada, K; Takada, N; Yamada, K; Hishida, H; Furuta, T; Hayashi, H; Ito, K; Kato, K; Nomura, M; Ota, T; Ohtsuki, M; Tabata, T; Taga, S; Tateishi, R; Ito, T; Fukuda, M; Iwa, T; Wakida, Y; Yonemoto, T; Watarai, M; Ito, M; Kawai, H; Murata, Y; Nomoto, S; Takemoto, K; Tsuboi, N; Yoshida, Y; Inoue, N; Ishikawa, M; Matsumoto, M; Muramatsu, T; Yoshida, R; Ono, M; Hanaki, Y; Sano, H; Shibata, Y; Sakai, K; Ajioka, M; Asano, H; Okamoto, R; Osanai, H; Uemura, Y; Yokoi, K; Tanaka, T; Kamiya, H; Miki, K; Niwa, M; Fujiwara, H; Minatoguchi, S; Arai, T; Kato, S; Kobayashi, H; Minagawa, T; Mori, N; Nakahara, K; Shimizu, Y; Tadokoro, M; Takahashi, N; Shigemasa, T; Kobayashi, I; Nakano, T; Ito, M; Fukui, A; Higashi, Y; Ito, T; Kano, U; Makino, K; Nakai, K; Nakajima, M; Nakajima, T; Sekoguchi, K; Tanaka, T; Tanigawa, T; Takekoshi, N; Enyama, H; Hirakawa, T; Ito, J; Ito, T; Kakuda, H; Kigoshi, T; Kondo, K; Masuya, K; Matoba, M; Nakagawa, A; Nakahashi, T; Nakato, H; Okada, H; Okuro, M; Takeuchi, Y; Tsugawa, H; Urata, T; Yasuhara, M; Shimizu, M; Ino, H; Araki, T; Fujino, N; Haraki, T; Hayashi, K; Hifumi, S; Konno, T; Minamoto, M; Miyamoto, S; Mori, M; Nakanishi, C; Sakamoto, Y; Sakata, K; Takeda, S; Ueda, K; Uchiyama, K; Takata, S; Kaneko, S; Aburadani, I; Inoki, I; Kitano, K; Kobayashi, D; Kontani, K; Maekawa, M; Maruyama, M; Matsunuma, K; Nagai, Y; Nagata, Y; Okajima, M; Otowa, K; Sekiguchi, Y; Shinmura, K; Usui, S; Yokoyama, H; Yonejima, M; Nakao, K; Hiraiwa, N; Ko, T; Masuda, I; Nagae, T; Nishino, K; Sakamoto, M; Kita, T; Nakagawa, Y; Kimura, T; Doi, T; Horiuchi, H; Kinoshita, M; Mizuno, M; Ohnishi, M; Shigemoto, K; Wada, A; Yamada, T; Yoshida, H; Nakagawa, M; Matsubara, H; Furukawa, K; Hatta, T; Inoue, A; Katsume, H; Masui, A; Matsumoto, S; Seki, T; Takeda, K; Taniguchi, Y; Tsuji, H; Saito, Y; Fukuoka, Y; Iwano, M; Katsuyama, T; Nakatani, A; Sakaguchi, Y; Konishi, T; Izumi, T; Toda, I; Kamimoto, A; Nagai, Y; Matsuwaka, E; Matsuwaka, R; Takei, K; Ueda, R; Wakaki, N; Iwasaka, T; Hamada, H; Hamada, S; Koga, H; Koito, H; Kono, K; Kurihara, H; Maeda, J; Morimoto, S; Takayama, Y; Aoyama, T; Imai, M; Ii, T; Kashii, S; Maenaka, M; Ohashi, H; Suyama, T; Matsuda, M; Aoyagi, Y; Kunisada, K; Mori, T; Mori, T; Uemura, J; Yokoi, Y; Morioka, N; Ozaki, T; Kanamasa, K; Ishikawa, K; Miyazaki, S; Arima, S; Kai, T; Kurooka, A; Shimada, I; Takewa, M; Taniguchi, M; Hattori, R; Haba, K; Yokota, R; Matsui, H; Tone, E; Yamahira, H; Kawarabayashi, T; Inaba, H; Sakaguchi, Y; Yamamoto, Y; Ito, H; Date, M; Dodo, M; Fujii, K; Imai, M; Inoue, K; Kanoh, Y; Komura, N; Senpuku, S; Takeda, M; Tateyama, H; Yasui, K; Yoneda, R; Morita, H; Kawanami, M; Tahara, A; Sado, T; Takamura, T; Taniwa, M; Kitaura, Y; Fukuda, M; Hanada, H; Nakamura, K; Sawada, K; Yamaguchi, M; Kodama, K; Higo, T; Hirata, A; Kanzaki, M; Komatsu, S; Matsuo, K; Murakawa, T; Nakanishi, H; Nemoto, T; Nishio, M; Ogasawara, N; Okuyama, Y; Ueda, Y; Imanishi, M; Kitamura, Y; Sakakibara, T; Yoshida, H; Yoshimi, H; Ogihara, T; Rakugi, H; Akiyama, M; Ikuno, Y; Imai, N; Imamura, Y; Inoyama, T; Kamide, K; Katahira, K; Katsuya, S; Katsuya, T; Kurokawa, Y; Matsuki, O; Matsuo, M; Nakamura, T; Ogura, E; Ohishi, M; Sasaki, R; Sugimoto, K; Tachi, J; Tanaka, H; Tanaka, H; Tsunetoshi, T; Yoshino, M; Hori, M; Awata, N; Fukukawa, T; Iimori, Y; Iwamoto, S; Sawami, K; Okamura, M; Kanayama, Y; Nagano, F; Nakayama, H; Suzuki, H; Amano, T; Tachibana, K; Arita, Y; Kirino, M; Sakuyama, K; Shukawa, M; Nishida, Y; Sakamoto, T; Yanagi, S; Hirota, K; Majima, T; Ota, T; Tanaka, T; Nohara, R; Funauchi, T; Isogai, O; Takashima, S; Koike, H; Nishimoto, M; Kawase, Y; Tojo, O; Chimori, Y; Harada, H; Takeoka, H; Kishi, S; Yokoyama, M; Hirata, K; Ejiri, J; Emoto, R; Furuta, Y; Hattori, K; Kuroda, R; Maehashi, N; Monnaka, H; Ohashi, Y; Okada, T; Suzuki, H; Takeuchi, M; Ohyanagi, M; Masai, M; Masuyama, T; Kawabata, M; Kajiya, T; Daito, N; Fujisawa, T; Fujita, S; Hasegawa, M; Hirakoba, M; Hirano, T; Ikeda, Y; Imai, N; Marumoto, K; Masuda, S; Miki, T; Mitsunaga, M; Mitsuoka, H; Miyachi, Y; Mukohara, N; Nagao, T; Nakada, K; Nishian, K; Nishioka, S; Ogura, T; Onishi, Y; Sakaguchi, K; Sano, I; Sano, W; Shigenobu, M; Tabuchi, A; Takashima, J; Taniguchi, Y; Uchida, H; Ueda, T; Urabe, N; Makino, H; Harada, S; Hirakawa, S; Hirata, H; Ishii, J; Koten, K; Nagake, Y; Nakajima, T; Nakamura, Y; Terami, T; Mitsudo, K; Fujii, M; Fujita, K; Iwano, E; Kadota, K; Nishihara, Y; Takaya, Y; Yamamoto, H; Yamamoto, T; Shigemasa, C; Hisatome, I; Kato, T; Miyakoda, H; Sakamoto, M; Shimoyama, M; Shimada, T; Tanabe, K; Goto, Y; Hanada, Y; Kawakami, K; Kitamura, J; Kitamura, K; Nakata, H; Oyake, N; Sugiura, H; Tsukihashi, H; Matsuzaki, M; Umemoto, S; Aoyagi, S; Aoyama, H; Fujino, T; Fukuta, S; Hiroyama, N; Ikeda, Y; Inamoto, Y; Kametani, R; Kamiya, A; Kanamaru, Y; Kotoku, S; Matsushima, A; Morita, J; Murano, Y; Nakatsuka, M; Nishimura, S; Nisnimura, Y; Okamura, T; Okuda, F; Onaka, U; Ozaki, M; Shimizu, A; Takata, C; Tamitani, M; Watada, T; Watada, T; Yamamoto, K; Yamauchi, M; Yorozu, T; Yoshikane, H; Yoshino, F; Higaki, J; Doiuchi, J; Fukuoka, T; Hashimoto, H; Igase, M; Kadota, H; Kaneko, H; Komatsu, S; Matsubara, Y; Miyoshi, K; Murakami, K; Murao, S; Niiya, T; Ochi, T; Satoh, A; Seki, T; Takahashi, H; Yamashita, T; Yoshino, T; Kohno, M; Fujita, N; Fukui, T; Hamamoto, T; Hasegawa, K; Hitomi, H; Ihara, K; Kiyomoto, H; Masugata, H; Matsumoto, I; Takahashi, N; Yoshikawa, K; Doi, Y; Arisawa, M; Egawa, T; Fukuda, M; Kawada, Y; Kusunose, H; Maeda, T; Minami, N; Nishinaga, M; Noguchi, T; Okabayashi, K; Sato, K; Satomi, T; Takada, J; Tamura, S; Usui, T; Yamada, M; Irahara, M; Azuma, H; Fujimura, M; Fujino, H; Fujino, M; Harada, E; Harada, S; Hiasa, Y; Hosokawa, S; Kawahara, K; Koshiba, K; Murakami, M; Nakaya, Y; Nii, H; Nozaki, S; Ota, A; Ozaki, T; Sone, K; Tsutsui, Y; Ueta, S; Nobuyoshi, M; Fujishima, Y; Hisano, K; Ikezono, H; Imawatari, R; Izumi, Y; Kanai, H; Nakamura, T; Nakamura, T; Noda, T; Ono, E; Tanaka, S; Tsuiki, T; Yanai, T; Sasaguri, T; Akimitsu, S; Dohmen, K; Fujisawa, K; Fukuyo, K; Harashima, S; Hayashi, T; Hirata, M; Hirata, Y; Ikeda, N; Ikematsu, H; Ikematsu, W; Kajiyama, W; Kawakami, Y; Kawasaki, I; Kondo, H; Kusuhara, H; Maeda, N; Miyahara, H; Motomura, A; Nakamura, K; Noguchi, T; Okinaga, T; Sato, M; Shimada, I; Shin, H; Soejima, K; Sugi, K; Taniguchi, T; Uwatoku, T; Yamaga, S; Yamaji, K; Yanagi, J; Yano, H; Saku, K; Enomoto, M; Hiratsuka, T; Imoto, K; Kamei, R; Kanaya, H; Kohara, M; Kusuda, M; Nishikawa, H; Sako, H; Imaizumi, T; Yano, K; Maemura, K; Ashizawa, N; Hazama, M; Ishida, Y; Ito, T; Kanda, M; Kimura, M; Noguchi, T; Oku, Y; Seto, S; Suzuki, S; Ogawa, H; Goto, K; Honjio, K; Horio, Y; Jinnouchi, H; Kaku, Y; Kawano, S; Kimura, T; Kiyohara, Y; Maki, A; Matsumoto, N; Misumi, K; Sakamoto, T; Sasaki, K; Sugiyama, S; Tanaka, E; Uemura, S; Tei, C; Arima, K; Daitoku, Y; Eto, H; Hashino, T; Ichinari, K; Ikeda, Y; Iriki, A; Kiyonaga, K; Kubota, K; Makise, Y; Masuzaki, S; Miyata, M; Mizoguchi, H; Niiyama, T; Samejima, Y; Yonezawa, S

    2016-01-01

    Visit-to-visit blood pressure (BP) variability is an important predictor of stroke. However, which antihypertensive drug combination is better at reducing visit-to-visit BP variability and therefore at reducing stroke incidence remains uncertain. We have previously reported that the dihydropyridine calcium channel blocker benidipine combined with a β-blocker appeared to be less beneficial in reducing the risk of stroke than a combination of benidipine and thiazide. Here, we further compare the visit-to-visit BP variability among three benidipine-based regimens, namely angiotensin receptor blocker (ARB), β-blocker and thiazide combinations. The present post hoc analysis included 2983 patients without cardiovascular events or death during the first 18 months after randomization. We compared the BP variability (defined as the s.d. and the coefficient of variation (CV)), maximum systolic BP (SBP) and diastolic BP (DBP) of the clinic mean on-treatment BPs obtained at 6-month intervals, starting 6 months after the treatment initiation, among the 3 treatments (ARB, n=1026; β-blocker, n=966; thiazide, n=991). During the first 6–36 months after randomization, both the s.d. and CV-BPs were lower in the benidipine–thiazide group than in the benidipine–β-blocker group (s.d.-SBP, P=0.019; s.d.-DBP, P=0.030; CV-SBP, P=0.012; CV-DBP, P=0.022). The s.d. and CV in the ARB group did not reach statistical significance compared with the other two groups. The maximum BPs did not differ among the three treatments. These findings suggest that the benidipine–thiazide combination may reduce visit-to-visit BP variability more than the benidipine–β-blocker combination. PMID:26490089

  6. Effect of beta-adrenoceptor blockers on human ether-a-go-go-related gene (HERG) potassium channels

    DEFF Research Database (Denmark)

    Dupuis, Delphine S; Klaerke, Dan A; Olesen, Søren-Peter

    2005-01-01

    Patients with congenital long QT syndrome may develop arrhythmias under conditions of increased sympathetic tone. We have addressed whether some of the beta-adrenoceptor blockers commonly used to prevent the development of these arrhythmias could per se block the cardiac HERG (Human Ether....... These data showed that HERG blockade by beta-adrenoceptor blockers occurred only at high micromolar concentrations, which are significantly above the recently established safe margin of 100 (Redfern et al., 2003).......-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) blocked the HERG channel with similar affinity, whereas the beta1-receptor antagonists metoprolol and atenolol showed weak effects. Further, the four compounds blocked HERG channels expressed in a mammalian HEK293 cell line...

  7. Pro-survival function of MEF2 in cardiomyocytes is enhanced by β-blockers

    Science.gov (United States)

    Hashemi, S; Salma, J; Wales, S; McDermott, JC

    2015-01-01

    β1-Adrenergic receptor (β1-AR) stimulation increases apoptosis in cardiomyocytes through activation of cAMP/protein kinase A (PKA) signaling. The myocyte enhancer factor 2 (MEF2) proteins function as important regulators of myocardial gene expression. Previously, we reported that PKA signaling directly represses MEF2 activity. We determined whether (a) MEF2 has a pro-survival function in cardiomyocytes, and (b) whether β-adrenergic/PKA signaling modulates MEF2 function in cardiomyocytes. Initially, we observed that siRNA-mediated gene silencing of MEF2 induces cardiomyocyte apoptosis as indicated by flow cytometry. β1-AR activation by isoproterenol represses MEF2 activity and promotes apoptosis in cultured neonatal cardiomyocytes. Importantly, β1-AR mediated apoptosis was abrogated in cardiomyocytes expressing a PKA-resistant form of MEF2D (S121/190A). We also observed that a β1-blocker, Atenolol, antagonizes isoproterenol-induced apoptosis while concomitantly enhancing MEF2 transcriptional activity. β-AR stimulation modulated MEF2 cellular localization in cardiomyocytes and this effect was reversed by β-blocker treatment. Furthermore, Kruppel-like factor 6, a MEF2 target gene in the heart, functions as a downstream pro-survival factor in cardiomyocytes. Collectively, these data indicate that (a) MEF2 has an important pro-survival role in cardiomyocytes, and (b) β-adrenergic signaling antagonizes the pro-survival function of MEF2 in cardiomyocytes and β-blockers promote it. These observations have important clinical implications that may contribute to novel strategies for preventing cardiomyocyte apoptosis associated with heart pathology. PMID:27551452

  8. Pharmacodynamics of beta-blockers in heart failure: lessons from the carvedilol or metoprolol European trial.

    Science.gov (United States)

    Bauman, Jerry L; Talbert, Robert L

    2004-06-01

    Heart failure is a growing public health problem in the United States, and the approach to the treatment of heart failure has undergone a radical transformation in the past decade. The use of beta-blocker therapy in heart failure patients is now widely recommended, based on evidence from large-scale clinical trials demonstrating that bisoprolol, carvedilol, and extended-release metoprolol succinate significantly reduce morbidity and mortality in patients with heart failure. Although these agents appear to provide similar benefits, the question remains whether pharmacologic differences among them could translate to differences in clinical outcomes. The Carvedilol Or Metoprolol European Trial (COMET) compared nonselective blockade of the beta1-/beta2-/alpha1-adrenergic receptors with carvedilol versus selective beta1-blockade with immediate-release metoprolol tartrate in patients with chronic heart failure. The trial found that carvedilol significantly reduced all-cause mortality compared with immediate-release metoprolol tartrate, although there were no differences in hospitalizations. Herein we review the pharmacokinetics and pharmacodynamics of metoprolol and carvedilol. In doing so, several issues regarding the design of COMET are identified that could alter the interpretation of the results of this trial. These include the choice of dose and dosage regimen of immediate-release metoprolol tartrate, a dosage form that has never been shown to reduce mortality in patients with heart failure. Additional studies are needed to fully understand whether there are any advantages of selective versus nonselective adrenergic blockade and whether there are any clinically meaningful differences in effectiveness between beta-blockers with proven benefit in the management of chronic heart failure. The results of COMET demonstrate that all beta-blockers and dosage forms are not interchangeable when prescribed for heart failure. Clinicians should choose only those agents (and

  9. Are hERG channel blockers also phospholipidosis inducers?

    Science.gov (United States)

    Sun, Hongmao; Xia, Menghang; Shahane, Sampada A; Jadhav, Ajit; Austin, Christopher P; Huang, Ruili

    2013-08-15

    Both pharmacophore models of the human ether-à-go-go-related gene (hERG) channel blockers and phospholipidosis (PLD) inducers contain a hydrophobic moiety and a hydrophilic motif/positively charged center, so it is interesting to investigate the overlap between the ligand chemical spaces of both targets. We have assayed over 4000 non-redundant drug-like compounds for both their hERG inhibitory activity and PLD inducing potential in a quantitative high throughput screening (qHTS) format. Seventy-seven percent of PLD inducing compounds identified from the screening were also found to be hERG channel blockers, and 96.9% of the dually active compounds were positively charged. Among the 48 compounds that induced PLD without inhibiting hERG channel, 24 compounds (50.0%) carried steroidal structures. According to our results, hERG channel blockers and PLD inducers share a large chemical space. In addition, a positively charged hERG channel blocker will most likely induce PLD, while a steroid PLD inducer is less likely a hERG channel blocker. Published by Elsevier Ltd.

