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Sample records for angiotensin-receptor blocker telmisartan

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

    DEFF Research Database (Denmark)

    NN, NN; Yusuf, S; Teo, K;

    2008-01-01

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

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

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    Yuki Hamano

    2011-09-01

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

  3. 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

  4. Angiotensin receptor blockers in diabetic nephropathy

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    Parving, Hans-Henrik; Andersen, Steen; Jacobsen, Peter

    2004-01-01

    The activity of the renin-angiotensin-aldosterone system (RAAS) is elevated both in the circulation and in the renal tissue of diabetic and nondiabetic nephropathies. The increased RAAS activity plays an important role in the hemodynamic and nonhemodynamic pathogenetic mechanisms involved in kidney...... with diabetic nephropathy have demonstrated that angiotensin II receptor blockers (ARB) induce favorable changes in systemic blood pressure, renal hemodynamics, and proteinuria similar to those induced by angiotensin-converting enzyme (ACE) inhibition. Studies have revealed the optimal renoprotective dose...... in diabetic nephropathy. In addition, dual RAAS blockade is safe and well tolerated. Impaired autoregulation of glomerular filtration rate (GFR); demonstrated with some blood pressure-lowering agents implies disturbances in the downstream transmission of the systemic blood pressure into the glomerulus...

  5. 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.

  6. Angiotensin-receptor blockers as therapy for mildto- moderate hypertension-associated non-alcoholic steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Eugen Florin Georgescu; Reanina Ionescu; Mihaela Niculescu; Laurentiu Mogoanta; Liliana Vancica

    2009-01-01

    AIM: To evaluate insulin resistance, cytolysis and nonalcoholic steatohepatitis (NASH) score (NAS) using the Kleiner and Brunt criteria in 54 patients with NASH and mild-to-moderate hypertension, treated with telmisartan vs valsartan for 20 mo. METHODS: All patients met the NCEP-ATP Ⅲ criteria for metabolic syndrome. Histology confirmed steatohepatitis, defined as a NAS greater than five up to 3 wk prior inclusion, using the current criteria. Patients with viral hepatitis, chronic alcohol intake, drug abuse or other significant immune or metabolic hepatic pathology were excluded. Subjects were randomly as -signed either to the valsartan (V) group (standard dose 80 mg o.d., n = 26), or to the telmisartan (T) group (standard dose 20 mg o.d., n = 28). Treatment had to be taken daily at the same hour with no concomitant medication or alcohol consumption allowed. Neither the patient nor the medical staff was aware of treatment group allocation. Paired liver biopsies obtained at inclusion (visit 1) and end of treatment (EOT) were assessed by a single blinded pathologist, not aware of patient or treatment group. Blood pressure, BMI, ALT, AST, HOMA-IR, plasma triglycerides (TG) and total cholesterol (TC) were evaluated at inclusion and every 4 mo until EOT (visit 6). RESULTS: At EOT we noticed a significant decrease in ALT levels vs inclusion in all patients and this decrease did not differ significantly in group T vs group V. HOMA-IR significantly decreased at EOT vs inclusion in all patients but in group T, the mean HOMA-IR decrease per month was higher than in group V. NAS significantly diminished at EOT in all patients with a higher decrease in group T vs group V. CONCLUSION: Angiotensin receptor blockers seem to be efficient in hypertension-associated NASH. Telmisartan showed a higher efficacy regarding insulin resistance and histology, perhaps because of its specific PPAR-gamma ligand effect.

  7. 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.

  8. 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

  9. 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

    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 th

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

    NARCIS (Netherlands)

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

    2016-01-01

    BACKGROUND: 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

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

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    Georg Nickenig

    2006-03-01

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

  12. 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

    blood pressure. METHODS: Participants in this randomised, placebo-controlled, double-blind trial were recruited from 146 centres in nine north European countries. Patients older than 18 years with acute stroke (ischaemic or haemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included......%) patients taking candesartan and 13 (1%) allocated placebo. INTERPRETATION: There was no indication that careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. If anything, the evidence suggested...

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

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    Lee Robert E

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis...... of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin-angiotensin-aldosterone system (non-RAASi)-based antihypertensive therapy. Treatment effects on renal and cardiovascular outcomes were compared in subgroups based on dietary sodium intake...... effects of ARB compared with non-RAASi-based therapy on renal and cardiovascular outcomes were greater in patients with type 2 diabetic nephropathy with lower than higher dietary sodium intake. This underscores the avoidance of excessive sodium intake, particularly in type 2 diabetic patients receiving...

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

    Science.gov (United States)

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

    2012-08-01

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

  16. Rationale for combination therapy in hypertension management: focus on angiotensin receptor blockers and thiazide diuretics.

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    Nash, David T

    2007-04-01

    Despite recognition that hypertension is a major risk factor for cardiovascular events and mortality, blood pressure control rates remain low in the US population. Reflecting clinical trial results, hypertension management guidelines assert the clinical benefit of achieving current blood pressure goals and indicate that most patients will require 2 or more drugs to reach goal. Well-designed drug combinations counter hypertension via complementary mechanisms that increase antihypertensive efficacy, potentially with lower rates of adverse events than higher dose monotherapy regimens. Lower adverse event rates, in turn, may contribute to greater adherence with treatment. The combination of a low-dose diuretic with agents that block the effects of the renin-angiotensin system (RAS), such as angiotensin receptor blockers, has been found in numerous clinical trials to be highly effective for lowering blood pressure in patients with uncomplicated as well as high-risk hypertension, with a comparable favorable side effect profile compared with monotherapy. Moreover, agents that block the RAS are associated with a lower risk of new-onset diabetes mellitus than other antihypertensive classes. Complementary combinations of antihypertensive agents provide an efficient and effective approach to hypertension management.