  10. Use of beta-blockers and risk of serious upper gastrointestinal bleeding

    DEFF Research Database (Denmark)

    Reilev, Mette; Damkier, Per; Rasmussen, Lotte

    2017-01-01

    Background: Some studies indicate a reduced risk of serious upper gastrointestinal bleeding (UGIB) for users of beta-blockers, but the association remains to be confirmed in larger studies and characterized with respect to differences among beta-blockers. We aimed to assess whether beta-blocker use...... and adjusted odds ratios (ORs) of the association between current beta-blocker use and the risk of UGIB by using conditional logistic regression and further stratified by selective and non-selective beta-blockers, respectively. Results: We identified 3571 UGIB cases and 35,582 controls. Use of beta-blockers...... was not found to be associated with a decreased risk of UGIB (adjusted OR 1.10; 95% CI: 1.00-1.21). The association remained neutral after stratification by selective and non-selective beta-blockers, and by single beta-blocker substances. Similarly, we found no association between current beta-blocker use...

  11. Resource Utilization Among Glaucoma Patients in the UK Treated with Beta-Blocker and Non-Beta-Blocker Adjunctive Therapy: A Retrospective Cohort Analysis.

    Science.gov (United States)

    Viswanathan, Ananth; Spera, Claudio; Mullins, Anmol; Covert, David; Banhazi, Judit; McDwyer, Paul; Hudson, Eibhlin; Ferreira, Alberto

    2017-07-01

    Few studies have examined outcomes and potential complications among glaucoma patients who are prescribed topical beta-blockers. This study examined resource usage (number of GP visits and hospitalizations) and diagnoses of respiratory or cardiovascular conditions among glaucoma patients prescribed beta-blockers compared to patients not prescribed beta-blockers. A retrospective cohort analysis was conducted using data from the UK Clinical Practice Research Datalink (CPRD) database over the period January 1, 2006 to March 31, 2014. Adult patients with at least one diagnosis of glaucoma were categorized into beta-blocker users and non-beta-blocker users. Beta-blocker users were further separated into patients that maintained beta-blocker therapy and patients that discontinued beta-blocker treatment in year 2 of the post-index period. The CPRD data was queried directly to obtain the number of GP visits, and hospitalizations were extracted by linking the CPRD and Hospital Episode Statistics (HES) patient-level data. In the 12 months after being prescribed beta-blockers, patients that later discontinued beta-blocker treatment had a significantly higher average number of hospitalizations than patients that maintained beta-blocker therapy and the non-beta-blocker users (p beta-blocker initiation, there was a statistically significant within-group difference pre- and post-beta-blocker initiation for all groups, but the greatest number of GP visits occurred in the patients that subsequently discontinued beta-blocker treatment (mean 19.27). Patients that discontinued beta-blocker treatment were significantly more likely to have cardiovascular events than non-beta-blocker users in the post-index period (p beta-blockers in a certain group of patients who later discontinue their use is associated with increased use of medical resources (higher number of GP visits and hospitalizations) in glaucoma patients in the UK, which may be indicative of a potential relationship between

  12. Perioperative beta-blocker use and survival in lung cancer patients.

    Science.gov (United States)

    Cata, Juan P; Villarreal, John; Keerty, Dinesh; Thakar, Dilip R; Liu, Diane D; Sood, Anil K; Gottumukkala, Vijaya

    2014-03-01

    To assess the effect of perioperative beta blockers on recurrence and overall survival after non-small cell lung cancer surgery. Retrospective study. Academic medical center. The medical records of patients with stage 1, 2, and 3a non-small cell lung cancer were divided into three different groups: those patients who never received beta blockers perioperatively, those receiving nonselective beta blockers within 60 days of surgery, and those taking selective beta blockers within 60 days of surgery. Recurrence-free survival and overall survival were the main clinical endpoints. Univariate log-rank tests and multivariate Cox proportional hazards models were used to assess the effects of selective beta blockers, nonselective beta blockers, or no beta blockers on recurrence-free survival and overall survival. The analysis included records of 435 patients. Univariate analyses showed that the use of both selective and nonselective beta blockers was associated with decreased recurrence-free survival (P = 0.014) and overall survival (P = 0.009). However, these findings were not sustained after adjusting for possible confounding variables in the multivariate analysis. The hazard ratios for recurrence-free survival (selective beta blockers vs no beta blocker use were: 1.304; 95% confidence intervals [CI] 0.973 - 1.747; P = 0.075; for nonselective beta blockers vs no beta blockers: 0.989; 95% CI 0.639 - 1.532; P = 0.962. The hazard ratios for overall survival were: selective beta blocker use vs no beta blockers: 1.335; 95% CI 0.966 - 1.846; P = 0.080; nonselective beta blocker use vs no beta blocker use: 1.108; 95% CI 0.678 - 1.812; P = 0.682. Administration of beta blockers during the perioperative period did not improve recurrence-free or overall survival in patients undergoing resection of non-small cell lung cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Long-term prescription of beta-blocker delays the progression of heart failure with preserved ejection fraction in patients with hypertension: A retrospective observational cohort study.

    Science.gov (United States)

    Gu, Jun; Fan, Yu-Qi; Bian, Ling; Zhang, Hui-Li; Xu, Zuo-Jun; Zhang, Yang; Chen, Qi-Zhi; Yin, Zhao-Fang; Xie, Yu-Shui; Wang, Chang-Qian

    2016-09-01

    Hypertension complicated with left ventricular hypertrophy (LVH) and diastolic dysfunction is one of the most common risks for heart failure with preserved ejection fraction (HFpEF). This study was designed to evaluate the influences of long-term beta-blocker prescription in these patients. This retrospective analysis included eligible patients diagnosed with hypertension, LVH (left ventricular (LV) mass index >125 g/m(2) for men and >110 g/m(2) for women) and suspected diastolic dysfunction (E/E' ratio between 8 and 15) and without clinical signs or symptoms of heart failure in our hospital medical record database (January 2005-December 2009). A total of eligible 1498 patients were enrolled, of whom 803 received beta-blocker prescription and 695 accepted non-beta-blocker therapy. With a median follow-up of 7.2 years, the new-onset symptomatic HFpEF occurred in 48 of 803 patients in the beta-blocker group (6.0%) and 92 of 695 patients in the non-beta-blocker group (13.2%, p < 0.001). Beta-blockers also generated more prominent improvement in diastolic function and LVH. And Cox proportional hazards model revealed that beta-blocker (hazard ratio (HR) 0.327, 95% confidence interval (CI): 0.121-0.540, p = 0.009) or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) exposure (HR 0.422, 95% CI: 0.210-0.699, p = 0.015) was associated with a reduced risk of new onset of symptomatic HFpEF, and the elevation of LVMI (HR 1.210, 95% CI: 1.069-1.362, p = 0.040) or E/E' (HR 1.398, 95% CI: 1.306-1.541, p = 0.032) was associated with a high risk of new onset of symptomatic HFpEF. Long-term beta-blocker exposure was associated with protective effects in terms of the incidence of new-onset symptomatic HFpEF, LV diastolic dysfunction and LVH, which might be beneficial for the delay of HFpEF progression. © The European Society of Cardiology 2016.

  14. The role of adrenergic receptors in nicotine-induced hyperglycemia ...

    African Journals Online (AJOL)

    The role of adrenergic receptors in nicotine-induced hyperglycaemia has not been well studied in amphibians. Thus, this study investigates the effects of alpha and beta adrenergic receptor blockers in nicotine-induced hyperglycaemia in the common African toad Bufo regularis. Toads fasted for 24 h were anaesthetized with ...

  15. Fluorescent β-Blockers as Tools to Study Presynaptic Mechanisms of Neurosecretion

    Directory of Open Access Journals (Sweden)

    Jose D. Machado

    2011-04-01

    Full Text Available Several, if not all adrenergic β-blockers (β-Bs, accumulate progressively inside secretory vesicles in a time- and concentration-dependent manner, and could be considered to be false neurotransmitters. This transmitter effect is most likely unrelated to their ability to block adrenergic receptors, but it could explain the delay in lowering arterial pressure in hypertensive patients. We have developed a new drug to monitor the accumulation of β-Bs inside living cells, RCTM-3, which fluoresces in the visible spectrum. Here we describe the procedure to synthesize this new compound, as well as its fluorescent properties, pharmacological profile and its accumulation inside the secretory vesicles of PC12 cells.

  16. EphA4 blockers promote axonal regeneration and functional recovery following spinal cord injury in mice.

    Directory of Open Access Journals (Sweden)

    Yona Goldshmit

    Full Text Available Upregulation and activation of developmental axon guidance molecules, such as semaphorins and members of the Eph receptor tyrosine kinase family and their ligands, the ephrins, play a role in the inhibition of axonal regeneration following injury to the central nervous system. Previously we have demonstrated in a knockout model that axonal regeneration following spinal cord injury is promoted in the absence of the axon guidance protein EphA4. Antagonism of EphA4 was therefore proposed as a potential therapy to promote recovery from spinal cord injury. To further assess this potential, two soluble recombinant blockers of EphA4, unclustered ephrin-A5-Fc and EphA4-Fc, were examined for their ability to promote axonal regeneration and to improve functional outcome following spinal cord hemisection in wildtype mice. A 2-week administration of either of these blockers following spinal cord injury was sufficient to promote substantial axonal regeneration and functional recovery by 5 weeks following injury. Both inhibitors produced a moderate reduction in astrocytic gliosis, indicating that much of the effect of the blockers may be due to promotion of axon growth. These studies provide definitive evidence that soluble inhibitors of EphA4 function offer considerable therapeutic potential for the treatment of spinal cord injury and may have broader potential for the treatment of other central nervous system injuries.

  17. Effect of nipradilol, a beta-adrenergic blocker with vasodilating activity, on oxotremorine-induced tremor in mice.

    Science.gov (United States)

    Iwata, S; Nomoto, M; Fukuda, T

    1996-10-01

    The effect of nipradilol, a nonselective beta-adrenergic receptor blocker with nitroglycerin-like vasodilating activity, on oxotremorine-induced tremor was studied in mice. General tremor in mice was elicited by 0.5 mg/kg oxotremorine. The tremor was quantified using a capacitance transducer, then analyzed by a signal processor. The strength of the tremor was expressed in "points". The point values of the tremor (mean +/- SE) in control mice for 5 mg/kg (+/-)-propranolol, 2.5 mg/kg arotinolol, 0.5 mg/kg nipradilol, 1.0 mg/kg nipradilol and 2.5 mg/kg nipradilol were 87 +/- 16, 42 +/- 6, 38 +/- 6, 99 +/- 28, 28 +/- 6 and 31 +/- 7, respectively. The strength of the tremor was reduced by all beta-blockers. Although 1.0 mg/kg nipradilol significantly reduced the tremor, further inhibition of the tremor was not obtained with dosages up to 2.5 mg/kg of the drug. In conclusion, nipradilol was effective for suppressing oxotremorine-induced tremor, as were other beta-blockers.

  18. 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

  19. [Obtaining antibodies to 1,4-dihydropyridine calcium channel blockers].

    Science.gov (United States)

    Burkin, A A; Murkin, M A

    2008-01-01

    Immunization of rabbits with amlodipine conjugated with horseradish peroxidase resulted in raising polyclonal antibodies that allowed group determination of 1,4-dihydropyridine calcium channel blockers in aqueous solutions by ELISA with a sensitivity of 0.1 to 1.0 ng/ml for amlodipine, felodipine, nifedipine, and isradipine.

  20. Cellular Responses to Beta Blocker Exposures in Marine Bivalves

    Science.gov (United States)

    β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent activation of adenylate cyclase and increases in blood pressure by limiting cAMP production and protein kinase A activation. After being taken therapeutically, β b...

  1. 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?

  2. 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...

  3. 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 ...

  4. 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 wer...

  5. 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 ...

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

    African Journals Online (AJOL)

    As a result, the role of the physicochemical properties of beta-blockers can only be determined in the simpler setting of myocardial infarction. Therefore, we conducted a restricted systematic review to evaluate the effect of initiating atenolol and metoprolol on the prevention of ventricular fibrillation following acute myocardial ...

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

    African Journals Online (AJOL)

    Adele

    management of hypertension and post myocardial infarction.4-6. Are lipophilic beta-blockers preferable for peri-operative cardioprotection? Implications from a limited systematic review of the efficacy of atenolol and metoprolol in preventing in-hospital ventricular fibrillation following acute myocardial infarction.

  8. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial.

    Science.gov (United States)

    Connolly, Stuart J; Dorian, Paul; Roberts, Robin S; Gent, Michael; Bailin, Steven; Fain, Eric S; Thorpe, Kevin; Champagne, Jean; Talajic, Mario; Coutu, Benoit; Gronefeld, Gerian C; Hohnloser, Stefan H

    2006-01-11

    Implantable cardioverter defibrillator (ICD) therapy is effective but is associated with high-voltage shocks that are painful. To determine whether amiodarone plus beta-blocker or sotalol are better than beta-blocker alone for prevention of ICD shocks. A randomized controlled trial with blinded adjudication of events of 412 patients from 39 outpatient ICD clinical centers located in Canada, Germany, United States, England, Sweden, and Austria, conducted from January 13, 2001, to September 28, 2004. Patients were eligible if they had received an ICD within 21 days for inducible or spontaneously occurring ventricular tachycardia or fibrillation. Patients were randomized to treatment for 1 year with amiodarone plus beta-blocker, sotalol alone, or beta-blocker alone. Primary outcome was ICD shock for any reason. Shocks occurred in 41 patients (38.5%) assigned to beta-blocker alone, 26 (24.3%) assigned to sotalol, and 12 (10.3%) assigned to amiodarone plus beta-blocker. A reduction in the risk of shock was observed with use of either amiodarone plus beta-blocker or sotalol vs beta-blocker alone (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.28-0.68; PAmiodarone plus beta-blocker significantly reduced the risk of shock compared with beta-blocker alone (HR, 0.27; 95% CI, 0.14-0.52; Pamiodarone, 23.5% for sotalol, and 5.3% for beta-blocker alone. Adverse pulmonary and thyroid events and symptomatic bradycardia were more common among patients randomized to amiodarone. Despite use of advanced ICD technology and treatment with a beta-blocker, shocks occur commonly in the first year after ICD implant. Amiodarone plus beta-blocker is effective for preventing these shocks and is more effective than sotalol but has an increased risk of drug-related adverse effects.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00257959.

  9. BETA-BLOCKERS IN THE TREATMENT OF ARTERIAL HYPERTENSION: EVIDENCE BASED DATA AND REAL PRACTICE

    Directory of Open Access Journals (Sweden)

    M. V. Leonova

    2015-12-01

    Full Text Available Data of the largest meta-analyzes of beta-blockers use in arterial hypertension is presented. The role of beta-blockers among other basic groups of antihypertensive drugs (thiazide diuretics, calcium channel blockers, ACE inhibitors is evaluated. Special considerations of beta-blockers use in hypertensive patients with diabetes mellitus and chronic heart failure are discussed. Special attention is paid to bisoprolol.

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

    Science.gov (United States)

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

    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 8.9h(-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. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Use of digoxin, diuretics, beta blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers in older patients in an academic hospital-based geriatrics practice.

    Science.gov (United States)

    Fishkind, D; Paris, B E; Aronow, W S

    1997-07-01

    To investigate the prevalence of and indications for digoxin use and the prevalence of beta blocker and calcium channel blocker use in older patients with previous myocardial infarction or coronary artery disease (CAD), and the prevalence of use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers in older patients with hypertension in an academic hospital-based geriatrics practice. A retrospective analysis of charts from 528 unselected older patients, seen from June 1995 through July 1996 at an academic hospital-based geriatrics practice, was performed to investigate the prevalence of digoxin use and indications for digoxin use, the prevalence of beta blocker and calcium channel blocker use in older patients with previous myocardial infarction or coronary artery disease (CAD), and the prevalence of use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers in older patients with hypertension. An academic hospital-based, primary care geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians. A total of 416 women and 112 men, mean age 81 +/- 8 years (range 58 to 101), were included in the study. Ninety-two of the 528 patients (17%) were taking digoxin. Recorded indications for digoxin were atrial fibrillation with or without congestive heart failure (CHF) in 39% of patients, CHF with sinus rhythm and abnormal left ventricular ejection fraction (LVEF) in 18% of patients, a clinical assessment of CHF with sinus rhythm and no recorded measurement of LVEF in 20% of patients, paroxysmal atrial fibrillation in 14% of patients, and coronary artery disease (CAD) in 9% of patients. Of 121 patients with previous myocardial infarction, 23 (19%) were prescribed beta blockers, and 54 (45%) were taking calcium channel blockers. Of 173 patients with CAD, 41 (24%) were treated with beta blockers, and 79 (46%) were taking calcium

  12. 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

  13. Beta blocker therapy is associated with reduced depressive symptoms 12 months post percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Battes, Linda C; Pedersen, Susanne S.; Oemrawsingh, Rohit M

    2012-01-01

    Beta blocker therapy may induce depressive symptoms, although current evidence is conflicting. We examined the association between beta blocker therapy and depressive symptoms in percutaneous coronary intervention (PCI) patients and the extent to which there is a dose-response relationship between...... beta blocker dose and depressive symptoms....

  14. The cardioprotective role of beta-blockers in patients with diabetes mellitus.

    Science.gov (United States)

    Landray, M J; Toescu, V; Kendall, M J

    2002-08-01

    This paper reviews the role of beta-blockers in the prevention of cardiovascular morbidity and mortality in patients with diabetes mellitus. There is good evidence from randomized controlled trials that beta-blockers, in particular the lipophilic agents, substantially reduce cardiovascular mortality and morbidity. However, hitherto beta-blockers have been underused in diabetic patients, perhaps because of perceived risks of beta-blocker therapy. Reappraisal of the evidence suggests that the traditional reluctance to use beta-blockers in this group is based on fears of adverse effects that are largely unfounded.

  15. Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: a prospective European study.

    Science.gov (United States)

    Ouwerkerk, W; Voors, A A; Anker, S D; Cleland, J G; Dickstein, K; Filippatos, G; van der Harst, P; Hillege, H L; Lang, C C; Ter Maaten, J M; Ng, L L; Ponikowski, P; Samani, N J; van Veldhuisen, D J; Zannad, F; Metra, M; Zwinderman, A H

    2017-06-21

    Despite clear guidelines recommendations, most patients with heart failure and reduced ejection-fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers. BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50-99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43-2.01; for beta-blocker: HR 1.70; 95% CI 1.36-2.05). Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%.