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

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    Laurent Azoulay

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

  18. Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

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    Raebel, Marsha A

    2012-06-01

    The aims of this article are to review the current understanding of hyperkalemia associated with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy. This includes reviewing the pathophysiology of how these agents affect potassium handling within the kidney, risk factors for developing hyperkalemia, incidence, clinical signs and symptoms, and providing a practical approach to treatment of the patient who is either at risk of, or experiencing, hyperkalemia. ACEi and ARB are effective therapeutic agents used in a variety of clinical scenarios. However, related to their effects on the renin-angiotensin-aldosterone system, their use can be associated with hyperkalemia, particularly in patients who have chronic renal insufficiency. Published incidence estimates of hyperkalemia associated with ACEi or ARB vary, but up to 10% of patients may experience at least mild hyperkalemia. Important considerations when initiating ACEi or ARB therapy include obtaining an estimate of glomerular filtration rate and a baseline serum potassium concentration, as well as assessing whether the patient has excessive potassium intake from diet, supplements, or drugs that can also increase serum potassium. Serum potassium monitoring shortly after initiation of therapy can assist in preventing hyperkalemia. If hyperkalemia does develop, prompt recognition of cardiac dysrhythmias and effective treatment to antagonize the cardiac effects of potassium, redistribute potassium into cells, and remove excess potassium from the body is important.Understanding the mechanism of action of ACEi and ARB coupled with judicious drug use and clinical vigilance can minimize the risk to the patient of developing hyperkalemia. Should hyperkalemia occur, prompt recognition and management can optimize clinical outcome.

  19. Calcium Channel Blockers, More than Diuretics, Enhance Vascular Protective Effects of Angiotensin Receptor Blockers in Salt-Loaded Hypertensive Rats

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    Yamamoto, Eiichiro; Kataoka, Keiichiro; Dong, Yi-Fei; Koibuchi, Nobutaka; Toyama, Kensuke; Sueta, Daisuke; Katayama, Tetsuji; Yasuda, Osamu; Ogawa, Hisao; Kim-Mitsuyama, Shokei

    2012-01-01

    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. PMID:22720058

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

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    Eiichiro Yamamoto

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

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

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    Bisognano, John D; McLaughlin, Trent; Roberts, Craig S; Tang, Simon SK

    2007-01-01

    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. PMID:18078009

  2. 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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    AIMS: Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation...... integrative discrimination index (RIDI). RESULTS: SBP response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses....... CONCLUSIONS: In this post hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate...

  4. Safety and efficacy of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in chronic allograft injury

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    P R Shah

    2011-01-01

    Full Text Available Angiotensin II plays a crucial role in the development of chronic allograft injury (CAI. Clinical experience with angiotensin converting enzyme inhibitor (ACEI and angiotensin receptor blockade (ARBS in CAI has unfortunately been limited. We carried out a prospective one year single center case controlled study to analyze the effect of ACEI /ARBS on the progression of CAI and in decreasing proteinuria. One hundred patients with CAI were evaluated. Of the 100 patients, 50 were selected to receive ACEI/ ARBS (group 1 and 50 managed without ACEI/ARBS (group 2. Their remaining management was similar in both the groups. Patients with hyperkalemia, history of allergic reactions, ACEI/ARBS intake and pregnancy were excluded. Average time for development of CAI was 19.6 ± 12.7 months in group 1 vs. 20.8 ± 12.8 in group 2. In group 1, mean systolic/diastolic BP was 136/82 mmHg at the time of establishment of CAI and 124/76 mmHg at the end of one year, and in group 2, it was 138/86 mmHg vs. 126/80 mmHg, respectively. Mean glomerular filtration rate (GFR was 48.78 ± 13.4 in the former vs. 44.23 ± 8.14 in the latter. ACEI/ARBS administration was associated with stabilization of serum creatinine. GFR was maintained up to one year after CAI. Group 1 had a decrease in proteinuria by 1.41 g/day as compared with group 2 with proteinuria of 0.83 g/day. ACEI/ARBS administration is beneficial in CAI for BP control and significant decrease in proteinuria along with the stabilization of graft function.

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

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    Ibrahim F. Benter

    2013-01-01

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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-08

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

  9. 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

  10. Patients With Newly Diagnosed Hypertension Treated With the Renin Angiotensin Receptor Blocker Azilsartan Medoxomil vs Angiotensin-Converting Enzyme Inhibitors: The Prospective EARLY Registry.

    Science.gov (United States)

    Schmieder, Roland E; Potthoff, Sebastian A; Bramlage, Peter; Baumgart, Peter; Mahfoud, Felix; Buhck, Hartmut; Ouarrak, Taoufik; Ehmen, Martina; Senges, Jochen; Gitt, Anselm K

    2015-12-01

    For patients with newly diagnosed hypertension, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are usually the first-line therapies. There is, however, no real-life data regarding the relative clinical effectiveness and tolerability of either drug class. The prospective registry, Treatment With Azilsartan Compared to ACE Inhibitors in Antihypertensive Therapy (EARLY), was conducted to evaluate the effectiveness of the ARB azilsartan medoxomil (AZL-M) vs ACE inhibitors in real-world patients. Of the 1153 patients with newly diagnosed hypertension who were included in the registry, 789 were prescribed AZL-M and 364 were prescribed an ACE inhibitor. After multivariate adjustment, AZL-M was found to provide superior blood pressure reduction and better target blood pressure (<140/90 mm Hg) achievement. The proportion of patients with adverse events was not statistically different between groups. The authors conclude that in newly diagnosed hypertensive patients, AZL-M provides superior blood pressure control with a similar safety profile compared with ACE inhibitors.

  11. [Effects of the combination of angiotensin receptor blockers and thiazide diuretics on laboratory values (levels of serum potassium, sodium, and uric acid)].