  16. Beta-blockers in cirrhosis and refractory ascites

    DEFF Research Database (Denmark)

    Kimer, Nina; Feineis, Martin; Møller, Søren

    2015-01-01

    OBJECTIVE: It is currently discussed if beta-blockers exert harmful effects and increase mortality in patients with cirrhosis and refractory ascites. In this study, we provide an overview of the available literature in this field in combination with a retrospective analysis of 61 patients...... 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...

  17. 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.

  18. 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.

  19. Stability of high-dose insulin in normal saline bags for treatment of calcium channel blocker and beta blocker overdose.

    Science.gov (United States)

    Laskey, Dayne; Vadlapatla, Rajesh; Hart, Katherine

    2016-11-01

    High-dose insulin has become a first-line therapy for treating severe calcium channel blocker and beta blocker toxicity. Insulin infusions used to treat other conditions (e.g., diabetic ketoacidosis) may be used, but this may lead to pulmonary compromise due to fluid volume overload. An obvious solution would be to use a more concentrated insulin infusion; however, data describing the stability of insulin in polyvinyl chloride bags at concentrations >1 unit/mL are not readily available. To determine the stability of insulin at 16 units/mL in 0.9% saline solution. Eight-hundred units of regular insulin (8 mL from a stock vial containing 100 units/mL) were added to 42 mL of 0.9% saline solution in a polyvinyl chloride bag to make a final concentration of 16 units/mL. Two bags were stored at 4 °C (refrigerated) and two at 25 °C (room temperature). Samples were withdrawn and tested for insulin concentration periodically over 14 days. Concentrated regular insulin in a polyvinyl chloride bag remained within 90% of equilibrium concentration at all time points, indicating the 16 units/mL concentration was sufficiently stable both refrigerated and at room temperature for 14 days. Administration of high-dose insulin can cause fluid volume overload when using traditional insulin formulations. The 16 units/mL concentration allows for the treatment of a patient with severe calcium channel blocker or beta blocker toxicity for a reasonable period of time without administering excessive fluid. Insulin at a concentration of 16 units/mL is stable for 14 days, the maximum timeframe currently allowed under US Pharmacopeia rules for compounding of sterile preparations. This stability data will allow institutions to issue beyond-use dating for intravenous fluids containing concentrated insulin and used for treating beta blocker and calcium channel blocker toxicity.

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

    Science.gov (United States)

    2016-10-01

    40%.21 22 ▸ Current therapy with ocular β-blocker medications. ▸ Critical ischaemia related to peripheral arterial disease . ▸ Other diseases that are...exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol. Bhatt, SP; Connett, JE; Voelker, H...acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol Surya P Bhatt,1 John E Connett,2 Helen

  1. Influence of calcium blockers on the SPR of erythrocytes

    Science.gov (United States)

    Shynkarenko, Olena V.; Tril, Orest; Wojnarowska, Renata; Prohorenko, Sergiy; Shergii, E. M.

    2017-01-01

    One of the promising areas of research is the impact of calcium channel blockers (CB) of biological fluids. This paper shows that the CB impact on a biological fluid can be efficiently combine with the surface plasmon resonance (SPR). It is shown that the addition of CB at the SPR measurements affect the stability of membranes and acts differently on the kinetics of erythrocytes ligament in the different groups of people.

  2. Cellular Responses to Beta Blocker Exposures in Marine ...

    Science.gov (United States)

    β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent activation of adenylate cyclase and increases in blood pressure by limiting cAMP production and protein kinase A activation. After being taken therapeutically, β blockers may make their way to coastal habitats via discharge from waste water treatment plants, posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular biomarkers of β blocker exposure using two drugs, propranolol and metoprolol, in three commercially important marine bivalves -Crassostrea virginica, Mytilus edulis and Mercenaria mercenaria. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug for 24 hours. Samples were preserved for cellular biomarker assays. Elevated cellular damage and changes in enzymatic activities were noted at environmentally relevant concentrations, and M. mercenaria was found to be the most sensitive bivalve out of the three species tested. These studies enhance our understanding of the potential impacts of commonly used prescription medication on organisms in coastal ecosystems, and demonstrate that filter feeders such as marine bivalves may serve as good model organisms to examine the effects of water soluble drugs. Evaluating a suite of biomarkers

  3. Quantitative Confocal Microscopy Analysis as a Basis for Search and Study of Potassium Kv1.x Channel Blockers

    Science.gov (United States)

    Feofanov, Alexey V.; Kudryashova, Kseniya S.; Nekrasova, Oksana V.; Vassilevski, Alexander A.; Kuzmenkov, Alexey I.; Korolkova, Yuliya V.; Grishin, Eugene V.; Kirpichnikov, Mikhail P.

    Artificial KcsA-Kv1.x (x = 1, 3) receptors were recently designed by transferring the ligand-binding site from human Kv1.x voltage-gated potassium channels into corresponding domain of the bacterial KscA channel. We found that KcsA-Kv1.x receptors expressed in E. coli cells are embedded into cell membrane and bind ligands when the cells are transformed to spheroplasts. We supposed that E. coli spheroplasts with membrane-embedded KcsA-Kv1.x and fluorescently labeled ligand agitoxin-2 (R-AgTx2) can be used as elements of an advanced analytical system for search and study of Kv1-channel blockers. To realize this idea, special procedures were developed for measurement and quantitative treatment of fluorescence signals obtained from spheroplast membrane using confocal laser scanning microscopy (CLSM). The worked out analytical "mix and read" systems supported by quantitative CLSM analysis were demonstrated to be reliable alternative to radioligand and electrophysiology techniques in the search and study of selective Kv1.x channel blockers of high scientific and medical importance.

  4. Genetics of Taste Receptors

    Science.gov (United States)

    Bachmanov, Alexander A.; Bosak, Natalia P.; Lin, Cailu; Matsumoto, Ichiro; Ohmoto, Makoto; Reed, Danielle R.; Nelson, Theodore M.

    2016-01-01

    Taste receptors function as one of the interfaces between internal and external milieus. Taste receptors for sweet and umami (T1R [taste receptor, type 1]), bitter (T2R [taste receptor, type 2]), and salty (ENaC [epithelial sodium channel]) have been discovered in the recent years, but transduction mechanisms of sour taste and ENaC-independent salt taste are still poorly understood. In addition to these five main taste qualities, the taste system detects such noncanonical “tastes” as water, fat, and complex carbohydrates, but their reception mechanisms require further research. Variations in taste receptor genes between and within vertebrate species contribute to individual and species differences in taste-related behaviors. These variations are shaped by evolutionary forces and reflect species adaptations to their chemical environments and feeding ecology. Principles of drug discovery can be applied to taste receptors as targets in order to develop novel taste compounds to satisfy demand in better artificial sweeteners, enhancers of sugar and sodium taste, and blockers of bitterness of food ingredients and oral medications. PMID:23886383

  5. β-blocker prevents sudden cardiac death in patients with hemodialysis.

    Science.gov (United States)

    Matsue, Yuya; Suzuki, Makoto; Nagahori, Wataru; Ohno, Masakazu; Matsumura, Akihiko; Hashimoto, Yuji

    2013-05-25

    Beta blockers were shown to prevent SCD in cardiomyopathy or coronary artery disease patients. Dialysis patients show elevated mortality rates, predominantly due to cardiovascular disease. SCD is now one of the leading causes of death in this population. However, the prevention of SCD remains to be elucidated. We conducted a retrospective study of 316 patients from a database of all patients undergoing maintenance hemodialysis and followed up for 4.9 years. All patients were followed-up until death. Cox regression analysis was used to adjust the hazard ratio for beta blocker use with time until death. SCD occurred during the study period in 3 (3.8%) patients in the beta blocker group and in 27 (11.4%) patients in the non-beta blocker group (P=0.047). Death from all causes occurred in 15 (18.8%) patients in the beta blocker group and in 97 (41.3%) patients in the non-beta blocker group (Pbeta blocker group (log-rank test, P=0.028 and Pbeta blocker use was significantly associated with lower adjusted risk of SCD (multivariate adjusted hazard ratio, 0.201; 95% confidence interval, 0.058-0.693; P=0.011). In hemodialysis patients, beta blocker use was associated with lower risks of SCD and death from all causes. Thus, beta blocker use in this high-risk population may substantially improve outcome. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Survival and hospitalization in heart failure patients with or without diabetes treated with beta-blockers.

    Science.gov (United States)

    Bobbio, Marco; Ferrua, Stefania; Opasich, Cristina; Porcu, Maurizio; Lucci, Donata; Scherillo, Marino; Tavazzi, Luigi; Maggioni, Aldo Pietro

    2003-06-01

    Physicians are still concerned about prescribing beta-blockers in diabetic patients with heart failure. In the outcome research study (the Beta-Blockers in Patients With Congestive Heart Failure: Guided Use in Clinical Practice [BRING-UP] study), the responsible clinicians could decide whether to start beta-blocker treatment and which agent to use. A total of 3091 patients were enrolled by 202 cardiologic centers: 25% of the recruited patients were already on beta-blockers, 28% started treatment at the enrollment visit, and 47% were not started on beta-blockers. The 1-year mortality, hospitalization rate, and the combined end point of mortality or hospitalization were higher in diabetic patients (15.8% versus 10.9%; relative risk [RR] = 1.44; 95% confidence intervals [CI] 1.16-1.78, P =.001) (31.0% versus 24.0%; RR = 1.28; 95% CI 1.11-1.49; P =.0009) (40.5% versus 30.1%; RR = 1.35; 95% CI 1.19-1.51; P =.0001). The event-free analysis of the 4 groups (diabetic patients not treated with beta-blockers, diabetic patients treated with beta-blockers, nondiabetic patients not treated with beta-blockers, nondiabetic patients treated with beta-blockers) showed that patients treated with beta-blockers had a higher event-free probability than patients not treated with beta-blockers regardless the presence of diabetes (P <.0001). On the basis of post hoc analysis, diabetic patients with chronic heart failure benefit from beta-blockers even if at a lower degree. Thus, there are no justifications to avoid beta-blockers in heart failure patients in the presence of diabetes.

  7. Beta-3 adrenergic agonist, BRL-26830A, and alpha/beta blocker, arotinolol, markedly increase regional blood flow in the brown adipose tissue in anesthetized rats.

    Science.gov (United States)

    Takahashi, H; Yoshida, T; Nishimura, M; Nakanishi, T; Kondo, M; Yoshimura, M

    1992-09-01

    Regional vascular effects of some adrenergic agents, focussing on brown adipose tissue (BAT), were investigated using tracer microspheres with a reference sample method in the anesthetized rat. Intravenous injections of 0.5 mg/kg BRL-26830A, a beta 3-adrenergic agonist, increased heart rate, but changes in blood pressure and cardiac output were not significant. The drug decreased blood flow in the brain, the spleen and the kidneys, but markedly increased it in BAT. At 2 mg/kg, arotinolol, an alpha/beta-adrenergic blocker, decreased blood pressure by 20 mmHg and increased cardiac output by 95 ml/min/kg. It slightly but significantly decreased blood flow in the liver and the spleen, but markedly increased the flow in BAT. Acebutolol, a beta 1-adrenergic blocker, decreased blood flow in the liver, the spleen, the pancreas, the kidneys, the adrenals, the skeletal muscle and the skin. Bunazosin, an alpha 1-adrenergic blocker, decreased it in all organs and tissue expect the brain and BAT. The pattern of redistribution of blood flow by arotinolol was very similar to that caused by BRL-26830A. Acebutolol and bunazosin rather decreased the blood flow in the BAT. These results indicate that stimulation of beta 3-adrenergic receptors, in BAT results in vasodilation, and that arotinolol may bind to those beta 3-adrenergic receptors.

  8. 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

    INTRODUCTION: The prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy. OBJECTIVE: The objective of this study was to investigate whether first-trimester use of beta-blockers increases...... for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly......-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...

  9. Metastasis Risk Reduction Related with Beta-Blocker Treatment in Mexican Women with Breast Cancer.

    Science.gov (United States)

    Parada-Huerta, E; Alvarez-Dominguez, Tp; Uribe-Escamilla, R; Rodriguez-Joya, Jf; Ponce-Medrano, Ja Diaz; Padron-Lucio, S; Alfaro-Rodriguez, A; Bandala, C

    2016-01-01

    Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked β2-adrenergic receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel- Haenszel, Student t, and ANOVA tests were performed for data analysis. On average, patients were 54.8±11.8 years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for β1 - and β2 -adrenergic-receptors did not present metastasis globally, but patients treated with β1 BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. In Mexican patients with BCa and SAH treated with non-selective (β1- and β2-adrenergic receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.

  10. Two novel real time cell-based assays quantify beta-blocker and NSAID specific effects in effluents of municipal wastewater treatment plants.

    Science.gov (United States)

    Bernhard, Kevin; Stahl, Cordula; Martens, Regina; Köhler, Heinz-R; Triebskorn, Rita; Scheurer, Marco; Frey, Manfred

    2017-05-15

    Pharmaceuticals, such as beta-blockers, nonsteroidal anti-inflammatory drugs (NSAIDs) as well as their metabolites are introduced into the water cycle via municipal wastewater treatment plant (WWTP) effluents in all industrialized countries. As the amino acid sequences of the biological target molecules of these pharmaceuticals - the beta-1 adrenergic receptor for beta-blockers and the cyclooxygenase for NSAIDs - are phylogenetically conserved among vertebrates it is reasonable that wildlife vertebrates including fish physiologically respond in a similar way to them as documented in humans. Consequently, beta-blockers and NSAIDs both exhibit their effects according to their mode of action on one hand, but on the other hand that may lead to unwanted side effects in non-target species. To determine whether residuals of beta-1 adrenergic receptor antagonists and cyclooxygenase inhibitors may pose a risk to aquatic organisms, one has to know the extent to which such organisms respond to the total of active compounds, their metabolites and transformation products with the same modes of action. To cope with this demand, two cell-based assays were developed, by which the total beta-blocker and cyclooxygenase inhibitory activity can be assessed in a given wastewater or surface water extract in real time. The measured activity is quantified as metoprolol equivalents (MetEQ) of the lead substance metoprolol in the beta-blocker assay, and diclofenac equivalents (DicEQ) in the NSAID assay. Even though MetEQs and DicEQs were found to surpass the concentration of the respective lead substances (metoprolol, diclofenac), as determined by chemical analysis by a factor of two to three, this difference was shown to be reasonably explained by the presence and action of additional active compounds with the same mode of action in the test samples. Thus, both in vitro assays were proven to integrate effectively over beta-blocker and NSAID activities in WWTP effluents in a very sensitive

  11. AT2 Receptors Targeting Cardiac Protection Post-Myocardial Infarction

    DEFF Research Database (Denmark)

    Kaschina, Elena; Lauer, Dilyara; Schmerler, Patrick

    2014-01-01

    is preserved over periods of up to four months. Depending on the experimental protocol, the AT2R also attenuates post-MI left ventricular remodeling or protects the heart from early left ventricular thinning and rupture. In combination with AT1-receptor blockade or deficiency, post-MI cardiac hypertrophy...... deficiency or overexpression, treatment with an AT1-receptor blocker leading to indirect stimulation of the unopposed AT2-receptor, or studies using AT2-receptor agonists. It is a common finding in these studies that the AT2-receptor improves cardiac function in the early phase post-MI, and that this effect...

  12. 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......-selective beta-blockers for patients with oesophageal varices and no history of bleeding have reached equivocal results....

  13. 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.

  14. The effect of beta blocker withdrawal on adenosine myocardial perfusion imaging.

    Science.gov (United States)

    Hoffmeister, C; Preuss, R; Weise, R; Burchert, W; Lindner, O

    2014-12-01

    The effect of beta blockers on myocardial blood flow (MBF) under vasodilators has been studied in several SPECT and PET myocardial perfusion imaging (MPI) studies with divergent results. The present study evaluated the effect of a beta blocker withdrawal on quantitative adenosine MBF and on MPI results. Twenty patients with beta blockers and CAD history were studied with quantitative adenosine N-13 ammonia PET. The first study was performed under complete medication and the second after beta blocker withdrawal. The PET studies were independently read with respect to MPI result and clinical decision making. Global MBF showed an increase from 180.2 ± 59.9 to 193.6 ± 60.8 mL·minute(-1)/100 g (P = .02) after beta blocker withdrawal. The segmental perfusion values were closely correlated (R(2) = 0.82) over the entire range of perfusion values. An essentially different interpretation after beta blocker discontinuation was found in two cases (10%). A beta blocker withdrawal induces an increase in adenosine MBF. In the majority of cases, MPI interpretation and decision making are independent of beta blocker intake. If a temporary beta blocker withdrawal before MPI is not possible or was not realized by the patient, it is appropriate to perform adenosine stress testing without loss of the essential MPI result.

  15. Beta-blocker use in ST-segment elevation myocardial infarction in the reperfusion era (GRACE).

    Science.gov (United States)

    Park, Kay Lee; Goldberg, Robert J; Anderson, Frederick A; López-Sendón, José; Montalescot, Gilles; Brieger, David; Eagle, Kim A; Wyman, Allison; Gore, Joel M

    2014-06-01

    Current guidelines recommend early oral beta-blocker administration in the management of acute coronary syndromes for patients who are not at high risk of complications. Data from patients enrolled between 2000 and 2007 in the Global Registry of Acute Coronary Events (GRACE) were used to evaluate hospital outcomes in 3 cohorts of patients admitted with ST-elevation myocardial infarction, based on beta-blocker use (early [first 24 hours] intravenous (IV) [± oral], only early oral, or delayed [after first 24 hours]). Among 13,110 patients with ST-elevation myocardial infarction, 21% received any early IV beta-blockers, 65% received only early oral beta-blockers, and 14% received delayed (>24 hours) beta-blockers. Higher systolic blood pressure, higher heart rate, and chronic beta-blocker use were independent predictors of early beta-blocker use. Early beta-blocker use was less likely in older patients, patients with moderate to severe left ventricular dysfunction, and in those presenting with inferior myocardial infarction or Killip class II or III heart failure. IV beta-blocker use and delayed beta-blocker use were associated with higher rates of cardiogenic shock, sustained ventricular fibrillation/ventricular tachycardia, and acute heart failure, compared with oral beta-blocker use. In-hospital mortality was increased with IV beta-blocker use (propensity score adjusted odds ratio, 1.41; 95% confidence interval, 1.03-1.92) but significantly reduced with delayed beta-blocker administration (propensity adjusted odds ratio, 0.44; 95% confidence interval, 0.26-0.74). Early beta-blocker use is common in patients presenting with ST-elevation myocardial infarction, with oral administration being the most prevalent. Oral beta-blockers were associated with a decrease in the risk of cardiogenic shock, ventricular arrhythmias, and acute heart failure. However, the early receipt of any form of beta-blockers was associated with an increase in hospital mortality. Copyright

  16. 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.

  17. Sodium Channel Blockers in the Treatment of Epilepsy.

    Science.gov (United States)

    Brodie, Martin J

    2017-07-01

    Sodium channel blockers have been the mainstay of the pharmacological management of focal and generalised tonic-clonic seizures for more than 70 years. The focus of this paper will be on phenytoin, carbamazepine, lamotrigine, oxcarbazepine, rufinamide, lacosamide and eslicarbazepine acetate. All these antiepileptic drugs have similar efficacy and share similar dose-dependent, adverse effect profiles, although phenytoin, carbamazepine and oxcarbazepine are more likely to cause idiosyncratic reactions than the others. With the exception of lamotrigine, rufinamide and lacosamide, all are enzyme inducers and most are minor teratogens; although data on teratogenicity are sparse with lacosamide and eslicarbazepine acetate. There is increasing evidence that these drugs differ mechanistically, with the newer agents, lacosamide and eslicarbazepine acetate, having their major pharmacological effect on the slow inactivation state of the sodium channel, which may be associated with better tolerability at higher dosage, although hard evidence in support of this observation is currently not available. Rufinamide is licensed only for Lennox-Gastaut syndrome in children aged 4 years and above. There is a move away from using enzyme inducers, particularly phenytoin and carbamazepine, in everyday clinical practice. There seems little doubt, however, that some sodium channel blockers will have an enduring place in the management of epilepsy well into the 21st century.

  18. In depth pharmacological characterization of endothelin B receptors in the rat middle cerebral artery

    DEFF Research Database (Denmark)

    Szok, D; Hansen-Schwartz, J; Edvinsson, L

    2001-01-01

    endothelin B receptor agonist sarafotoxin 6c in precontracted cerebral arteries and in the presence of the endothelin A receptor blocker FR139317 caused vasodilation in a concentration-dependent manner. Inhibition of nitric oxide synthase significantly reduced the dilation induced by sarafotoxin 6c, whereas...

  19. Influence of external magnesium ions on the NMDA receptor channel block by different types of organic cations.

    Science.gov (United States)

    Nikolaev, Maxim V; Magazanik, Lev G; Tikhonov, Denis B

    2012-04-01

    The NMDA type of ionotropic glutamate receptors plays a unique role in synaptic functions because of high permeability for calcium and because of a voltage-dependent block by endogenous Mg(2+). Activity and voltage dependence of the NMDA receptor channel block by organic cations are strongly affected by competition with magnesium ions for the binding site in the channel pore. It complicates prediction of action of NMDA receptor channel blockers in vivo. In the present work we studied the NMDA receptor channel block in the presence of Mg(2+) by several organic blockers with different characteristics of voltage dependence and mechanism of action. The action of NMDA receptor channel antagonists was studied in native NMDA receptors of hippocampus CA1 pyramidal neurons isolated from rat brain slices. It was demonstrated that the IC(50) values of NMDA receptor channel blockers at -30 mV are increased 1.5-5 times compared with magnesium-free conditions. The voltage dependence of the channel block is decreased, abolished or even inversed in the presence of magnesium. Although simple competition between magnesium ion and organic channel blockers provides a general explanation of the observed effects, certain disagreements were revealed. Diversity in Mg(2+) effects on the NMDAR channel block by different organic cations reported herein likely reflects interaction of NMDAR channel blockers with additional binding site(s) and suggests that individual analysis in the presence of Mg(2+) is required for newly developed NMDAR channel blocking drugs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Is Beta-Blocker Use Beneficial in Breast Cancer? A Meta-Analysis.

    Science.gov (United States)

    Kim, Hyun Yul; Jung, Youn Joo; Lee, Sang Hyup; Jung, Hyuk Jae; Pak, Kyoungjune

    2017-01-01

    Preclinical studies have proved that beta-blocking agents inhibit several pathways for breast cancer progression and metastasis. We aimed to evaluate the association between beta-blocker use and prognosis of breast cancer. A systematic search for studies from MEDLINE and EMBASE (inception to March 2014) was performed using the keywords "breast cancer" and "beta-blocker." In 2 groups of breast cancer patients (beta-blocker users and non-beta-blocker users), overall deaths (ODs), cancer-specific deaths (CSDs), and recurrences were compared. Six studies including 18,118 patients were eligible for this analysis. Two studies with 3,139 patients were included in the analysis of ODs. The random-effects model showed no significant difference in ODs between beta-blocker users and non-beta-blocker users (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.50-1.52, p = 0.49). Four studies with 13,782 patients were included in the measurement of CSDs. The difference in CSDs between beta-blocker users and non-beta-blocker users was not significant using the fixed-effect model (OR 0.93, 95% CI 0.82-1.06, p = 0.29). Three studies with 3,923 patients were included in the calculation of recurrences. Overall, beta-blockers did not affect the incidence of recurrence (OR 0.70, 95% CI 0.25-1.95, p = 0.49). Beta-blockers were not beneficial regarding ODs, CSDs, or recurrences. Further studies are needed to evaluate the associations between the effects of beta-blockers and subtypes of breast cancer. © 2017 S. Karger AG, Basel.

  1. Beta blocker use and colorectal cancer risk: population-based case-control study.

    Science.gov (United States)

    Jansen, Lina; Below, Janina; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael

    2012-08-15

    Recently, it has been postulated that long-term use of beta blockers might decrease the risk of certain types of cancer because of weakening of norepinephrine signaling. Previous studies on colorectal cancer (CRC) yielded inconsistent results, but lacked information on covariates. Thus, the authors investigated the association of beta blocker use and CRC risk in a large population-based case-control study (DACHS study). Between 2003 and 2007, information on beta blocker use and potential confounders was collected by personal interviews for 1762 CRC cases and 1708 control individuals from Germany. The association of CRC risk and beta blocker use and subclasses of beta blockers was estimated by multiple logistic regression. In addition, site- and stage-specific analyses were performed. After adjustment for covariates, no association was observed with beta blocker use (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.86-1.29) or with duration of beta blocker use. Also, the analysis by subclasses of beta blockers (cardioselectivity) and active ingredients (metoprolol, bisoprolol, carvedilol, and atenolol) or by CRC subsite showed no associations. In stage-specific analyses, long-term beta blocker use (6+ years) was associated with a significantly higher risk of stage IV CRC (OR, 2.02; 95% CI, 1.25-3.27). Our adjusted results do not support the hypothesis that beta blocker use is associated with decreased risk of CRC. In contrast, we found a positive association of long-term beta blocker use and risk of stage IV CRC. The latter result should be further evaluated in future studies. Copyright © 2012 American Cancer Society.

  2. 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

  3. 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.

  4. Actions of Calcium Channel Blockers on Vascular Proteoglycan Synthesis: Relationship to Atherosclerosis

    Science.gov (United States)

    Survase, Soniya; Ivey, Melanie E; Nigro, Julie; Osman, Narin; Little, Peter J

    2005-01-01

    Calcium channel blockers (CCBs) are a widely used group of antihypertensive agents. CCBs are efficacious in the reduction of blood pressure but the extent to which they manifest beneficial effects on cardiovascular disease is variable. Clinical studies indicate that pleiotropic actions make significant contributions to the efficacy of agents aimed at preventing atherosclerosis. The “response to retention” hypothesis implicates the binding and retention of lipoproteins by glycosaminoglycan chains on proteoglycans as an initiating step in atherogenesis. Atherogenic factors act as agonists and several classes of drugs including peroxisome proliferating-activated receptor (PPAR)-α and -γ ligands act as antagonists in this model. Initial data have demonstrated that high concentrations of CCBs inhibit proteoglycan synthesis. Newer preliminary data show that the action is very modest at reasonable concentrations and appears to be independent of calcium channel blocking activity. We have reviewed the role of cardiovascular drugs acting on vascular smooth muscle proteoglycan synthesis and considered the potential action of CCBs in this model. We conclude that the inhibition of proteoglycan synthesis by CCBs does not play a role in the attenuation of atherosclerosis; however, the antihypertensive efficacy and alternative beneficial actions provide support for the use of CCBs in the therapy of cardiovascular disease. PMID:17319105

  5. Castration prevents calcium channel blocker-induced gingival hyperplasia in beagle dogs.

    Science.gov (United States)

    Dayan, D; Kozlovsky, A; Tal, H; Kariv, N; Shemesh, M; Nyska, A

    1998-07-01

    1. The purpose of this study was to investigate testosterone's role on the calcium channel antagonist oxodipine-inducing gingival hyperplasia in a dog model. 2. Two experiments were conducted using castrated and intact male dogs. Oxodipine was administered orally for 90 days, at a dose of 24 mg/kg/day. In the first experiment, the occurrence of gingival hyperplasia was evaluated. In the second, the gingival index (GI) and gingival hyperplasia index (GHI) were recorded and correlated with serum levels of testosterone. 3. A significant positive correlation between GI, GHI and plasma testosterone was noted. Castrated dogs were injected with testosterone, 4 months after the start of oxodipine treatment, while in the non-castrated dogs, administration of oxodipine was stopped. Castration correlated with lack of GH, while testosterone injection to the same dogs was associated with an increase of GI and GHI. 4. Since it is known that testosterone receptors are present in the gingiva, it is proposed that oxodipine-induced gingival hyperplasia could be mediated by the calcium channel blocker on plasma testosterone levels.

  6. GPER blockers as Nox downregulators: A new drug class to target chronic non-communicable diseases.

    Science.gov (United States)

    Meyer, Matthias R; Barton, Matthias

    2018-02-01

    Oxidative stress is a hallmark of chronic non-communicable diseases such as arterial hypertension, coronary artery disease, diabetes, and chronic renal disease. Cardiovascular diseases are characterized by increased production of reactive oxygen species (ROS) by NAPDH oxidase 1 (Nox1) and additional Nox isoforms among other sources. Activation of the G protein-coupled estrogen receptor (GPER) can mediate multiple salutary effects on the cardiovascular system. However, GPER also has constitutive activity, e.g. in the absence of specific agonists, that was recently shown to promote hypertension and aging-induced tissue damage by promoting Nox1-derived production of ROS. Furthermore, the small molecule GPER blocker (GRB) G36 reduces blood pressure and vascular ROS production by selectively down-regulating Nox1 expression. These unexpected findings revealed GRBs as first in class Nox downregulators capable to selectively reduce the increased expression and activity of Nox1 in disease conditions. Here, we will discuss the paradigm shift from selective GPER activation to ligand-independent, constitutive GPER signaling as a key regulator of Nox-derived oxidative stress, and the surprising identification of GRBs as the first Nox downregulators for the treatment of chronic non-communicable diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Tailored Cyclodextrin Pore Blocker Protects Mammalian Cells from Clostridium difficile Binary Toxin CDT

    Directory of Open Access Journals (Sweden)

    Maurice Roeder

    2014-07-01

    Full Text Available Some Clostridium difficile strains produce, in addition to toxins A and B, the binary toxin Clostridium difficile transferase (CDT, which ADP-ribosylates actin and may contribute to the hypervirulence of these strains. The separate binding and translocation component CDTb mediates transport of the enzyme component CDTa into mammalian target cells. CDTb binds to its receptor on the cell surface, CDTa assembles and CDTb/CDTa complexes are internalised. In acidic endosomes, CDTb mediates the delivery of CDTa into the cytosol, most likely by forming a translocation pore in endosomal membranes. We demonstrate that a seven-fold symmetrical positively charged β-cyclodextrin derivative, per-6-S-(3-aminomethylbenzylthio-β-cyclodextrin, which was developed earlier as a potent inhibitor of the translocation pores of related binary toxins of Bacillus anthracis, Clostridium botulinum and Clostridium perfringens, protects cells from intoxication with CDT. The pore blocker did not interfere with the CDTa-catalyzed ADP-ribosylation of actin or toxin binding to Vero cells but inhibited the pH-dependent membrane translocation of CDTa into the cytosol. In conclusion, the cationic β-cyclodextrin could serve as the lead compound in a development of novel pharmacological strategies against the CDT-producing strains of C. difficile.

  8. 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...

  9. 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

  10. Beta-blockers and depression after myocardial infarction - A multicenter prospective study

    NARCIS (Netherlands)

    van Melle, Joost P.; Verbeek, Danielle E. P.; van den Berg, Maarten P.; Ormel, Johan; van der Linde, Marcel R.; de Jonge, Peter

    2006-01-01

    OBJECTIVES The purpose of this research was to explore the prospective relationship between the use of beta-blockers and depression in myocardial infarction (MI) patients. BACKGROUND Beta-blocker use has been reported to be associated with the development of depression, but the methodological

  11. [Elderly heart failure patients and the role of beta-blocker therapy

    NARCIS (Netherlands)

    Middeljans-Tijssen, C.W.; Jansen, R.W.M.M.

    2006-01-01

    In this article different aspects of chronic heart failure in old age are described. We mainly focus on the place of beta-blocker therapy in chronic heart failure. Beta-blockers are recommended for the treatment of stable chronic heart failure with left ventricular systolic dysfunction. There is

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

    NARCIS (Netherlands)

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

    2014-01-01

    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

  14. Beta blocker therapy is associated with reduced depressive symptoms 12 months post percutaneous coronary intervention

    NARCIS (Netherlands)

    Battes, L.C.; Pedersen, S.S.; Oemrawsingh, R.M.; van Geuns, R.-J.M.; Al Amri, I.; Regar, E.; de Jaegere, P.T.; Serruys, P.W.; van Domburg, R.T.

    2012-01-01

    Background Beta blocker therapy may induce depressive symptoms, although current evidence is conflicting. We examined the association between beta blocker therapy and depressive symptoms in percutaneous coronary intervention (PCI) patients and the extent to which there is a dose–response

  15. Patient attitudes towards deprescribing of alpha-blockers and willingness to participate in a discontinuation trial

    NARCIS (Netherlands)

    Edelman, M; Blanker, M.; Jellema, P.; Hak, E.; Denig, P.

    2017-01-01

    Hypothesis/aims of study Alpha-blockers are the first choice of drug treatment for male LUTS. The Dutch guideline for general practitioners (GPs) “Male LUTS” recommends to discontinue α-blockers in case of symptom relief after 12-26 weeks [1]. No evidence is given to support this advice. In

  16. Beta-blocker use and clinical outcomes after primary vascular surgery

    DEFF Research Database (Denmark)

    Høgh, A.; Lindholt, J.S.; Nielsen, Henrik

    2013-01-01

    To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction.......To explore the associations between beta-blocker use and clinical outcomes (death, hospitalisation with myocardial infarction (MI) or stroke, major amputation and recurrent vascular surgery) after primary vascular reconstruction....

  17. Renin Angiotensin System Blocker Fetopathy: A Midwest Pediatric Nephrology Consortium Report.

    Science.gov (United States)

    Nadeem, Shahid; Hashmat, Shireen; Defreitas, Marissa J; Westreich, Katherine D; Shatat, Ibrahim F; Selewski, David T; Onder, Ali M; Chiang, Myra; Weaver, Donald J; Steinke, Julia; Barcia, John; Hernandez, Joel; Hidalgo, Guillermo; Ingraham, Susan E; Abitbol, Carolyn L; Pan, Cynthia; Greenbaum, Larry A

    2015-10-01

    Fetuses continue to be exposed to renin angiotensin system (RAS) blockers despite their known teratogenicity and a black box warning. We hypothesized that fetopathy from in utero exposure to RAS blockers has a broader spectrum of clinical manifestations than described previously and that there are a variety of clinical scenarios leading to such exposures. This was a retrospective study performed through the Midwest Pediatric Nephrology Consortium. Cases of RAS blocker fetopathy were identified, with determination of renal and extrarenal manifestations, timing of exposure, and the explanation for the fetal exposure. Twenty-four cases were identified. RAS blocker exposure after the first trimester was associated with more severe renal manifestations. Chronic dialysis or kidney transplantation was required in 8 of 17 (47%) patients with RAS blocker exposure after the first trimester and 0 of 7 patients with exposure restricted to the first trimester (P = .05). Extrarenal manifestations, some not previously noted in the literature, included central nervous system anomalies (cystic encephalomalacia, cortical blindness, sensorineural hearing loss, arachnoid cysts) and pulmonary complications (pneumothorax, pneumomediastinum). RAS blocker exposure usually was secondary to absent or poor prenatal care or undiagnosed pregnancy. RAS blocker fetopathy continues to be a cause of considerable morbidity, with more severe renal manifestations associated with exposure after the first trimester. A variety of significant extrarenal manifestations occur in these patients. Clinicians should emphasize the risk of fetopathy when prescribing RAS blockers to women of childbearing age. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Heart rate is a useful marker of adherence to beta-blocker treatment in hypertension.

    Science.gov (United States)

    Kociánová, Eva; Václavík, Jan; Tomková, Jana; Ondra, Peter; Jarkovský, Jiří; Benešová, Klára; Václavík, Tomáš; Kamasová, Monika; Táborský, Miloš

    2017-10-01

    Suboptimal medication adherence is common among patients with hypertension. Measurements of plasma or urinary levels of antihypertensive drugs are useful, but not widely available. The aim of our study was to investigate the relation of patients' heart rates to their serum beta-blocker levels. We correlated 220 measurements of serum beta-blocker levels in 106 patients with apparently resistant hypertension to their corresponding office heart rate. A significant proportion, 44.6% of patients, were non-adherent to beta-blocker treatment according to serum level measurement. Non-adherent patients had significantly higher heart rates (80.9 vs. 66.6 bpm, p beta-blocker treatment with a sensitivity of 62.5%, specificity 86.8% and AUC ROC 0.802 (p beta-blocker treatment, and might become a quick and easy measure to determine patient adherence in hypertensive patients.