    Science.gov (United States)

    Takahashi, Tatsuya; Teramachi, Hitomi; Tachi, Tomoya; Noguchi, Yoshihiro; Nagasawa, Hiroyuki; Mizui, Takashi; Goto, Chitoshi; Tsuchiya, Teruo

    2014-01-01

    The combination of angiotensin receptor blockers (ARB) and a thiazide diuretic (hereafter, ARB/diuretic) is expected to improve patient adherence and increase the therapeutic effects because of the lower number of pills that require to be administered. In addition, an ARB/diuretic combination alleviates hypokalemia that frequently develops in patients receiving thiazide diuretics. In this study, we used electronic medical records to investigate the laboratory values (serum levels of potassium, sodium, and uric acid) of 194 ambulatory and hospitalized patients at the Gifu Municipal Hospital who received ARB/diuretic combination therapy for the first time between February 2010 and September 2012. According to the grade of classification of low serum potassium and sodium levels, the serum potassium level in one patient was grade 3 and the serum sodium level in two patients was grade 3 after the initiation of ARB/diuretic combination therapy. After administration of ARB/diuretic combination therapy, two patients received potassium supplements because their serum potassium levels decreased below the reference value. Similarly, one patient received a sodium supplement because of a decrease in the sodium level below the reference value. Uric acid level increased above the reference value after administration of the ARB/diuretic combination therapy in one patient; thus, this patient received antihyperuricemic agents. Therefore, pharmacists must carefully monitor the serum levels of potassium, sodium, and uric acid, particularly in the first six months after the initiation of ARB/diuretic combination therapy.

  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

    Background 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. Methods We randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to <30 mg/g of albumin-to-creatinine ratio) or microalbuminuria (30 to <300 mg/g) to the DRI group or ARB group (any ARB) with a target blood pressure of <130/80 mmHg. The primary endpoint was a reduction in albuminuria. Results 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. Conclusion 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. PMID:28033332

  13. Losartan/Hydrochlorothiazide Combination Therapy Surpasses High-dose Angiotensin Receptor Blocker in the Reduction of Morning Home Blood Pressure in Patients with Morning Hypertension

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    Nakamura,Yoshio

    2012-12-01

    Full Text Available Angiotensin receptor blockers (ARBs are the first-line antihypertensive agents. In clinical practice, it is often difficult to achieve the recommended blood pressure level by ARBs in their ordinal dosages alone. This study examined the practical efficacy of a combination therapy of ARB with thiazide diuretics for lowering morning home blood pressure (MHBP in comparison to high-dose ARB therapy in patients with morning hypertension administered an ordinal dosage of ARB. This study was performed in a prospective, randomized, open-labeled and blind-endpoint fashion. Patients were considered to have morning hypertension when their self-measured systolic MHBPs were 135mmHg or higher, irrespective of their diastolic MHBP and office blood pressures (OBPs. Forty-eight outpatients with morning hypertension receiving the ordinal dosage of ARB were given either losartan/hydrochlorothiazide (n=26 or high-dose ARB (n=22 in place of their previously prescribed ARB. No change in any medication was permitted during this period. Decreases of both systolic and diastolic MHBP after 3 months of treatment were significantly greater in the losartan/hydrochlorothiazide group than in the high-dose ARB group (p<0.05, respectively. The ratio of adverse events was somewhat high (23.1% in the losartan/hydrochlorothiazide group, 9.1% in the high-dose ARB group, respectively. However, there were no significant differences in any particular adverse event between groups. This study suggested losartan/hydrochlorothiazide might be superior to high-dose ARB for reducing morning home blood pressure.

  14. 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.

  15. 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

    2013-01-01

    Objectives 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. Design Retrospective cohort study using nested case-control analysis. Setting General practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. Participants A cohort of 487 372 users of antihypertensive drugs. Main outcome measures 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. Results 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). Conclusions 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. PMID:23299844

  16. 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

  17. Effect of angiotensin receptor blockers in the prevention of type 2 diabetes and cardiovascular events: a meta-analysis of randomized trials

    Institute of Scientific and Technical Information of China (English)

    SONG Hui-fen; WANG Su; LI Hong-wei

    2012-01-01

    Background As the incidence of type 2 diabetes is rapidly increasing,prevention of the disease should be considered as a crucial objective in the near future.Several studies have shown angiotensin receptor blockers (ARBs) may contribute to the prevention of new-onset type 2 diabetes.This study was conducted to determine if ARBs as monotherapy or combination therapy may experience a decreased incidence of new-onset type 2 diabetes and prevent cardiovascular events.Methods Relevant experimental and clinical studies were identified by searching MEDLINE (1969 to May 30,2011) to extract a consensus of trial data involving the effect of ARBs on prevention of new-onset type 2 diabetes and cardiovascular events.Studies were included if they were randomized controlled trials versus placebo/routine therapy.A random-effects model was utilized.Subgroup and sensitivity analyses were conducted.Results Eleven trials were identified,including 82738 patients.ARBs prevented new-onset type 2 diabetes (odds ratio 0.8 (95% CI 0.76,0.85)).Regardless of indication for use,essential hypertension (seven trials),impaired glucose tolerance (one trial),cardiocerebrovascular disease (two trials) or heart failure (one trial),reductions in new-onset type 2 diabetes were maintained (0.75 (0.69,0.82),0.85 (0.78,0.92),0.80 (0.76,0.85) and 0.80 (0.64,0.99),respectively).No statistical heterogeneity was observed for any evaluation.However,ARBs did not significantly reduce the odds of all-cause mortality,myocardial infarction and heart failure versus control therapy among all of these studies.But ARBs did reduce the odds of cardiac death and heart failure among the heart failure study versus control therapy.Conclusion ARBs have significant ability to reduce risk of developing new-onset type 2 diabetes but does not improve cardiovascular outcomes over the study follow-up periods among all of included studies.

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

    Directory of Open Access Journals (Sweden)

    Matthias Huber

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

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Safety and Tolerability of the Direct Renin Inhibitor Aliskiren in Combination with Angiotensin Receptor Blockers and Thiazide Diuretics: A Pooled Analysis of Clinical Experience of 12,942 Patients

    Science.gov (United States)

    White, William B.; Bresalier, Robert; Kaplan, Allen P.; Palmer, Biff F.; Riddell, Robert H.; Lesogor, Anastasia; Chang, William; Keefe, Deborah L.