  19. Poor tolerance of beta-blockers by elderly patients with heart failure

    Directory of Open Access Journals (Sweden)

    Satoshi Yanagisawa

    2010-11-01

    Full Text Available Satoshi Yanagisawa, Noriyuki Suzuki, Toshikazu TanakaDepartment of Cardiology, Okazaki City Hospital, Aichi, JapanAbstract: Despite the well-understood importance of beta-blocker therapy in heart failure, it is sometimes not possible to use beta-blockers in elderly patients due to poor tolerance. In this report, we describe the case of an 83-year-old patient with severe systolic heart failure complicated by aortic valve stenosis and atrial fibrillation. A simple therapeutic approach involving discontinuation of beta-blockers remarkably alleviated the symptoms such as left ventricular ejection fraction, and improved the chest radiography and laboratory findings; further, atrial fibrillation converted to sinus rhythm. It is important to carefully administer beta-blocker therapy to elderly patients with heart failure, especially after considering cardiac output.Keywords: elderly, octogenarians, beta-blockers, heart failure

  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

    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...... 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...... 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. Use of beta-blockers for heart failure in patients with diabetes mellitus.

    Science.gov (United States)

    Giles, Thomas D

    2002-11-01

    Although strong evidence supports the use of beta-blockers for reducing morbidity and improving survival rates in patients with heart failure, this treatment is often underused. The presence of comorbidities, such as diabetes mellitus, is considered a precaution to the use of beta-blockers and may contribute to this underutilization. Recently completed retrospective analyses of subgroups of patients from several large, landmark heart failure trials, such as Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF), Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), and the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, have established the beneficial effects of beta-blockers in diabetic patients with heart failure. beta-blockers are as beneficial and well tolerated in patients with heart failure and diabetes as they are in those without diabetes. These observations strongly support a role for the use of beta-blockers in patients with both heart failure and diabetes.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. The renin-angiotensin system and its blockers

    Directory of Open Access Journals (Sweden)

    Igić Rajko

    2014-01-01

    Full Text Available Research on the renin-angiotensin system (RAS has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

  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...... dose change = 33.4 % [IQR 2.0-115.1]). Still, comparing final daily doses to discharge doses, 40.2 % did not change dose group (median dose change -5.7 % [IQR -18.0 to 4.2]). Only 31.5 % reached a final daily dose >50 % of target dose. CONCLUSIONS: Target dose BB treatment was infrequently achieved...... at discharge following MI. Despite dose up-titration early after discharge, most patients did not receive target dose BB treatment approximately 1 year following MI....

  6. Beta blockers and breast cancer mortality: a population- based study.

    Science.gov (United States)

    Barron, Thomas I; Connolly, Roisin M; Sharp, Linda; Bennett, Kathleen; Visvanathan, Kala

    2011-07-01

    Preclinical studies have demonstrated that antagonism of β₂-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer-specific mortality. Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (β₁/β₂ antagonist; n = 70) or atenolol (β₁ antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer-specific mortality were assessed. Propranolol users were significantly less likely to present with a T4 (odds ratio [OR], 0.24, 95% CI, 0.07 to 0.85) or N2/N3/M1 (OR, 0.20; 95% CI, 0.04 to 0.88) tumor compared with matched nonusers. The cumulative probability of breast cancer-specific mortality was significantly lower for propranolol users compared with matched nonusers (hazard ratio, 0.19; 95% CI, 0.06 to 0.60). There was no difference in T4 or N2/N3/M1 tumor incidence or breast cancer-specific mortality between atenolol users and matched nonusers. The results provide evidence in humans to support preclinical observations suggesting that inhibiting the β₂-adrenergic signaling pathway can reduce breast cancer progression and mortality.

  7. Mechanisms of atrial fibrillation termination by rapidly unbinding Na+ channel blockers: insights from mathematical models and experimental correlates.

    Science.gov (United States)

    Comtois, Philippe; Sakabe, Masao; Vigmond, Edward J; Munoz, Mauricio; Texier, Anne; Shiroshita-Takeshita, Akiko; Nattel, Stanley

    2008-10-01

    Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is a problem of growing proportions. Recent studies have increased interest in fast-unbinding Na(+) channel blockers like vernakalant (RSD1235) and ranolazine for AF therapy, but the mechanism of efficacy is poorly understood. To study how fast-unbinding I(Na) blockers affect AF, we developed realistic mathematical models of state-dependent Na(+) channel block, using a lidocaine model as a prototype, and studied the effects on simulated cholinergic AF in two- and three-dimensional atrial substrates. We then compared the results with in vivo effects of lidocaine on vagotonic AF in dogs. Lidocaine action was modeled with the Hondeghem-Katzung modulated-receptor theory and maximum affinity for activated Na(+) channels. Lidocaine produced frequency-dependent Na(+) channel blocking and conduction slowing effects and terminated AF in both two- and three-dimensional models with concentration-dependent efficacy (maximum approximately 89% at 60 microM). AF termination was not related to increases in wavelength, which tended to decrease with the drug, but rather to decreased source Na(+) current in the face of large ACh-sensitive K(+) current-related sinks, leading to the destabilization of primary generator rotors and a great reduction in wavebreak, which caused primary rotor annihilations in the absence of secondary rotors to resume generator activity. Lidocaine also reduced the variability and maximum values of the dominant frequency distribution during AF. Qualitatively similar results were obtained in vivo for lidocaine effects on vagal AF in dogs, with an efficacy of 86% at 2 mg/kg iv, as well as with simulations using the guarded-receptor model of lidocaine action. These results provide new insights into the mechanisms by which rapidly unbinding class I antiarrhythmic agents, a class including several novel compounds of considerable promise, terminate AF.

  8. 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

  9. Uptitration of renin-angiotensin system blocker and beta-blocker therapy in patients hospitalized for heart failure with reduced versus preserved left ventricular ejection fractions.

    Science.gov (United States)

    Verbrugge, Frederik H; Duchenne, Jürgen; Bertrand, Philippe B; Dupont, Matthias; Tang, W H Wilson; Mullens, Wilfried

    2013-12-15

    In ambulatory patients with heart failure (HF) and reduced ejection fraction (rEF), renin-angiotensin system (RAS) and β-blockers at guideline-recommended target dose reduce all-cause mortality and readmissions. Benefits in HF with preserved ejection fraction (pEF), as well as uptitration after a hospitalization, remain uncertain. This study assesses the impact of RAS- and β-blocker uptitrations in patients with HFrEF versus HFpEF during and immediately after a hospital admission. In consecutive patients (209 HFrEF with left ventricular ejection fraction blocker dose changes were followed during 6 months after an index HF hospitalization. Patients with a RAS- and β-blocker dose increase of ≥10% of the recommended target dose were compared with patients without uptitration. Patients who received uptitration were significantly younger, with a higher heart rate and better renal function, and received spironolactone more often. Both RAS- and β-blocker uptitrations were associated with significant reductions in the composite end-point of all-cause mortality or HF readmissions in HFrEF (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.22 to 0.60 and HR 0.51, 95% CI 0.32 to 0.81, respectively). After correction for age, heart rate, blood pressure, renal function, and spironolactone use, this association remained significant for RAS blockers (HR 0.54, 95% CI 0.31 to 0.93, p = 0.027) but not for β-blockers (HR 0.65, 95% CI 0.39 to 1.09, p = 0.101). No benefit of RAS- or β-blocker uptitration was observed in HFpEF. In conclusion, uptitration of neurohumoral blockers after an HF hospitalization is more frequently performed in younger patients with low co-morbidity burden. RAS-blocker uptitration independently predicts clinical outcome in patients with HFrEF but not in those with HFpEF. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. A Regional Quality Improvement Effort to Increase Beta Blocker Administration Before Vascular Surgery

    Science.gov (United States)

    Goodney, Philip P.; Eldrup-Jorgensen, Jens; Nolan, Brian W.; Bertges, Daniel J.; Likosky, Donald S.; Cronenwett, Jack L.

    2011-01-01

    Objective To determine if a regional quality improvement effort can increase beta-blocker utilization prior to vascular surgery and decrease the incidence of post-op myocardial infarction (POMI). Methods A quality improvement effort to increase peri-operative beta blocker utilization was implemented in 2003 at centers participating in the Vascular Study Group of New England (VSGNE). A 90% target was set and feedback given at bi-annual meetings. Beta blocker utilization (beta blocker administration and POMI were analyzed over time, and across strata of patient risk based on a multivariate model. Results Peri-operative beta blocker treatment increased from 68% of patients in the first three months of 2005 to 88% by the last 3 months of 2008 (pbeta blockers were treated with pre-operative beta blockers; by 2008, 78% of patients not on chronic beta blockers were started peri-operatively on these medications (pBeta blocker utilization increased across all centers and surgeons participating during the study period, and increased in patients of low, medium, and high cardiac risk. However, the rate of POMI did not change over time (5.2% in 2003, 5.5% in 2008, p=0.876), although a trend towards lower POMI rate was seen in patients on pre-operative beta blockers (4.4% in 2003-2005, 2.6% in 2006-2008, p=0.43). In multivariable modeling we found that age >70 (OR 2.1), positive stress test (OR 2.2), CHF (OR 1.7), chronic beta blocker administration (OR 1.7), resting heart rate (HR) beta blockers (70) (p=0.521). Conclusions Our regional quality improvement effort successfully increased peri-operative beta blocker utilization. However, this was not associated with reduced rates of POMI or resting heart rate. While this demonstrates the effectiveness of regional quality improvement efforts in changing practice patterns, further work is necessary to more precisely identify those patients who will benefit from beta blockade at the time of vascular surgery. PMID:21334166

  11. Use of angiotensin II receptor blockers in children- a review of ...

    African Journals Online (AJOL)

    Background: The incidence of hypertension in the pediatric population has been increasing. Childhood blood pressure is predictive of adult BP. The renin angiotensin aldosterone system pathway is important in the mediation of pediatric hypertension. New therapies approved for adults are often used off label in children ...

  12. Use of angiotensin II receptor blockers in children- a review of ...

    African Journals Online (AJOL)

    2015-05-19

    May 19, 2015 ... hypertension and proteinuria in renal disease. Safety pharmacokinetic, dosage, issues of paediatric formu- .... ated in children (1-17 years old) with proteinuria secon- dary to Alport syndrome. Losartan maintained proteinu- ..... experience. J Pediatr. 2007;150:134 –139. 55. Wells TG, Blowey DL , Sullivan.

  13. Parturition induction in ewes by a progesterone receptor blocker, aglepristone, and subsequent neonatal survival: Preliminary results.

    Science.gov (United States)

    Özalp, R G; Yavuz, A; Orman, A; Seker, I; Udum Küçükşen, D; Rişvanlı, A; Demiral, Ö O; Wehrend, A

    2017-01-01

    The clinical effects of aglepristone treatment to induce parturition in ewes and their newborns were reported. Three experimental groups were defined: group AG5 (n = 5), group AG10 (n = 5), and group CG (n = 5) in which ewes were injected twice with 5, 10 mg/kg of aglepristone, and saline solution of ewes, respectively. Different parameters associated with parturition in ewes and their newborns were investigated. Serum progesterone, oxytocin, and free and conjugated total estrogens were measured after treatments until parturition. No statistical difference was found from first aglepristone administration to onset of lambing between AG5 and AG10 (23.90 ± 6.20, 40.00 ± 6.71 hours). Parturition induction in two groups shortened the gestational length significantly compared with the control group (P = 0.003). Dystocia was observed in two ewes in group AG10. The placental weight showed statistically significant difference only between the AG10 and CG (P = 0.039), but no difference was observed in the placental expulsion period between the groups. Decrease in food consumption 24 to 36 hours after parturition in all ewes and skin necrosis in an ewe in group AG5 were observed. Progesterone concentration was significantly lower in AG5 than that in ewes in group AG10 and CG (P birth weight (4.29 ± 0.28 kg), which was significantly different from the induced groups. No significant difference of blood pH and blood gases values between groups was identified both at birth and 12 hours after parturition for lambs. Significant differences could clearly be observed in total protein and blood urea nitrogen and total protein findings 12 hours after parturition (P control lambing time without any side effects in either mothers or lambs. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. GH receptor blocker administration and muscle-tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Nielsen, Rie Harboe; Doessing, Simon; Goto, Kazushige

    2011-01-01

    The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans.......The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans....

  16. GH receptor blocker administration and muscle-tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Nielsen, Rie H; Doessing, Simon; Goto, K.

    2011-01-01

    Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing......, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1......] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection...

  17. Evaluation of the angiotensin II receptor blocker azilsartan medoxomil in African-American patients with hypertension.

    Science.gov (United States)

    Johnson, Wallace; White, William B; Sica, Domenic; Bakris, George L; Weber, Michael A; Handley, Alison; Perez, Alfonso; Cao, Charlie; Kupfer, Stuart; Saunders, Elijah B

    2017-07-01

    The efficacy and safety of azilsartan medoxomil (AZL-M) were evaluated in African-American patients with hypertension in a 6-week, double-blind, randomized, placebo-controlled trial, for which the primary end point was change from baseline in 24-hour mean systolic blood pressure (BP). There were 413 patients, with a mean age of 52 years, 57% women, and baseline 24-hour BP of 146/91 mm Hg. Treatment differences in 24-hour systolic BP between AZL-M 40 mg and placebo (-5.0 mm Hg; 95% confidence interval, -8.0 to -2.0) and AZL-M 80 mg and placebo (-7.8 mm Hg; 95% confidence interval, -10.7 to -4.9) were significant (P≤.001 vs placebo for both comparisons). Changes in the clinic BPs were similar to the ambulatory BP results. Incidence rates of adverse events were comparable among the treatment groups, including those of a serious nature. In African-American patients with hypertension, AZL-M significantly reduced ambulatory and clinic BPs in a dose-dependent manner and was well tolerated. © The Authors and Takeda Development Centers, Americas, Inc and Takeda Pharmaceuticals International. The Journal of Clinical Hypertension published by Wiley Periodicals, Inc.

  18. Evaluation of angiotensin II receptor blockers for drug formulary using objective scoring analytical tool

    Directory of Open Access Journals (Sweden)

    Lim TM

    2012-09-01

    Full Text Available Drug selection methods with scores have been developed and used worldwide for formulary purposes. These tools focus on the way in which the products are differentiated from each other within the same therapeutic class. Scoring Analytical Tool (SAT is designed based on the same principle with score and is able to assist formulary committee members in evaluating drugs either to add or delete in a more structured, consistent and reproducible manner. Objective: To develop an objective SAT to facilitate evaluation of drug selection for formulary listing purposes. Methods: A cross-sectional survey was carried out. The proposed SAT was developed to evaluate the drugs according to pre-set criteria and sub-criteria that were matched to the diseases concerned and scores were then assigned based on their relative importance. The main criteria under consideration were safety, quality, cost and efficacy. All these were converted to questionnaires format. Data and information were collected through self-administered questionnaires that were distributed to medical doctors and specialists from the established public hospitals. A convenient sample of 167 doctors (specialists and non-specialists were taken from various disciplines in the outpatient clinics such as Medical, Nephrology and Cardiology units who prescribed ARBs hypertensive drugs to patients. They were given a duration of 4 weeks to answer the questionnaires at their convenience. One way ANOVA, Kruskal Wallis and post hoc comparison tests were carried out at alpha level 0.05. Results: Statistical analysis showed that the descending order of ARBs preference was Telmisartan or Irbesartan or Losartan, Valsartan or Candesartan, Olmesartan and lastly Eprosartan. The most cost saving ARBs for hypertension in public hospitals was Irbesartan. Conclusion: SAT is a tool which can be used to reduce the number of drugs and retained the most therapeutically appropriate drugs in the formulary, to determine most cost saving drugs and has the potential to complement the conventional method of drug selection as it is effective in aiding decision making process through the pre-established criteria and increasing scientific ground of decisions and transparency.

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

    OpenAIRE

    Cernes R; Mashavi M; Zimlichman R

    2011-01-01

    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...

  20. Interaction of selected vasodilating beta-blockers with adrenergic receptors in human cardiovascular tissues

    Energy Technology Data Exchange (ETDEWEB)

    Monopoli, A.; Forlani, A.; Bevilacqua, M.; Vago, T.; Norbiato, G.; Bertora, P.; Biglioli, P.; Alamanni, F.; Ongini, E. (Essex Italia, Subsidiary of Schering-Plough, Milan)

    1989-07-01

    beta- And alpha 1-adrenoceptor antagonist properties of bufuralol, carvedilol, celiprolol, dilevalol, labetalol, and pindolol were investigated in human myocardium and mammary artery using binding techniques and functional studies. In myocardial membranes, beta-adrenoceptor antagonists showed monophasic competition isotherms for (125I)pindolol binding with high affinity (Ki from 1-100 nM), except for celiprolol which displayed a biphasic competition isotherm (pKi = 6.4 +/- 0.06 for beta 1- and 4.8 +/- 0.07 for beta 2-adrenoceptors). Drug interactions with alpha 1-adrenoceptors were evaluated in human mammary artery by (3H)prazosin binding and by measuring contractile responses to norepinephrine (NE). Labetalol and carvedilol showed a moderate affinity for alpha 1-adrenoceptors (pKi = 6.2 +/- 0.01 and 6.1 +/- 0.06, respectively), and inhibited NE-induced contractions (pA2 = 6.93 +/- 0.23 and 8.64 +/- 0.24, respectively). Dilevalol, bufuralol, and pindolol displayed weak effect both in binding (Ki in micromolar range) and functional experiments (pA2 = 5.98, 5.54, and 6.23, respectively). Celiprolol did not show antagonist properties up to 100 microM in functional studies, but displayed a slight affinity for alpha 1-adrenoceptors in binding studies. The data indicate that the vasodilating activity of these beta-adrenoceptor antagonists is caused in some instances by an alpha 1-adrenoceptor antagonism (labetalol, carvedilol), whereas for the others alternative mechanisms should be considered.

  1. 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

  2. Divergent action of calcium channel blockers on ATP-binding cassette protein expression.

    Science.gov (United States)

    Hasegawa, Kazuhiro; Wakino, Shu; Kanda, Takeshi; Yoshioka, Kyoko; Tatematsu, Satoru; Homma, Koichiro; Takamatsu, Ichiro; Sugano, Naoki; Hayashi, Koichi

    2005-12-01

    Calcium channel blockers (CCBs) are widely used in clinical practice, and have been reported to be effective in preventing the progression of atherosclerosis. We examined whether various types of calcium channel blockers affected the expression of ATP binding cassette transporter A1 (ABCA1), a factor contributing to anti-atherogenesis. Undifferentiated monocytic cell line, THP-1 cells were maintained in RPMI 1640 medium and treated with different kinds of calcium channel blockers. Among the calcium channel blockers tested, aranidipine and efonidipine increased ABCA1 protein expression without an increase in ABCA1 mRNA expression, whereas other calcium channel blockers (eg, nifedipine, amlodipine, and nicardipine) or T-type calcium channel blockers (eg, mibefradil and nickel chloride) failed to upregulate ABCA1 expression. H89, a protein kinase A inhibitor inhibited the aranidipine-induced ABCA1 protein expression, whereas genistein (a tyrosine kinase inhibitor), or AG490 (a JAK-2 inhibitor) had no effects. Neither of these inhibitors suppressed the efonidipine-induced ABCA1 protein expression. Intracellular cAMP levels were elevated only by aranidipine, but not by efonidipine. In conclusion, aranidipine and efonidipine have the ability to induce ABCA1 protein by distinct mechanisms; protein kinase A is involved in the aranidipine-induced ABCA1 upregulation. This non-class effect of calcium channel blockers may potentially offer beneficial action in the treatment of hypertensive subjects with atherosclerosis.

  3. 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

  4. Effect of Preoperative Beta-Blocker Use on Outcomes Following Cardiac Surgery.

    Science.gov (United States)

    O'Neal, Jason B; Billings, Frederic T; Liu, Xulei; Shotwell, Matthew S; Liang, Yafen; Shah, Ashish S; Ehrenfeld, Jesse M; Wanderer, Jonathan P; Shaw, Andrew D

    2017-10-15

    Recent studies suggest that the use of preoperative β blockers in cardiac surgery may not provide improved mortality rates and may even contribute to negative clinical outcomes. We therefore assessed the role of β blockers on several outcomes after cardiac surgery (delirium, acute kidney injury [AKI], stroke, atrial fibrillation (AF), mortality, and hospital length of stay) in 4,076 patients who underwent elective coronary artery bypass grafting, coronary artery bypass grafting + valve, or valve cardiac surgery from November 1, 2009, to September 30, 2015, at Vanderbilt Medical Center. Clinical data from 2 prospectively collected datasets at our institution were reviewed: the Cardiac Surgery Perioperative Outcomes Database and the Society of Thoracic Surgeons Database. Preoperative β-blocker use was defined by Society of Thoracic Surgeons guidelines as patients receiving a β blocker within 24 hours preceding surgery. Of the included patients, 2,648 (65.0%) were administered a β blocker within 24 hours before surgery. Adjusting for possible confounders, preoperative β-blocker use was associated with increased odds of AKI stage 2 (odds ratio 1.96, 95% confidence interval 1.19 to 3.24, p blocker use had an independent association with postoperative delirium, AKI stages 1 and 3, stroke, AF, mortality, or prolonged length of stay. A secondary propensity score analysis did not show a marginal association between β-blocker use and any outcome. In conclusion, we did not find significant evidence that preoperative β-blocker use was associated with postoperative delirium, AF, AKI, stroke, or mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Stage-specific associations between beta blocker use and prognosis after colorectal cancer.

    Science.gov (United States)

    Jansen, Lina; Hoffmeister, Michael; Arndt, Volker; Chang-Claude, Jenny; Brenner, Hermann

    2014-04-15

    Recent observational studies have suggested that the use of beta blockers might be associated with better prognosis after cancer. Because evidence is limited for colorectal cancer (CRC), the association of beta blocker use and prognosis was investigated in a large population-based cohort of patients with CRC. Between 2003 and 2007, information on beta blocker use at diagnosis and potential confounders was collected by personal interviews for 1975 patients with CRC. Vital status, cause of death, and recurrence status were assessed during a median follow-up time of 5.0 years. The associations of beta blocker use and overall, CRC-specific, and recurrence-free survival were estimated by Cox proportional hazard regression. In addition, beta blocker subgroup, site, and stage-specific analyses were performed. After adjustment for covariates including sociodemographic, cancer-related, and lifestyle factors and comorbidity and medications, no significant association between beta blocker use at diagnosis and prognosis was observed for all stages combined. However, in stage-specific analyses, beta blocker use was associated with longer overall survival (hazard ratio = 0.50; 95% confidence interval = 0.33-0.78) and CRC-specific survival (hazard ratio = 0.47; 95% confidence interval = 0.30-0.75) in stage IV patients. For these patients, median overall survival was 18 months longer and CRC-specific survival was 17 months longer for beta blocker users than for nonusers (38 versus 20 months and 37 versus 20 months, respectively). These results suggest that beta blocker use might be associated with longer survival in patients with stage IV CRC. © 2013 American Cancer Society.

  6. Developing Memory Reconsolidation Blockers as Novel PTSD Treatments

    Science.gov (United States)

    2011-06-01

    metabotropic glutamate receptor. These results suggest a previously unknown mechanism by which the hierarchy of coexisting forms of long-term synaptic...3 different countries with men and women, but a lack of participants of minority ethnicity limits the generalizability of the findings. In study 3...metabotropic glutamate receptor. These results suggest a previously unknown mechanism by which the hierarchy of coexisting forms of long-term synaptic

  7. Initiation of Beta-Blocker Therapy and Depression After Acute Myocardial Infarction

    Science.gov (United States)

    Ranchord, Anil M.; Spertus, John A.; Buchanan, Donna M.; Gosch, Kensey L.; Chan, Paul S.

    2016-01-01

    Introduction Although beta (β)-blockers reduce mortality after acute myocardial infarction (AMI), early reports linking β-blocker use with subsequent depression have potentially limited their use in vulnerable patients. We sought to provide empirical evidence to support or refute this concern by examining the association between β-blocker initiation and change in depressive symptoms in AMI patients. Methods Using data from 2 US multi-center, prospective registries of AMI patients, we examined 1-, 6-, and 12-month changes in depressive symptoms after the index hospitalization among patients who were β-blocker naïve on admission. Depressive symptoms were assessed using the validated 8-item Patient Health Questionnaire (PHQ-8), which rates depressive symptoms from 0 to 24, with higher scores indicating more depressive symptoms. A propensity-matched repeated measures linear regression model was used to compare change in depressive symptoms among patients who were and were not initiated on a β-blocker after AMI. Results Of 3470 AMI patients who were β-blocker naïve on admission, 3190 (91.9%) were initiated on a β-blocker and 280 (8.1%) were not. Baseline PHQ-8 scores were higher in patients not initiated on a β-blocker (mean 5.78 ± 5.45 vs. 4.88 ± 5.11, P=0.005). PHQ-8 scores were progressively lower at 1, 6 and 12 months in both the β-blocker (mean decrease at 12 months, 1.16; pblocker groups (mean decrease, 1.71; pblocker therapy was not associated with a difference in mean change in PHQ-8 scores at 1, 6 or 12 months after AMI (absolute mean difference with β-blocker initiation at 12 months of 0.08, 95% CI: −0.81 to 0.96, P=0.86). Conclusions Initiation of β-blocker therapy after AMI was not associated with an increase in depressive symptoms. Restricting β-blocker use because of concerns about depression appears unwarranted and may lead to under-treatment of AMI patients. PMID:26995368

  8. Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction.

    Science.gov (United States)

    Goldberger, Jeffrey J; Bonow, Robert O; Cuffe, Michael; Liu, Lei; Rosenberg, Yves; Shah, Prediman K; Smith, Sidney C; Subačius, Haris

    2015-09-29

    Beta-blocker therapy after acute myocardial infarction (MI) improves survival. Beta-blocker doses used in clinical practice are often substantially lower than those used in the randomized trials establishing their efficacy. This study evaluated the association of beta-blocker dose with survival after acute MI, hypothesizing that higher dose beta-blocker therapy will be associated with increased survival. A multicenter registry enrolled 7,057 consecutive patients with acute MI. Discharge beta-blocker dose was indexed to the target beta-blocker doses used in randomized clinical trials, grouped as >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target dose. Follow-up vital status was assessed, with the primary endpoint of time-to-death right-censored at 2 years. Multivariable and propensity score analyses were used to account for group differences. Of 6,682 patients with follow-up (median 2.1 years), 91.5% were discharged on a beta-blocker (mean dose 38.1% of the target dose). Lower mortality was observed with all beta-blocker doses (p beta-blocker therapy. After multivariable adjustment, hazard ratios for 2-year mortality compared with the >50% dose were 0.862 (95% confidence interval [CI]: 0.677 to 1.098), 0.799 (95% CI: 0.635 to 1.005), and 0.963 (95% CI: 0.765 to 1.213) for the >0% to 12.5%, >12.5% to 25%, and >25% to 50% of target dose groups, respectively. Multivariable analysis with an extended set of covariates and propensity score analysis also demonstrated that higher doses were not associated with better outcome. These data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in previous randomized clinical trials compared with lower doses. These findings provide the rationale to re-engage in research to establish appropriate beta-blocker dosing after MI to derive optimal benefit from this therapy. (The PACE-MI Registry Study-Outcomes of Beta-blocker Therapy After Myocardial Infarction [OBTAIN

  9. Type of Beta-blocker Use Among Patients with Versus without Diabetes after Myocardial Infarction

    Science.gov (United States)

    Arnold, Suzanne V.; Spertus, John A.; Lipska, Kasia J.; Lanfear, David E.; Tang, Fengming; Grodzinsky, Anna; McGuire, Darren K.; Gore, M. Odette; Goyal, Abhinav; Maddox, Thomas M.; Kosiborod, Mikhail

    2014-01-01

    Background Discharge beta-blocker prescription after myocardial infarction (MI) is recommended for all eligible patients. Numerous beta-blocker choices are presently available with variable glycometabolic effects, which could be an important consideration in patients with diabetes mellitus (DM). Whether patients with DM preferentially receive beta-blockers with favorable metabolic effects after MI and if this choice is associated with better glycemic control post-discharge is unknown. Methods Among patients from 24 US hospitals enrolled in an MI registry (2005–08), we investigated the frequency of “DM-friendly” beta-blocker prescription at discharge by DM status. Beta-blockers were classified as DM-friendly (e.g., carvedilol, labetalol), or non-DM-friendly (e.g., metoprolol, atenolol), based on their effects on glycemic control. Hierarchical, multivariable logistic regression examined the association of DM with DM-friendly beta-blocker use. Among DM patients, we examined the association of DM-friendly beta-blockers with worsened glycemic control at 6 months after MI. Results Of 4031 MI patients, 1382 (34%) had DM. Beta-blockers were prescribed at discharge in 93% of patients. DM-friendly beta-blocker use was low regardless of DM status, although patients with DM were more likely to be discharged on a DM-friendly beta-blocker compared with patients without DM (13.5% vs. 10.3%, p=0.003), an association that remained after multivariable adjustment (OR 1.41, 95% CI 1.13–1.77). There was a trend toward a lower risk of worsened glucose control at 6 months in DM patients prescribed DM-friendly vs. non-friendly beta-blockers (RR 0.80, 95% CI 0.60–1.08). Conclusion The vast majority of DM patients were prescribed non-DM friendly beta-blockers—a practice that was associated with a trend towards worse glycemic control post-discharge. While in need of further confirmation in larger studies, our findings highlight an opportunity to improve current practices of beta-blockers

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

    Science.gov (United States)

    Butt, Jawad H; Dalsgaard, Søren; Torp-Pedersen, Christian; Køber, Lars; Gislason, Gunnar H; Kruuse, Christina; Fosbøl, Emil L

    2017-04-01

    Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students at risk of later psychiatric events. Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical 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 for unadjusted associations and multivariable cause-specific Cox proportional hazard analyses for adjusted hazard ratios (HRs). We identified 12,147 healthy students with exam-related beta-blocker use and 12,147 matched healthy students with no current or prior use of beta-blockers (median age, 19 years; 80.3% women). Among all healthy students, 0.14% had a first-time prescription for a beta-blocker during the exam period with the highest proportion among students aged 19 years (0.39%). Eighty-one percent of the students filled only that single prescription for a beta-blocker during follow-up. During follow-up, 2225 (18.3%) beta-blocker users and 1400 (11.5%) nonbeta-blocker users were prescribed an antidepressant (p 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 exam period was associated with an increased risk of psychiatric outcomes and might identify psychologically vulnerable students who need special attention.

  11. 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......-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 suicide attempts...

  12. 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...

  13. THE CHOICE OF DRUG FROM THE STANDPOINT OF EVIDENCE-BASED MEDICINE: CASE STUDY OF BETA-BLOCKERS

    Directory of Open Access Journals (Sweden)

    S. Yu. Martsevich

    2010-01-01

    Full Text Available Basic principles of beta-blockers choice strategy are presented. Attention is focused on the facts concerning the evidence base for effects of various beta-blockers on the outcomes of cardiovascular diseases. Beta-blocker indications and safety of their long-term use are considered from this point of view. Convincing data about beta-blocker impact on the prognosis of cardiovascular disease should be the reason for any beta-blocker choice, as well as choice of their doses which were tested in large randomized trials.

  14. Calcium channels and their blockers in intraocular pressure and glaucoma.

    Science.gov (United States)

    Mayama, Chihiro

    2014-09-15

    Several factors besides high intraocular pressure assumed to be associated with the development and progression of glaucoma, and calcium channel blockers (CCBs) have been an anticipated option for glaucoma treatment by improving ocular perfusion and/or exerting neuroprotective effects on retinal ganglion cells with safety established in wide and long-term usage. Decrease in IOP has been reported after topical application of CCBs, however, the effect is much smaller and almost negligible after systemic application. Various CCBs have been reported to increase posterior ocular blood flow in vivo and to exert direct neuroprotection in neurons in vitro. Distribution of the drug at a pharmacologically active concentration in the posterior ocular tissues across the blood-brain barrier or blood-retina barrier, especially in the optic nerve head and retina where the ganglion cells mainly suffer from glaucomatous damage, is essential for clinical treatment of glaucoma. Improved visual functions such as sensitivity in the visual field test have been reported after administration of CCBs, but evidences from the randomized studies have been limited and effects of CCBs on blood flow and direct neuroprotection are hardly distinguished from each other. © 2013 Published by Elsevier B.V.

  15. 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.

  16. Meroterpenoid Chrodrimanins Are Selective and Potent Blockers of Insect GABA-Gated Chloride Channels.

    Directory of Open Access Journals (Sweden)

    Yan Xu

    Full Text Available Meroterpenoid chrodrimanins, produced from Talaromyces sp. YO-2, are known to paralyze silkworm (Bombyx mori larvae, but their target is unknown. We have investigated the actions of chrodrimanin B on ligand-gated ion channels of silkworm larval neurons using patch-clamp electrophysiology. Chrodrimanin B had no effect on membrane currents when tested alone at 1 μM. However, it completely blocked the γ-aminobutyric acid (GABA-induced current and showed less pronounced actions on acetylcholine- and L-glutamate-induced currents, when delivered at 1 μM for 1 min prior to co-application with transmitter GABA. Thus, chrodrimanins were also tested on a wild-type isoform of the B. mori GABA receptor (GABAR RDL using two-electrode voltage-clamp electrophysiology. Chrodrimanin B attenuated the peak current amplitude of the GABA response of RDL with an IC50 of 1.66 nM. The order of the GABAR-blocking potency of chrodrimanins B > D > A was in accordance with their reported insecticidal potency. Chrodrimanin B had no open channel blocking action when tested at 3 nM on the GABA response of RDL. Co-application with 3 nM chrodrimanin B shifted the GABA concentration response curve to a higher concentration and further increase of chrodrimanin B concentration to 10 nM; it reduced maximum current amplitude of the GABA response, pointing to a high-affinity competitive action and a lower affinity non-competitive action. The A282S;T286V double mutation of RDL, which impairs the actions of fipronil, hardly affected the blocking action of chrodrimanin B, indicating a binding site of chrodrimanin B distinct from that of fipronil. Chrodrimanin B showed approximately 1,000-fold lower blocking action on human α1β2γ2 GABAR compared to RDL and thus is a selective blocker of insect GABARs.

  17. 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

  18. 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

    Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular...... 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...... reduce hepatic inflammation. Blockage of β-adrenoceptors also decrease angiogenesis by inhibition of vascular endothelial growth factors. Because gut-derived inflammation and neo-angiogenesis are important in hepatic carcinogenesis, non-selective beta-blockers can potentially reduce the development...

  19. Comparison of the clinical outcome of different beta-blockers in heart failure patients

    DEFF Research Database (Denmark)

    Bølling, Rasmus; Scheller, Nikolai Madrid; Køber, Lars

    2014-01-01

    AIM: To compare survival on different beta-blockers in heart failure. METHODS AND RESULTS: We identified all Danish patients ≥35 years of age who were hospitalized with a first admission for heart failure and who initiated treatment with a beta-blocker within 60 days of discharge. The study period....... In an unadjusted model carvedilol was associated with a lower mortality [hazard ratio (HR) 0.737, 0.714-0.761] compared with metoprolol (reference) while bisoprolol was not associated with an increased mortality (HR 1.020, 0.973-1.069). In a model adjusted for possible confounders and stratified according to beta-blocker...... receiving high-dose carvedilol (≥50 mg daily) showed significantly lower all-cause mortality risk and hospitalization risk, compared with other beta-blockers....

  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

    Aims: Beta-blockers vary in pharmacodynamics and pharmacokinetic properties. It is unknown whether specific types are associated with increased perioperative risks. We evaluated perioperative risks associated with beta-blocker subtypes, overall and in patient subgroups. Methods and results: We...... 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...... in analyses stratified by age, surgery priority, duration of anaesthesia or surgery risk (all P for interaction >0.05). Conclusion: Risks of ACM and MACE did not systematically differ by beta-blocker subtype. Findings may guide clinical practice and future trials....

  1. β-blocker-associated risks in patients with uncomplicated hypertension undergoing noncardiac surgery

    DEFF Research Database (Denmark)

    Jørgensen, Mads E.; Hlatky, Mark A.; Køber, Lars

    2015-01-01

    IMPORTANCE: Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk. OBJECTIVE: To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy...... antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. INTERVENTIONS: Various antihypertensive treatment regimens, chosen as part of usual care. MAIN OUTCOMES AND MEASURES: Thirty-day risk of MACEs...... (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...

  2. 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.

    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

  3. 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.

  4. Differential Effects of β-Blockers on Albuminuria in Patients With Type 2 Diabetes

    National Research Council Canada - National Science Library

    Bakris, George L; Fonseca, Vivian; Katholi, Richard E; McGill, Janet B; Messerli, Franz; Phillips, Robert A; Raskin, Philip; Wright, Jr, Jackson T; Waterhouse, Brian; Lukas, Mary Ann; Anderson, Karen M; Bell, David S.H

    2005-01-01

    .... Such changes in microalbuminuria have not been observed when β-blockers are used. A prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI...

  5. 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...... HCC-related mortality (RD -0.011; 95% CI -0.040 to 0.017). CONCLUSIONS: Non-selective beta-blockers may prevent HCC in patients with cirrhosis....