    2011-01-01

    Combinations of the direct renin inhibitor aliskiren with angiotensin receptor blockers (ARBs) or diuretics are effective therapeutic regimens for the treatment of hypertension. A large database of safety information has become available during the past several years with aliskiren in combination trials. Data were pooled from nine short-term (8-week) and four longer-term (26–52-week) randomized, controlled trials of aliskiren in patients with hypertension. Adverse event (AE) rates were assessed for aliskiren combination therapy compared to component monotherapies. In short-term studies, overall AE rates were similar for those receiving aliskiren/valsartan or aliskiren/diuretic combinations (32.2–39.8%) and those receiving the component monotherapies (30.0–39.6%). In longer-term studies, AE rates with aliskiren/losartan (55.5%) and aliskiren/diuretic (45.0%) combination therapy were similar to those with losartan (53.9%) and diuretic (48.9%) alone. Angioedema and hyperkalemia occurred in similar proportions of patients on combination therapies versus monotherapy. In conclusion, the safety and tolerability profile of aliskiren in combination with the ARBs valsartan or losartan, or diuretic is similar to aliskiren, ARBs or diuretic alone. PMID:21029339

  1. Safety and tolerability of the direct renin inhibitor aliskiren in combination with angiotensin receptor blockers and thiazide diuretics: a pooled analysis of clinical experience of 12,942 patients.

    Science.gov (United States)

    White, William B; Bresalier, Robert; Kaplan, Allen P; Palmer, Biff F; Riddell, Robert H; Lesogor, Anastasia; Chang, William; Keefe, Deborah L

    2011-07-01

    Combinations of the direct renin inhibitor aliskiren with angiotensin receptor blockers (ARBs) or diuretics are effective therapeutic regimens for the treatment of hypertension. A large database of safety information has become available during the past several years with aliskiren in combination trials. Data were pooled from 9 short-term (8-week) and 4 longer-term (26- to 52-week) randomized controlled trials of aliskiren in patients with hypertension. Adverse event (AE) rates were assessed for aliskiren combination therapy compared with component monotherapies. In short-term studies, overall AE rates were similar for patients receiving aliskiren/valsartan or aliskiren/diuretic combinations (32.2%-39.8%) and those receiving the component monotherapies (30.0%-39.6%). In longer-term studies, AE rates with aliskiren/losartan (55.5%) and aliskiren/diuretic (45.0%) combination therapy were similar to those with losartan (53.9%) and diuretic (48.9%) alone. Angioedema and hyperkalemia occurred in similar proportions of patients taking combination therapies vs monotherapy. The safety and tolerability profile of aliskiren in combination with the ARBs valsartan or losartan, or diuretic, is similar to aliskiren, ARBs, or diuretics alone.

  2. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition.

    Science.gov (United States)

    Hubers, Scott A; Brown, Nancy J

    2016-03-15

    Heart failure affects ≈5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the US Food and Drug Administration approved the first of a new class of drugs for the treatment of heart failure: Valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses 2 of the pathophysiological mechanisms of heart failure: activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared with enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacological properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension.

  3. Cost effectiveness of angiotensin receptor blocker monotherapy in patients with hypertension in the Netherlands : a comparative analysis using clinical trial and drug utilization data

    NARCIS (Netherlands)

    Boersma, C.; Voors, A.A.; Visser, Sipke; de Jong-van den Berg, L.T.W.; Postma, M.J.

    2010-01-01

    Background and Objective: Health gains and related cost savings achieved by optimizing treatment in hypertensive patients is highly important. The aim of this study was to evaluate the costs and cost effectiveness of treatment with angiotensin II receptor antagonists (angiotensin II receptor blocker

  4. Telmisartan induced urticarial vasculitis.

    Science.gov (United States)

    Mahajan, Vikram K; Singh, Ravinder; Gupta, Mrinal; Raina, Rashmi

    2015-01-01

    A 53-year-old man developed urticarial vasculitis following ingestion of telmisartan and hydrochlorothiazide combination for hypertension. Treatment with prednisolone and cetirizine was curative, but his lesions recurred when he continued telmisartan and hydrochlorothiazide against medical advice. Re-challenge with the same doses of telmisartan precipitated similar lesions with telmisartan and not with hydrochlorothiazide. This uncommon cutaneous adverse reaction of angiotensin II receptor blockers has implication for the clinicians as more such cases may become apparent with their wider use than in premarketing studies.

  5. Telmisartan induced urticarial vasculitis

    Directory of Open Access Journals (Sweden)

    Vikram K Mahajan

    2015-01-01

    Full Text Available A 53-year-old man developed urticarial vasculitis following ingestion of telmisartan and hydrochlorothiazide combination for hypertension. Treatment with prednisolone and cetirizine was curative, but his lesions recurred when he continued telmisartan and hydrochlorothiazide against medical advice. Re-challenge with the same doses of telmisartan precipitated similar lesions with telmisartan and not with hydrochlorothiazide. This uncommon cutaneous adverse reaction of angiotensin II receptor blockers has implication for the clinicians as more such cases may become apparent with their wider use than in premarketing studies.

  6. 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

    Science.gov (United States)

    2011-01-01

    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 registration number Clinical

  7. 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

  8. The combination of amlodipine and angiotensin receptor blocker or diuretics in high-risk hypertensive patients: rationale, design and baseline characteristics

    Science.gov (United States)

    Wang, W; Ma, L; Zhang, Y; Deng, Q; Liu, M; Liu, L

    2011-01-01

    The Chinese Hypertension Intervention Efficacy Study (CHIEF) is a multi-centre randomized controlled clinical trial comparing the effects of amlodipine+angiotensin II receptor blocker and amlodipine+diuretics on the incidence of cardiovascular events, represented as a composite of non-fatal stroke, non-fatal myocardial infarction and cardiovascular death events in high-risk Chinese hypertensive patients. The study also evaluates the long-term effects of lipid-lowering treatment and lifestyle modification. From October 2007 to October 2008, 13 542 patients were enrolled into the study in 180 centres in China. Patients will be followed up for 4 years. There was no difference in baseline characteristics between the two blood pressure arms. PMID:20445570

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

    Directory of Open Access Journals (Sweden)

    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.

  10. The telmisartan renoprotective study from incipient nephropathy to overt nephropathy--rationale, study design, treatment plan and baseline characteristics of the incipient to overt: angiotensin II receptor blocker, telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study.

    Science.gov (United States)

    Makino, H; Haneda, M; Babazono, T; Moriya, T; Ito, S; Iwamoto, Y; Kawamori, R; Takeuchi, M; Katayama, S

    2005-01-01

    We planned the INNOVATION study to determine whether telmisartan, an angiotensin-2-receptor blocker, delays the progression of renal disease from incipient nephropathy to overt nephropathy in hypertensive or normotensive Japanese patients with type 2 diabetes mellitus. The INNOVATION study is a randomized, double-blind, placebo-controlled trial. Eligible patients must have incipient nephropathy (defined as a urinary albumin to creatinine ratio of 100-300 mg/g creatinine) and a serum creatinine concentration of 300 mg/g creatinine and 30% higher than the baseline on at least two consecutive visits). A total of 1855 patients have been enrolled from 160 study centres. In 527 randomized patients (28.4% of the enrolled patients), mean (SD) urinary albumin to creatinine ratio and serum creatinine concentration at baseline were 173.3 (47.2) mg/g creatinine and 0.78 (0.19) mg/dl. Sixty-eight per cent of the patients had hypertension at baseline. Mean (SD) systolic and diastolic blood pressures at baseline were 137.1 (14.6) and 77.5 (10.3) mmHg. The INNOVATION study will determine whether telmisartan, an angiotensin II receptor blocker, provides clinical benefits in hypertensive or normotensive patients with diabetes mellitus and diabetic nephropathy.

  11. Applications of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the treatment of chronic heart failure%血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂在慢性心力衰竭治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    居海宁; 卞金陵

    2011-01-01

    Heart failure is the ultimate cause of death in a variety of heart diseases. It has been discovered that the main strategy of slowing the progress of heart failure diseases is blocking the renin angiotensin aldosterone system (RAAS). Angiotensin converting enzyme inhibitors(ACEI) and angiotensin receptor blockers( ARB) are the most commonly used RAAS-blocking drugs. In this paper,the assessment of chronic heart failure and the applications of ACEI and ARB in the treatment of chronic heart failure are reviewed.%心力衰竭是多种心脏病的最终死亡原因,阻断肾素-血管紧张素-醛固酮系统(renin angiotensin aldosterone system,RAAS)是减慢心力衰竭病变进展的主要策略.血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitors,ACEI)和血管紧张素受体拮抗剂(angiotensin receptor blockers,ARB)是目前最常用的阻断RAAS的药物.本文对慢性心力衰竭评估,以及ACEI和ARB在慢性心力衰竭治疗中的应用进行综述.

  12. Long-term safety and efficacy of telmisartan/amlodipine single pill combination in the treatment of hypertension

    Directory of Open Access Journals (Sweden)

    Billecke SS

    2013-03-01

    Full Text Available Scott S Billecke, Pamela A Marcovitz Beaumont Health System, Ministrelli Women’s Heart Center, Royal Oak, MI, USA Abstract: The use of multiple drug regimens is increasingly recognized as a tacit requirement for the management of hypertension, a necessity fueled in part by rising rates of metabolic syndrome and diabetes. By targeting complementary pathways, combinations of antihypertensive drugs can be applied to provide effective blood pressure control while minimizing side effects and reducing exposure to high doses of individual medications. In addition, combination therapies, including angiotensin converting enzyme (ACE inhibitors and calcium channel blockers (CCBs, have the added benefit of reducing cardiovascular mortality and morbidity over other dual therapies while providing equivalent blood pressure control. It is possible that angiotensin receptor blockers (ARBs, which unlike ACE inhibitors are minimally affected by upregulation of alternative pathways for angiotensin II accumulation following long-term treatment, would also provide such outcome benefits. At issue, however, is maintaining patient compliance, as adding medications is known to reduce adherence to treatment regimens. The purpose of this review is to summarize existing trial data for the long-term safety and efficacy of a recent addition to the armamentarium of dual-antihypertensive therapeutic options, the telmisartan/amlodipine single pill combination. The areas where long-term data are lacking, notably clinical information regarding minorities and women, will also be discussed. Keywords: Angiotensin receptor blocker, antihypertensive, calcium channel blocker, clinical trial, combination pill

  13. Renovascular and renoprotective properties of telmisartan: clinical utility

    Directory of Open Access Journals (Sweden)

    Marco Ladino

    2010-03-01

    Full Text Available Marco Ladino, Ivonne Hernandez SchulmanNephrology-Hypertension Section, Veterans Affairs Medical Center and Division of Nephrology and Hypertension and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Chronic kidney disease (CKD affects approximately 26 million adults in the United States and millions of others are at increased risk. Type 2 diabetes and hypertension are the two main causes of CKD. Blood pressure control is critical to slow the progression of CKD. Despite adequate control, however, patients continue to progress to end-stage renal disease. Angiotensin receptor blockers (ARBs are commonly used in the management of hypertension and CKD and have been shown to exert renoprotective effects that are in addition to, but independent of, blood pressure lowering. Telmisartan is a long-acting ARB with pharmacological properties beyond blockade of the angiotensin II type 1 receptor, including activation of the peroxisome proliferator activated receptor-γ (PPAR-γ. This article reviews the beneficial renal and vascular protective effects of telmisartan.Keywords: kidney diseases, hypertension, vascular diseases, angiotensin II receptor, PPAR-γ

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

    Science.gov (United States)

    Tseng, Chi-Hong; Milne, Ginger L.