  6. The high frequency relationship: implications for torsadogenic hERG blockers.

    Science.gov (United States)

    Champeroux, P; Le Guennec, J Y; Jude, S; Laigot, C; Maurin, A; Sola, M L; Fowler, J S L; Richard, S; Thireau, J

    2016-02-01

    Ventricular arrhythmias induced by human ether-a-go-go related gene (hERG; Kv 11.1 channel) blockers are a consequence of alterations in ventricular repolarisation in association with high-frequency (HF) oscillations, which act as a primary trigger; the autonomic nervous system plays a modulatory role. In the present study, we investigated the role of β1 -adrenoceptors in the HF relationship between magnitude of heart rate and QT interval changes within discrete 10 s intervals (sorted into 5 bpm heart rate increments) and its implications for torsadogenic hERG blockers. The HF relationship was studied under conditions of autonomic blockade with atenolol (β1 -adrenoceptor blocker) in the absence or presence of five hERG blockers in beagle dogs. In total, the effects of 14 hERG blockers on the HF relationship were investigated. All the torsadogenic hERG blockers tested caused a vertical shift in the HF relationship, while hERG blockers associated with a low risk of Torsades de Pointes did not cause any vertical shift. Atenolol completely prevented the effects four torsadogenic agents (quinidine, thioridazine, risperidone and terfenadine) on the HF relationship, but only partially reduced those of dofetilide, leading to the characterization of two types of torsadogenic agent. Analysis of the vertical shift in the HF relationship demonstrated that signs of transient sympathetic activation during HF oscillations in the presence of torsadogenic hERG blockers are mediated by β1 -adrenoceptors. We suggest the HF relationship as a new biomarker for assessing Torsades de pointes liability, with potential implications in both preclinical studies and the clinic. © 2015 The British Pharmacological Society.

  7. Predictors of Therapeutic Response to Beta-blockers in Patients with Heart Failure in Taiwan

    Directory of Open Access Journals (Sweden)

    Hsin Hu

    2007-08-01

    Conclusion: We demonstrated the therapeutic effects of β-blockers in Taiwanese HF patients with a dose lower than what has been reported in Western people. Moreover, patients with the etiology of dilated cardiomyopathy or lower baseline LVEF predicted a greater LVEF improvement. The β1-adrenoceptor gene polymorphisms were not responsible for the difference in sensitivity to β-blockers in this Taiwanese population.

  8. Evaluation of beta-blockers and survival among hypertensive patients with renal cell carcinoma.

    Science.gov (United States)

    Parker, William P; Lohse, Christine M; Zaid, Harras B; Cheville, John C; Boorjian, Stephen A; Leibovich, Bradley C; Thompson, R Houston

    2017-01-01

    Beta-blocker use is associated with improved survival for multiple nonurologic malignancies. Our objective was to evaluate the association between beta-blocker use and survival among surgically managed hypertensive patients with clear-cell renal cell carcinoma (ccRCC). Hypertensive patients with ccRCC treated with either radical or partial nephrectomy between 2000 and 2010 were identified from our Nephrectomy Registry. Beta-blocker use within 90 days before surgery was identified. The associations between beta-blocker use and risk of disease progression, death from renal cell carcinoma (RCC), and all-cause mortality were assessed using Cox proportional hazards regression models. In total, 913 hypertensive patients were identified who underwent either partial or radical nephrectomy for ccRCC. Of these, 104 (11%) had documented beta-blocker use within 90 days before surgery. At last follow-up (median 8.2y among survivors), 258 patients showed progression (median 1.6y following surgery), and 369 patients had died (median 4.1y following surgery), including 138 who died of RCC. After adjusting for PROG (progression-free survival) and SSIGN (cancer-specific survival) scores, beta-blocker use was not significantly associated with the risk of disease progression (hazard ratio [HR] = 0.94; 95% CI: 0.61-1.47; P = 0.80) or the risk of death from RCC (HR = 0.74; 95% CI: 0.38-1.41; P = 0.35). Similarly, on multivariable analysis adjusting for clinicopathologic features, there was not a significant association between beta-blocker use and the risk of all-cause mortality (HR = 0.83; 95% CI: 0.59-1.16; P = 0.27). Beta-blocker use for hypertension within 90 days before surgery was not associated with the risk of progression, death from RCC, or death from any cause. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. [Could treatments with beta-blockers be associated with a reduction in cancer risk?].

    Science.gov (United States)

    Algazi, M; Plu-Bureau, G; Flahault, A; Dondon, M-G; Lê, M G

    2004-02-01

    The relationship between the use of anti-hypertensive drugs and cancer risk remains controversial. The main objective of this study was to assess the potential effect of beta-blocker use on cancer risk. In a cohort of 839 patients with cardiovascular disease, followed up prospectively for an average period of 10 years, cancer occurrence was recorded according to the exposure to beta-blockers. The relative risk of cancer associated with beta-blocker use was estimated using a Cox model adjusted on gender and age. Ever- vs never-use of beta-blockers and duration of exposure to the drug were analyzed as time-dependent variables. In addition, the standardized incidence ratios (SIR) were calculated using the corresponding age- and gender-adjusted cancer incidences in the French general population. A total of 326 beta-blocker users and 513 users of other treatments were included in the cohort. During the follow-up period, representing 8,466 person-years, incident cancer cases were 15 and 59 in beta-blocker ever-users versus never-users, respectively. Using the Cox model, the overall relative risk of cancer was 0.51 (95% confidence interval [95% CI]: 0.29-0.90) in the beta-blocker ever-users versus never-users (p=0.02), with a 6% decrease per year of use (95% CI: 1%-12%; p=0.03). The corresponding SIR ratio between these two groups was 0.44 (95% CI: 0.24-0.76). In this cohort, the beta-blocker treatments appeared to decrease the cancer risk significantly. However, this result should be considered with caution; further work is needed, as some sources of bias associated with this type of epidemiological study cannot be totally excluded.

  10. The effectiveness of beta-blockers after myocardial infarction in patients with type 2 diabetes.

    Science.gov (United States)

    McDonald, Charlotte G; Majumdar, Sumit R; Mahon, Jeffrey L; Johnson, Jeffrey A

    2005-09-01

    Beta-blocker therapy has been proven to reduce mortality and reinfarction after myocardial infarction (MI), but the impact of beta-blockers on cardiac outcomes in patients with type 2 diabetes in routine practice is not clear. The purpose of this study was to determine the effectiveness of beta-blockers after MI in patients with type 2 diabetes. Using the Saskatchewan Health Databases, 12,272 patients with newly treated diabetes were identified between 1991 and 1996; 625 patients were subsequently admitted for MI. Beta-blocker exposure within 30 days of discharge was identified in 298 patients, and all were followed until death, coverage termination, or 31 December 1999. Multivariate proportional hazards models were used to assess differences in all-cause mortality, recurrent MI, and 30-day all-cause rehospitalization (the latter a proxy measure for drug safety). Patients were aged 69 +/- 11 years old, 66% were male, and mean follow-up was 2.7 +/- 2.1 years. Overall, beta-blockers were prescribed for 48% of patients. There were fewer deaths in the beta-blocker group versus control subjects (55 of 298 [18.5%] vs. 126 of 327 [38.5%], respectively, P beta-blockers were not associated with improved survival in multivariate analyses (hazard ratio [HR] 0.89 [95% CI 0.63-1.25]). There were no differences in rates of recurrent MI (adjusted HR 1.35 [0.93-1.95]) or rehospitalizations (adjusted odds ratio 1.40 [0.83-2.37]) between the groups. Beta-blocker therapy post-MI was not associated with reduced mortality or fewer recurrent events in people with type 2 diabetes in routine practice, although these medications were safe in this population.

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

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    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.

  12. 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...

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

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    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.

  14. Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[F-18]fluoromethyl-5-methyl-adamantane (F-18-MEM) : A potential radioligand for mapping the NMDA-receptor complex

    NARCIS (Netherlands)

    Samnick, S; Ametamey, S; Leenders, KL; Vontobel, P; Quack, G; Parsons, CG; Neu, H; Schubiger, PA

    The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane (F-19-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that F-19-MEM is a moderate NMDA receptor channel blocker. A procedure for

  15. AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease.

    Science.gov (United States)

    Liu, Tian-Jing; Shi, Yong-Yan; Wang, En-Bo; Zhu, Tong; Zhao, Qun

    2016-02-01

    Angiotensin II, which is the main effector of the renin‑angiotensin system, has an important role in intestinal inflammation via the angiotensin II type 1 receptor (AT1R). The present study aimed to investigate the protective effects of the AT1R blocker losartan on 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis. Losartan was administered to male adult C57BL/6 J mice 2 weeks prior to the induction of colitis, and images of the whole colon were captured to record changes, scored according to a microscopic scoring system, and reverse transcription-quantitative polymerase chain reaction were performed in order to investigate colonic inflammation. In addition, intestinal epithelial barrier permeability was evaluated, and intestinal epithelial cell (IEC) apoptosis was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and apoptosis-related protein expression levels were detected by western blotting. Losartan was able to attenuate TNBS-induced body weight loss and colonic damage. Furthermore, T helper 1-mediated proinflammatory cytokines were suppressed by losartan, and gut permeability was largely preserved. TUNEL staining revealed reduced IEC apoptosis in the losartan-treated mice. Losartan also increased the B-cell lymphoma 2 (Bcl2)/Bcl-2-associated X protein (Bax) ratio and suppressed caspase-3 induction. These results suggested that the AT1R blocker losartan may attenuate TNBS-induced colitis by inhibiting the apoptosis of IECs. The effects of losartan were partially mediated through increasing the Bcl-2/Bax ratio and subsequently suppressing the induction of the proapoptotic mediator caspase-3.

  16. Beta-blocker use and COPD mortality: a systematic review and meta-analysis

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    Etminan Mahyar

    2012-09-01

    Full Text Available Abstract Background Despite the benefits of beta-blockers in patients with established or sub-clinical coronary artery disease, their use in patients with chronic obstructive pulmonary disease (COPD has been controversial. Currently, no systematic review has examined the impact of beta-blockers on mortality in COPD. Methods We systematically searched electronic bibliographic databases including MEDLINE, EMBASE and Cochrane Library for clinical studies that examine the association between beta-blocker use and all cause mortality in patients with COPD. Risk ratios across studies were pooled using random effects models to estimate a pooled relative risk across studies. Publication bias was assessed using a funnel plot. Results Our search identified nine retrospective cohort studies that met the study inclusion criteria. The pooled relative risk of COPD related mortality secondary to beta-blocker use was 0.69 (95% CI: 0.62-0.78; I2=82%. Conclusion The results of this review are consistent with a protective effect of beta-blockers with respect to all cause mortality. Due to the observational nature of the included studies, the possibility of confounding that may have affected these results cannot be excluded. The hypothesis that beta blocker therapy might be of benefit in COPD needs to be evaluated in randomised controlled trials.

  17. Do beta-blockers alter dyspnea and fatigue in advanced lung cancer? A retrospective analysis.

    Science.gov (United States)

    Cameron, Paul; Ellis, Peter M; Pond, Gregory R; Goffin, John R

    2012-09-01

    Dyspnea is common in lung cancer and may be partially attributable to increased ventilatory drive due to muscle weakness. The sympathetic component of this pathway might be mitigated by β-blockers. A retrospective review of new patients with stage III-IV non-small lung cancer or any small cell lung cancer was undertaken to assess the impact of β-blocker use on dyspnea and fatigue. Data were abstracted for clinical characteristics, β-blocker use, and pre-treatment Edmonton Symptom Assessment System dyspnea and fatigue scores. Of 348 patients assessed, 202 met eligibility criteria. The median age was 67, 55.4% were female, 18.8% had chronic obstructive pulmonary disease (COPD), and 5.9% had active coronary artery disease. Over 60% of patients scored 4/10 or higher on their dyspnea and fatigue scores. While dyspnea and fatigue were moderately associated, no association was found between β-blocker use and either symptom. Recorded dosages of β-blockers were low. COPD was associated with dyspnea and fatigue, while anemia was associated with fatigue. Dyspnea and fatigue are prevalent and increased in the presence of COPD and anemia. No association between β-blocker use and dyspnea or fatigue scores was observed. This may be attributable to inadequate dosing or to retrospective bias.

  18. Are ACE Inhibitors and Beta-blockers Dangerous in Patients at Risk for Anaphylaxis?

    Science.gov (United States)

    Coop, Christopher A; Schapira, Rebecca S; Freeman, Theodore M

    The objective of this article is to review the available studies regarding angiotensin converting enzyme (ACE) inhibitors and beta-blockers and their effect on patients at risk for anaphylaxis. A literature search was conducted in PUBMED to identify peer-reviewed articles using the following keywords: anaphylaxis, ACE inhibitor, beta-blocker, food allergy, radiocontrast media, venom allergy, skin testing, and immunotherapy. Some studies show an increased risk of anaphylaxis in patients who are taking ACE inhibitors and beta-blockers, whereas others studies do not show an increased risk. For venom immunotherapy, there are more data supporting the concomitant use of beta-blockers and ACE inhibitors in the build-up and maintenance phases. Most of the medical literature is limited to case reports and retrospective data. Prospective controlled trials are needed on this important topic. For those patients at risk of anaphylaxis who lack cardiovascular disease, it is recommended to avoid beta-blockers and possibly ACE inhibitors. However, for those patients with cardiovascular disease, beta-blockers and ACE inhibitors have been shown to increase life expectancy. Consideration should be given for the concomitant use of these medications while patients are receiving venom immunotherapy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  19. 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.

  20. Ziconotide: neuronal calcium channel blocker for treating severe chronic pain.

    Science.gov (United States)

    Miljanich, G P

    2004-12-01

    Ziconotide (PRIALT) is a neuroactive peptide in the final stages of clinical development as a novel non-opioid treatment for severe chronic pain. It is the synthetic equivalent of omega-MVIIA, a component of the venom of the marine snail, Conus magus. The mechanism of action underlying ziconotide's therapeutic profile derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels (N-VSCCs). Direct blockade of N-VSCCs inhibits the activity of a subset of neurons, including pain-sensing primary nociceptors. This mechanism of action distinguishes ziconotide from all other analgesics, including opioid analgesics. In fact, ziconotide is potently anti-nociceptive in animal models of pain in which morphine exhibits poor anti-nociceptive activity. Moreover, in contrast to opiates, tolerance to ziconotide is not observed. Clinical studies of ziconotide in more than 2,000 patients reveal important correlations to ziconotide's non-clinical pharmacology. For example, ziconotide provides significant pain relief to severe chronic pain sufferers who have failed to obtain relief from opiate therapy and no evidence of tolerance to ziconotide is seen in these patients. Contingent on regulatory approval, ziconotide will be the first in a new class of neurological drugs: the N-type calcium channel blockers, or NCCBs. Its novel mechanism of action as a non-opioid analgesic suggests ziconotide has the potential to play a valuable role in treatment regimens for severe chronic pain. If approved for clinical use, ziconotide will further validate the neuroactive venom peptides as a source of new and useful medicines.

  1. Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD).

    Science.gov (United States)

    Duffy, Sean; Marron, Robert; Voelker, Helen; Albert, Richard; Connett, John; Bailey, William; Casaburi, Richard; Cooper, J Allen; Curtis, Jeffrey L; Dransfield, Mark; Han, MeiLan K; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando; Lazarus, Stephen; Niewoehner, Dennis; Scanlon, Paul D; Sciurba, Frank; Scharf, Steven; Reed, Robert M; Washko, George; Woodruff, Prescott; McEvoy, Charlene; Aaron, Shawn; Sin, Don; Criner, Gerard J

    2017-06-19

    Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts. We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use. Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time. We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

  2. Effect of L- type Calcium Channel Blocker Nimodipine and T-type Calcium Channel Blocker Flunarizine on Motor Control in Mice

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    Swapnil Balkrishna Kaikade

    2015-05-01

    Full Text Available Objective: To study the effect of L-type of Calcium channel blocker nimodipine and T-type of calcium channel blocker funarizine on locomotor activity in mice without pretreatment by any other drug. Materials and method: The study was carried out following permission from the Institutional animal ethics committee. Healthy Swiss albino mice of either sex were selected by the strict inclusion and exclusion criteria and the grouping is done. Group A is control treated with normal saline, Group B and C received two titrated doses of nimodipine while Group D and E received two titrated doses of flunarizine. The animals were then observed for motor control on inclined plane and the Statistical analysis was done by using unpaired‘t’ test. Results: L-type calcium channel blocker nimodipine has dose dependent effect on motor control on inclined plane while the T- type calcium channel blocker flunarizine has no effect on motor control. Conclusion: Nimodipine has significant dose dependent depressant action on motor control on inclined plane while flunarizine has no effect on the above mentioned parameter.

  3. Statin, calcium channel blocker and Beta blocker therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes.

    Science.gov (United States)

    Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Chang, Hsiu-Ling; Yang, Yi-Hsin; Hsiao, Pi-Jung; Shin, Shyi-Jang

    2015-05-18

    It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD) in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58-0.98), 0.72 (95% CI, 0.58-0.91) and 0.76 (95% CI, 0.60-0.97), respectively. Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes.

  4. Statin, Calcium Channel Blocker and Beta Blocker Therapy May Decrease the Incidence of Tuberculosis Infection in Elderly Taiwanese Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Mei-Yueh Lee

    2015-05-01

    Full Text Available Background: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. Methods: A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. Results: After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58–0.98, 0.72 (95% CI, 0.58–0.91 and 0.76 (95% CI, 0.60–0.97, respectively. Conclusion: Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes.

  5. Differential Effects in Cardiovascular Markers between High-Dose Angiotensin II Receptor Blocker Monotherapy and Combination Therapy of ARB with Calcium Channel Blocker in Hypertension (DEAR Trial

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    Kenichiro Kinouchi

    2011-01-01

    Full Text Available Background/Aims. Arterial stiffness is an independent risk factor for cardiovascular morbidity and mortality. This study was conducted to determine the effect of olmesartan (OLM and azelnidipine (AZL on arterial stiffness using the cardio-ankle vascular index (CAVI, which is a novel blood pressure (BP-independent marker for arterial stiffness in hypertensive patients. Methods. Fifty-two consecutive hypertensive patients were randomly assigned either to a group treated with OLM monotherapy or to a group treated with OLM and AZL combination therapy. Clinical and biological parameters were measured before and 12 months after the start of this study. Results. Both therapies significantly and similarly reduced BP, augmentation index, and plasma aldosterone levels. The combination therapy significantly decreased CAVI and serum low-density lipoprotein (LDL-C levels and these reductions were significantly greater than those produced with monotherapy. No significant differences in metabolic parameters were observed between the two therapies. Conclusion. The combination therapy with OLM and AZL had beneficial effects on arterial stiffness assessed by CAVI, LDL-C, and metabolism, despite the similar BP reduction, compared with OLM monotherapy. Since these markers are known to influence the future risk of cardiovascular events, combination therapy with OLM and AZL could be a useful choice for treating hypertensive patients.

  6. Drug treatment rates with beta-blockers and ACE-inhibitors/angiotensin receptor blockers and recurrences in takotsubo cardiomyopathy: A meta-regression analysis.

    Science.gov (United States)

    Brunetti, Natale Daniele; Santoro, Francesco; De Gennaro, Luisa; Correale, Michele; Gaglione, Antonio; Di Biase, Matteo

    2016-07-01

    In a recent paper Singh et al. analyzed the effect of drug treatment on recurrence of takotsubo cardiomyopathy (TTC) in a comprehensive meta-analysis. The study found that recurrence rates were independent of clinic utilization of BB prescription, but inversely correlated with ACEi/ARB prescription: authors therefore conclude that ACEi/ARB rather than BB may reduce risk of recurrence. We aimed to re-analyze data reported in the study, now weighted for populations' size, in a meta-regression analysis. After multiple meta-regression analysis, we found a significant regression between rates of prescription of ACEi and rates of recurrence of TTC; regression was not statistically significant for BBs. On the bases of our re-analysis, we confirm that rates of recurrence of TTC are lower in populations of patients with higher rates of treatment with ACEi/ARB. That could not necessarily imply that ACEi may prevent recurrence of TTC, but barely that, for example, rates of recurrence are lower in cohorts more compliant with therapy or more prescribed with ACEi because more carefully followed. Randomized prospective studies are surely warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. COMBINATION OF DIRECT RENNIN INHIBITOR - ALISKIREN, ANGIOTENSIN II RECEPTOR BLOCKER - VALSARTAN, AND CALCIUM CHANNEL BLOCKER - AMLODIPINE, IN THERAPY OF HYPERTENSIVE PATIENT WITH GOUT (CASE REPORT

    Directory of Open Access Journals (Sweden)

    O. V. Dralova

    2011-01-01

    Full Text Available Pharmacotherapy optimization in patients with arterial hypertension and gout is very important. Achievement of the target blood pressure levels is possible with the use of combinations of effective antihypertensive drugs with neutral metabolic profile and safety, in particular a combination of valsartan, amlodipine and aliskiren. Clinical case of this combination use in patient with arterial hypertension and gout is presented.

  8. Implication of different initial beta blockers on treatment persistence: atenolol vs new-generation beta blocker, a population-based study.

    Science.gov (United States)

    Choi, Yun Jung; Ah, Young-Mi; Kong, Jisun; Choi, Kyung Hee; Kim, Baegeum; Han, Nayoung; Yu, Yun Mi; Oh, Jung Mi; Shin, Wan Gyoon; Lee, Hae-Young; Lee, Ju-Yeun

    2016-08-01

    Potential heterogeneity within the same class of drug in terms of persistence may lead to different clinical implications. Given that the increased risks of mortality and cardiovascular events are due, in part, to the lack of persistent use of antihypertensive medications, the objective of this study was to evaluate 1-year persistence of new-generation beta blockers compared to atenolol in antihypertensive treatment-naïve patients. A total of 9978 patients aged 18 years or older with hypertension newly diagnosed in 2012, without hypertension-related complication and initiated treatment with beta blocker monotherapy during 2012 were included in the analysis. Rate and duration of treatment and drug persistence were compared between atenolol and new-generation beta blockers. Hazards of discontinuation in nonatenolol compared to atenolol were evaluated using a multivariate Cox proportional model. The rate of treatment persistence was higher in the nonatenolol group (57.35% vs 53.40%, PNew-generation beta blockers demonstrated a lower risk of treatment discontinuation (HR: 0.91, 95% CI: 0.86-0.96) compared to atenolol; a notable improvement was observed with carvedilol and nebivolol (HR: 0.74, 95% CI: 0.69-0.80 and HR: 0.79, 95% CI: 0.70-0.89, respectively), whereas betaxolol showed a substantially greater hazard for discontinuation compared to atenolol. This study demonstrated a meaningful improvement in treatment persistence with new-generation beta blockers compared to atenolol, with betaxolol as exception. © 2016 John Wiley & Sons Ltd.

  9. Beta-blockers may reduce intrusive thoughts in newly diagnosed cancer patients.

    Science.gov (United States)

    Lindgren, Monica E; Fagundes, Christopher P; Alfano, Catherine M; Povoski, Stephen P; Agnese, Doreen M; Arnold, Mark W; Farrar, William B; Yee, Lisa D; Carson, William E; Schmidt, Carl R; Kiecolt-Glaser, Janice K

    2013-08-01

    A cancer diagnosis provokes significant levels of emotional distress, with intrusive thoughts being the most common manifestation among breast cancer survivors. Cancer-related intrusive thoughts can take the form of emotional memories, flashbacks, nightmares, and intrusive images. Emotional arousal after a severe life stressor prolongs adrenergic activation, which in turn may increase risk for post-traumatic symptomatology. However, antihypertensive beta-blockers block adrenergic activation and are known to reduce traumatic memories and related psychological distress. Thus, the current study examined the association between beta-blocker use and the severity of cancer-related intrusive thoughts and related symptoms following a cancer diagnosis. The 174 breast and 36 female colorectal cancer patients who had recently undergone diagnostic screening or biopsy included 39 beta-blocker users and 171 non-users. Prior to any cancer treatment including surgery, participants completed questionnaires that included the Impact of Events Scale and the Center for Epidemiological Studies Depression Scale. Analyses controlled for age, education, cancer stage, cancer type, days since diagnosis, marital status, depression, and comorbidities. Although the high rates of cancer-related distress in this sample were similar to those of other studies with recently diagnosed patients, beta-blocker users endorsed 32% fewer cancer-related intrusive thoughts than non-users. Recently diagnosed cancer patients using beta-blockers reported less cancer-related psychological distress. These results suggest that beta-blocker use may benefit cancer patients' psychological adjustment following diagnosis, and provide a promising direction for future investigations on the pharmacological benefits of beta-blockers for cancer-related distress. Copyright © 2012 John Wiley & Sons, Ltd.

  10. BETA-BLOCKERS AND RENOPROTECTION: THE POTENTIAL OF CARVEDILOL

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    I. T. Murkamilov

    2017-01-01

    Full Text Available The review presented the importance of carvedilol using in terms of renoprotection in renal dysfunction at the pre-dialysis stage of the disease in order to reduce the risk of progression of chronic kidney diseases (CKD and the development of cardiovascular complications. Immune and non-immune mechanisms (proteinuria, dyslipidemia, anemia, arterial hypertension of renal dysfunction progression in patients with CKD of inflammatory and non-inflammatory origin are described. Moreover, with the slowing down of the glomerular filtration rate in CKD, the role of non-immunefactors in the development of cardiovascular complications becomes very important. In contrast to non-selective and some β1-selective beta-blockers, the use of beta-adenoblocker with vasodilating activity, in particular carvedilol, makes it possible to prevent the onset of the terminal stage ofCKD. Carvedilol, being a lipophilic beta-adrenoblocker of the third generation with alpha-blocking properties, influences the possible mechanismsof renoprotection: antihypertensive (including in combined antihypertensive therapy, anti-inflammatory, antiproliferative, anti-apoptotic, antioxidant, antiplatelet and others. Carvedilol due to the vasodilating effect softens the stress of the parietal shear, exerting a retarding action on theprogression of CKD. Carvedilol with a pronounced vasodilating effect and a long half-life significantly reduces central arterial pressure that is also animportant renoprotective mechanism in the treatment of patients with renal dysfunction. Carvedilol has an important renoprotective mechanism in CKD – inhibition of the secretion of the potent vasoconstrictor endothelin. In the metabolic syndrome, in which there is a significant risk of developing renal dysfunction, carvedilol levels the imbalance of adipokine secretion, insulin resistance, sodium and water retention, and the activation of renin-angiotensin-aldosterone and sympathoadrenal systems. Carvedilol at

  11. Development of a population pharmacokinetic model to predict brain distribution and dopamine D2 receptor occupancy of raclopride in nonanesthetized rat

    NARCIS (Netherlands)

    Wong, Y.C.; Ilz, aut ikkova T.I.; Wijk, van R.C.; Hartman, R.J.; Lange, de E.C.M.

    2018-01-01

    BACKGROUND: Raclopride is a selective antagonist of the dopamine D2 receptor. It is one of the most frequently used in vivo D2 tracers (at low doses) for assessing drug-induced receptor occupancy (RO) in animals and humans. It is also commonly used as a pharmacological blocker (at high doses) to

  12. Intensive Glycemic Therapy in Patients With Type 2 Diabetes on β-Blockers.

    Science.gov (United States)

    Tsujimoto, Tetsuro; Sugiyama, Takehiro; Noda, Mitsuhiko; Kajio, Hiroshi

    2016-10-01

    Recent studies have suggested that β-blockers may decrease the adverse influence of hypoglycemia and reduce hypoglycemia-associated cardiac arrhythmias and death. We evaluated whether intensive glycemic therapy in patients with diabetes receiving treatment with β-blockers showed beneficial effects for the prevention of cardiovascular events without increased mortality compared with a standard glycemic therapy. We used Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial data to assess the risks of cardiovascular events, all-cause death, and cardiovascular death in patients with diabetes receiving treatment with β-blockers (n = 3,079) and not receiving treatment with β-blockers (n = 7,145) using Cox proportional hazard models. In patients receiving treatment with β-blockers, the cumulative event rates for cardiovascular events were significantly lower in the intensive therapy group compared with the standard therapy group (hazard ratio [HR] 0.81; 95% CI 0.67-0.97; P = 0.02), whereas those rates in patients not receiving treatment with β-blockers were not significantly different (HR 0.92; 95% CI 0.78-1.09; P = 0.36). Conversely, the cumulative event rates for all-cause and cardiovascular deaths in patients receiving treatment with β-blockers were not significantly different between the standard therapy and intensive therapy groups (all-cause death: HR 1.08; 95% CI 0.83-1.42; P = 0.54; cardiovascular death: HR 1.05; 95% CI 0.72-1.51; P = 0.79), whereas in patients not receiving treatment with β-blockers, the event rates were significantly higher in the intensive therapy group compared with the standard therapy group (all-cause death: HR 1.25; 95% CI 1.02-1.52; P = 0.02; cardiovascular death: HR 1.43; 95% CI 1.03-1.98; P = 0.03). Intensive glycemic therapy may be effective in patients with type 2 diabetes receiving treatment with β-blockers. © 2016 by the American Diabetes Association.

  13. A genetic variant in the catechol-O-methyl transferase (COMT) gene is related to age-dependent differences in the therapeutic effect of calcium-channel blockers.

    Science.gov (United States)

    Xu, Jiayue; Boström, Adrian E; Saeed, Mohamed; Dubey, Raghvendra K; Waeber, Gérard; Vollenweider, Peter; Marques-Vidal, Pedro; Mwinyi, Jessica; Schiöth, Helgi B

    2017-07-01

    Hypertension is the leading risk factor for cardiovascular disease and one of the major health concerns worldwide. Genetic factors impact both the risk for hypertension and the therapeutic effect of antihypertensive drugs. Sex- and age-specific variances in the prevalence of hypertension are partly induced by estrogen. We investigated 6 single nucleotide polymorphisms in genes encoding enzymes involved in estrogen metabolism in relation to sex- and age-specific differences in the systolic and diastolic blood pressure (SBP and DBP) outcome under the treatment of diuretics, calcium-channel blockers (CCBs), angiotensin-converting-enzyme inhibitors, and angiotensin-receptor blockers (ARBs).We included 5064 subjects (age: 40-82) from the population-based CoLaus cohort. Participants were genotyped for the catechol-O-methyltransferase gene (COMT) variants rs4680, rs737865, and rs165599; the uridine-diphospho-glucuronosyltransferase 1A gene family (UGT1A) variants rs2070959 and rs887829; and the aromatase gene (CYP19A1) variant rs10046. Binomial and linear regression analyses were performed correcting for age, sex, body mass index, smoking, diabetes, and antihypertensive therapy to test whether the variants in focus are significantly associated with BP.All investigated COMT variants were strongly associated with the effect of diuretics, CCBs, and ARBs on SBP or DBP (P individuals (age ≥ 70) alone (Δ = -14.08 mm Hg, P = .0005).These results underline the important role of estrogens and catecholamines in hypertension and the importance of genotype dependent, age-related adjustments of calcium-channel blocker treatment.

  14. 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...... myocardial infarction trials, a significant interaction (Pinteraction=0.02) was noted such that â-blockers reduced mortality in the pre-reperfusion[Incident Rate Ratio (IRR)=0.86, 95% CI 0.79-0.94] but not in the reperfusion era(IRR=0.98, 95% CI 0.92-1.05). In the pre-reperfusion era, â-blockers reduced...... cardiovascular mortality(IRR=0.87, 95% CI 0.78-0.98), myocardial infarction(IRR=0.78, 95% CI 0.62-0.97), and angina(IRR=0.88, 95% CI 0.82-0.95) with no difference for other outcomes. In the reperfusion era, â-blockers reduced myocardial infarction(IRR=0.72, 95% CI 0.62-0.83) (NNTB=209) and angina(IRR=0.80, 95...

  15. Photodegradation of selected β-blockers in aqueous fulvic acid solutions: kinetics, mechanism, and product analysis.

    Science.gov (United States)

    Chen, Yong; Li, Hong; Wang, Zongping; Li, Huijie; Tao, Tao; Zuo, Yuegang

    2012-06-01

    The photodegradation of the widely used β-blockers atenolol and metoprolol were investigated in the presence of fulvic acid (FA) under simulated sunlight. Both atenolol and metoprolol undergo indirect photodegradation in the FA solutions. The triplet excited state of FA ((3)FA(∗)) was verified to be main reactive species responsible for the photosensitized degradation of β-blockers. An electron transfer mechanism for the interaction between β-blockers and (3)FA(∗) was proposed on the basis of a series of experiments. Magnetic property of metal ions exhibited significant impact on photosensitized degradation. Diamagnetic metal ions such as Mg(2+), Ca(2+), Zn(2+), and Al(3+) negligibly affected the degradation. In contrast, paramagnetic metal ions including Mn(2+), Cu(2+), Fe(3+), and Cr(3+) markedly inhibited the reactions in the order of Cr(3+) < Fe(3+) < Cu(2+) < Mn(2+). The inhibition was related to the complexation ability with FA. By LC-ESI-MS/MS analysis, deisopropyl-atenolol (metoprolol) was identified as the main photosensitized product. The degradation pathways of β-blockers involving electron transfer processes were proposed. This finding strongly suggests that (3)FA(∗) was important reactive species for the degradation of β-blockers in natural waters. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. 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.

  17. 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

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

    Science.gov (United States)

    McGill, Janet B

    2010-06-01

    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. beta-blockers are playing an increasingly important role in the management of hypertension in high-risk patients. beta-blockers are a heterogeneous class of agents, and this review presents the differences between beta-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 beta-blockers are only effective if patients adhere to medication treatment long term. beta-blockers with proven efficacy, once-daily dosing, and lower side effect profiles may become instrumental in the treatment of hypertensive diabetic and nondiabetic patients.

  19. The role of vasodilating beta-blockers in patients with hypertension and the cardiometabolic syndrome.

    Science.gov (United States)

    Taylor, Addison A; Bakris, George L

    2010-07-01

    In the United States, a vast segment of the adult population is classified as having the cardiometabolic syndrome, and currently there are epidemic rates of both type 2 diabetes mellitus and obesity. Hypertension is closely linked with these metabolic disorders and is a strong independent predictor of incident type 2 diabetes. In addition, hypertension is an important contributor to increasing cardiovascular disease risk in patients with the cardiometabolic syndrome. Lowering elevated blood pressure in patients with the cardiometabolic syndrome or diabetes is a critical component of reducing global cardiovascular risk. However, aggressive management of hypertension in these patients is often challenging, and the presence of these conditions is associated with poor blood pressure control. The utility of beta-blockers in patients with these conditions continues to be a subject of intense debate, given the adverse metabolic effects associated with conventional beta-blockers. Data on vasodilating beta-blockers, however, suggest that these agents have favorable or neutral metabolic effects and generally more favorable effects when compared with nonvasodilating members of this class. These agents may expand the utility of beta-blockers to patient populations traditionally considered not to be optimal candidates for beta-blocker therapy-a fact which has important clinical implications, because more antihypertensive agents are needed to diversify the therapeutic options available for clinicians treating hypertension in patients with the cardiometabolic syndrome or type 2 diabetes. Copyright (c) 2010. Published by Elsevier Inc.

  20. The COX-2 Selective Blocker Etodolac Inhibits TNFα-Induced Apoptosis in Isolated Rabbit Articular Chondrocytes

    Directory of Open Access Journals (Sweden)

    Hiroshi Matsuura

    2013-09-01

    Full Text Available Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA. Recently, we reported that activation of volume-sensitive Cl− current (ICl,vol mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of ICl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNFα resulted in an obvious increase in membrane Cl− conductance. The TNFα-evoked Cl− current exhibited electrophysiological and pharmacological properties similar to those of ICl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited ICl,vol activation by TNFα as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNFα. Thus, the COX-2-selective blocker had an inhibitory effect on TNFα-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA.

  1. Do β-Blockers Decrease the Hypermetabolic State in Critically Ill Children With Severe Burns?

    Science.gov (United States)

    Shan Chew, Elaine Chu; Baier, Nicole; Lee, Jan Hau

    2015-08-01

    Severe burns result in a hypermetabolic state that is associated with increased morbidity and mortality. We reviewed the literature to determine if there is strong evidence that short-term β-blockers reduce the hypermetabolic state or mortality and length of stay (LOS) compared with no therapy in patients with severe burns. A literature search of PubMed, Embase, the Cochrane Database of Systematic Reviews, and BestBETs was conducted on the use of adrenergic β-antagonists in burn patients. Six randomized controlled trials met the inclusion criteria. Five pediatric trials found that β-blockers reduced the hypermetabolic state (as defined by reduction of cardiac work, rate pressure product, resting energy expenditure, central deposition of fat, and bone mineral loss) and were associated with an improvement in lean muscle mass in patients wi