    2017-01-01

    Objectives Arachidonic acid metabolites (eicosanoids) reflect oxidative stress and vascular health and have been associated with anthropometric measures and sex differences in cross-sectional analyses of HIV-infected (HIV+) persons. Telmisartan is an angiotensin receptor blocker and PPAR-γ agonist with potential anti-inflammatory and metabolic benefits. We assessed telmisartan’s effects on urine eicosanoids among HIV+ adults with central adiposity on suppressive antiretroviral therapy enrolled in a prospective clinical trial. Methods Thirty-five HIV+ adults (15 women; 20 men) completed 24 weeks of open-label oral telmisartan 40mg daily. Lumbar computed tomography quantified visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue. Urine F2-isoprostane (F2-IsoP), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB-M) were quantified at baseline and 24 weeks using gas/liquid chromatography-mass spectroscopy. Mann-Whitney-U tests compared sub-group differences; Spearman’s rho assessed correlations between clinical factors and eicosanoid levels. Results Median PGE-M increased on telmisartan (p5% VAT (+3.7 ng/mg cr, p5% SAT (+1.7 ng/mg cr, p = 0.04). Median baseline F2-IsoP and TxB-M were slightly higher in women (both between-group p = 0.08) and did not change on telmisartan. Conclusions Urine PGE-M increased with 24 weeks of telmisartan in virally suppressed, HIV+ adults with central adiposity. Associations with favorable fat redistribution suggest increased PGE-M may reflect a beneficial response. PMID:28118376

  15. Antiinflammatory effect of telmisartan on chronic obstructive pulmonary disease: 8-isoprostane concentration in exhaled breath condensate

    Directory of Open Access Journals (Sweden)

    Abdülkadir Geylani Şahan

    2014-06-01

    Full Text Available Aim. Chronic obstructive pulmonary disease (COPD is a chronic, progressive, inflammatory disease. Oxidative stress and airway inflammation are its main pathophysiologic components. In this study, our aim was to investigate the effect of an angiotensin receptor blocker (ARB telmisartan which also exerts antiinflammatory effects on inflammation and oxidative stress in COPD. Method. The study group consisted of 50 stable COPD patients including 25 telmisartan users. Exhaled breath condensate (EBC samples of the cases were collected using an EBC collecting device (Ecoscreen, Jaeger, Germany. EBC samples were analyzed and 8-isoprostane levels were measured using an enzyme immunoassay method (Cayman Chemical Co. Michigan, USA. Results. Any intergroup difference as for mean age, distribution of gender and smoking were not found. In telmisartan users, and nonusers mean 8-isoprostane levels were 33.98 and 35.91 pg/mL, respectively with a statistically significant intergroup difference (p<0.001 Conclusion. We think that ARBs decrease oxidative stress and inflammation, and thus exert favourable effects on the pathophysiology and progression of COPD.

  16. Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium.

    Science.gov (United States)

    Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Karuppagounder, Vengadeshprabhu; Pitchaimani, Vigneshwaran; Afrin, Mst Rejina; Miyashita, Shizuka; Nomoto, Mayumi; Harima, Meilei; Suzuki, Hiroshi; Nakamura, Takashi; Nakamura, Masahiko; Suzuki, Kenji; Watanabe, Kenichi

    2015-08-01

    The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1β, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.

  17. Effect of telmisartan on expression of protein kinase C-α in kidneys of diabetic mice

    Institute of Scientific and Technical Information of China (English)

    Li-jun YAO; Jian-qing WANG; Hong ZHAO; Jian-she LIU; An-guo DENG

    2007-01-01

    Aim: To investigate the effects of angiotensin receptor blocker (ARB) telmisartan on the expression and distribution of protein kinase C (PKC)-α in the kidneys of diabetic mice.Methods: Diabetic mice were induced with streptozotocin and a group of them were randomly selected for treatment with telmisartan. After 6 weeks, the expression and localization of PKC-α in the renal cortex, and the outer and inner medulla were assessed by immunohistochemistry and semiquantitative Western blotting. In addition, expressions of PKC-α, transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF) in glomemli were measured by semiquantitative immunohistochemistry.Results: Diabetic and nor-mal mice showed similar distributions of PKC-α in the kidneys. The expression of PKC-α was found in glomeruli, epithelial cells of proximal tubules, and medullary-collecting duct, while not in the medullary and cortical thick ascending limb, and was different in the epithelial cells of proximal tubules of diabetic nephropathy (DN) mice, PKC-α was mostly translocated from the basement membrane to the apical membrane, whereas it was largely translocated from the apical membrane to the basement membrane in epithelial cells of the inner medullary-collecting duct.Western blotting detected increased expression of PKC-α in the renal cortex and outer medulla, but not in the inner medulla of DN mice. Enhanced expressions of PKC-α TGF-β, and VEGF were shown in the glomeruli of DN mice, where PKC-α exhibited a correlation to VEGF, but no correlation to TGF-β1. ARB telmisartan attenuated alterations of PKC-α as mentioned earlier in the DN mice.Conclusion: Our findings suggest that PKC-α may play a role in the pathogenesis of DN, and that the nephroprotective effects of ARB telmisartan may be partly associated with its influence on PKC-α.

  18. Safety profiling of pioglitazone and telmisartan combination by sub-chronic toxicity study in rat.

    Science.gov (United States)

    Sengupta, Pinaki; Das, Arindam; Ibrahim, Fuzianna; Mandal, Uttam Kumar; Chatterjee, Bappaditya; Mahmood, Syed; Das, Sreemoy Kanti; Kifayatullah, Muhammad

    2016-11-01

    It has been reported that the major cause of mortality in diabetes is cardiovascular diseases and contribution of hypertension is significant in this context. Pioglitazone, a thiazolidinedione class of therapeutic agent is used to treat type 2 diabetes mellitus. Telmisartan, an angiotensin receptor blocker antihypertensive has been reported to have beneficial effect if co-administered with pioglitazone for the management of diabetes complications. The present research work aims to evaluate the safety/toxicity profile of this combination in rat model. The investigation was carried out after co-administering the drugs to the rats for 28 days at three dose levels of 50, 100 and 150 mg/kg covering low to high dose ranges. Various hematological and biochemical parameters were studied in addition to the histopathology of the major organs in order to evaluate the toxicity profile of the combination. Absence of mortality and histopathological changes as well as unaltered hematological and biochemical parameters was observed. This preliminary investigation concludes that the combination of pioglitazone and telmisartan can primarily be stated as safe in animals, even at the dose level which is several folds higher than the intended human dose. Thus, this combination can be explored in future to develop a rational therapy regimen to treat hypertensive diabetic patients.

  19. Telmisartan, ramipril, or both in high-risk Chinese patients: analysis of ONTARGET China data

    Institute of Scientific and Technical Information of China (English)

    YU Li-tian; ZHU Jun; TAN Hui-qiong; WANG Guo-gan; Koon K.Teo; LIU Li-sheng

    2011-01-01

    Background The results from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) indicated that the angiotensin-receptor blocker telmisartan was not inferior to the angiotensin-converting-enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke or hospitalization for congestive heart failure in high-risk patients, and telmisartan was associated with slightly superior tolerability. The combination of the two drugs was associated with more adverse events without an increase in benefit. This study aimed to analyze the data from ONTARGET obtained from a subgroup of patients enrolled in China and to evaluate the demographic and baseline characteristics, the compliance, efficacy, and safety of the different treatment strategies in randomized patients in China.Methods A total of 1159 high-risk patients were randomized into three treatment groups: with 390 assigned to receive 80 mg of telmisartan, 385 assigned to receive 10 mg of ramipril and 384 assigned to receive both study medications. The median follow-up period was 4.3 years.Results The mean age of Chinese patients was 65.6 years, 73.6% of patients were male. The proportion of patients with stroke/transient ischemic attacks at baseline in China was two times more than the entire study population (47.7% vs. 20.9%). In Chinese patients the proportion of permanent discontinuation of study medication due to cough was 0.5% in the telmisartan group, which was much less than that in the combination or the ramipril group. There were no significant differences in the incidence of primary outcome among three treatment groups of Chinese patients. More strokes occurred in Chinese patients than in the entire study population (8.5% vs. 4.5%). Greater systolic blood pressure reduction (-9.8 mmHg), and more renal function failure were noted in the combination treatment group than in the ramipril or telmisartan group (2.6% vs. 1

  20. Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing period, including the critical early morning hours: a pooled analysis of the PRISMA I and II randomized trials.

    Science.gov (United States)

    Williams, B; Lacourcière, Y; Schumacher, H; Gosse, P; Neutel, J M

    2009-09-01

    Cardiovascular risk is subject to circadian variation, with peak morning incidence of myocardial infarction and stroke correlating with the early morning blood pressure (BP) surge (EMBPS). Ideally, antihypertensive therapy should maintain control of BP throughout the 24-h dosing cycle. In two sister studies, Prospective, Randomized Investigation of the Safety and efficacy of Micardis vs Ramipril Using ABPM (ambulatory BP monitoring) (PRISMA) I and II, BP control was compared in patients with essential hypertension (24-h mean baseline ambulatory BP approximately 148/93 mm Hg) randomized to the angiotensin receptor blocker, telmisartan (80 mg; n=802), or the angiotensin-converting enzyme inhibitor, ramipril (5 or 10 mg; n=811), both dosed in the morning. The primary end point was the change from baseline in mean ambulatory systolic BP (SBP) and diastolic BP (DBP) during the final 6 h of the 24-h dosing cycle. The adjusted mean treatment differences in the last 6-h mean ambulatory SBP/DBP were -5.8/-4.2 mm Hg after 8 weeks and -4.1/-3.0 mm Hg after 14 weeks, in favour of telmisartan (P<0.0001 for all four comparisons). Secondary end point results, including the mean 24-h ambulatory BP monitoring, day- and night-time BP and 24-h BP load, also significantly favoured telmisartan (P<0.0001). Both treatments were well tolerated; adverse events, including cough, were less common with telmisartan. These findings suggest that telmisartan is more effective than ramipril throughout the 24-h period and during the EMBPS; this may be attributable to telmisartan's long duration of effect, which is sustained throughout the 24-h dosing period.

  1. Association of Renin-angiotensin-aldosterone System Gene Polymorphism with the Effect of Angiotensin Receptor Blockers%肾素-血管紧张素-醛固酮系统基因多态性与血管紧张素受体阻滞剂降压疗效相关性的研究进展

    Institute of Scientific and Technical Information of China (English)

    贾坚; 门琛

    2012-01-01

    People recognize that the difference of genetic polymorphism results in the individual difference of drug effect, as the development of the human genome project and pharmacogenomics. This paper reviews association of renin-angiotensin-aldosterone system gene polymorphism with the effect of angiotensin receptor blockers which are used commonly in clinic. The paper also analyzes the possible causes of the contradiction of the research results in the past.%随着人类基因组计划的实施以及药物基因组学研究的进展,人们认识到基因多态性的不同导致了药物治疗效果的个体差异.现综述肾素-血管紧张素-醛固酮系统基因多态性与临床上常用的血管紧张素受体阻滞剂降压疗效的相关性,并分析以往研究结果矛盾的可能原因.

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

    NARCIS (Netherlands)

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

    2016-01-01

    Aims: To predict individualized treatment effects of angiotensin receptor blockers (ARBs) on cardiovascular and renal complications in order to help clinicians and patients assess the benefit of treatment (or adherence) and estimate remaining disease risk. Materials and methods: In patients with dia

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

    NARCIS (Netherlands)

    van der Sande, Nicolette G C; Dorresteijn, Jannick A N; Visseren, Frank L J; Dwyer, Jamie P; Blankestijn, Peter J; van der Graaf, Yolanda; Heerspink, Hiddo L

    2016-01-01

    Aims Angiotensin receptor blockers (ARBs) reduce cardiovascular and renal complications in patients with diabetic nephropathy but treatment effects may vary across patients. Predicting individualized treatment effect of ARBs on both outcomes may help clinicians and patients to assess the benefit of

  4. To compare the effect of Telmisartan with Metoprolol on arterial stiffness in hypertension: Prospective randomized parallel group trial

    Science.gov (United States)

    Sumbria, Minakshi; Negi, Prakash C.; Sahai, Ashok K.; Kaundal, Purshotam K.

    2014-01-01

    Background Hypertension is often complicated by increased arterial stiffness and is an independent predictor of adverse cardiovascular (CV) outcome. Beta blockers and angiotensin receptor blockers (ARBs) are commonly used antihypertensive agents. The effect of beta blockers and ARBs on arterial stiffness has not been compared adequately. The aim of the present study is to compare the effect of telmisartan with metoprolol on arterial stiffness in hypertensive patients in prospective open label randomized parallel group intervention study. Methods 100 patients of hypertension, not on any antihypertensive agents, were enrolled after obtaining informed consent. Baseline recording of data related to demographics, CV risk factors, anthropometry and BP were made. Arterial stiffness was measured noninvasively by recording pulse wave velocity (PWV) using periscope (Genesis medical system). Left ventricular (LV) mass was measured using 2D guided M-mode echocardiography. Blood sugar, renal function, lipids and uric acid estimations were done in fasting state. Patients were randomized to receive metoprolol and telmisartan using stratified randomization technique. Dose of the study drugs were titrated to achieve target BP of <140/90 mmHg. Data related to PWV, BP, anthropometry and blood biochemistry was repeated after 6 months of treatment with study drugs. Results Telmisartan resulted in significantly greater reduction in arterial stiffness index (ASI) in left and right lower limb arterial bed (39.9 ± 11.7 vs. 46.8 ± 17.0 m/s, p < 0.02) and (36.4 ± 9.6 vs. 44.86 ± 15.1 m/s, p < 0.002) respectively and systolic blood pressure (SBP) (−4.9 mmHg with 95% C.I. of −8.0–1.7 mmHg, p < 0.003) compared to metoprolol. Reduction in diastolic blood pressure (DBP) in telmisartan and metoprolol groups was not different statistically (−1.0 mmHg with 95% C.I. of −3.3–1.2 mmHg, p < 0.3). The change in LV mass was not significantly different between the

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

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2012-01-01

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

  6. [Assessment of the utilization of angiotensin receptor blockers in hypertension].

    Science.gov (United States)

    Peña Cabia, S; Ricote Lobera, I; Santos Mena, B; Hidalgo Correas, F J; Climent Florez, B; García Díaz, B

    2013-01-01

    Objetivo: Evaluar en nuestra área de Salud el grado en que la utilización de antagonistas de los receptores de la angiotensina II (ARA-II) se ajusta a los criterios propuestos por la Comunidad Autónoma de Madrid (CAM) antes de la instauración del «Plan de Actuación de ARA-II». Estudiar las indicaciones para las que se prescriben e identificar aquellos factores que han podido influir en su prescripción. Métodos: Estudio de utilización de medicamentos del tipo indicación- prescripción, descriptivo y transversal, en el que se seleccionaron pacientes con hipertensión arterial y en tratamiento con ARA-II ingresados en un Hospital General Universitario durante un periodo de estudio de 3 meses. De acuerdo con las situaciones clínicas recogidas en el Documento de la CAM «Criterios para establecer el lugar en la terapéutica de los antagonistas de los receptores de la angiotensina II», se calculó el porcentaje de pacientes con «prescripción adecuada» y «prescripción no adecuada» de ARA-II y se analizó si la edad y el sexo tenían influencia en el tipo de prescripción o en las principales indicaciones para las que se prescribieron. Resultados: De los 153 pacientes que se incluyeron en el estudio, el 67,3% tuvieron una «prescripción no adecuada», el 47,6% de ellos por prescripción de ARA-II como primer fármaco antagonista del sistema renina angiotensina aldosterona y el 34,0% por mal control de la tensión arterial con inhibidores de la enzima convertidora de angiotensina (IECA). No se encontraron diferencias estadísticamente significativas por edad o sexo en cuanto al tipo de prescripción o en las principales indicaciones para las que se prescribieron. Conclusiones: La adecuación a los criterios de uso del Documento de ARA-II se produjo en el 32,7% de los casos. Además, no se observó que factores como la edad y el sexo influyeran en el tipo de prescripción. Asimismo, se evidenciaron percep-

  7. 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...

  8. Telmisartan and Hydrochlorothiazide

    Science.gov (United States)

    Micardis® HCT (as a combination product containing Telmisartan, Hydrochlorothiazide) ... Combination productThis product contains two medications, telmisartan and hydrochlorothiazide. Please see the individual monographs for information about each of the medications contained in this product.

  9. Telmisartan induced urticarial vasculitis

    OpenAIRE

    Vikram K Mahajan; Ravinder Singh; Mrinal Gupta; Rashmi Raina

    2015-01-01

    A 53-year-old man developed urticarial vasculitis following ingestion of telmisartan and hydrochlorothiazide combination for hypertension. Treatment with prednisolone and cetirizine was curative, but his lesions recurred when he continued telmisartan and hydrochlorothiazide against medical advice. Re-challenge with the same doses of telmisartan precipitated similar lesions with telmisartan and not with hydrochlorothiazide. This uncommon cutaneous adverse reaction of angiotensin II receptor bl...

  10. Telmisartan/Hydrochlorothiazide: a review of its use as fixed-dose combinations in essential hypertension.

    Science.gov (United States)

    Plosker, Greg L; White, William B

    2008-01-01

    Fixed-dose combinations of telmisartan and hydrochlorothiazide (HCTZ) [Micardis Plus, Micardis HCT, PritorPlus] are available in many countries for the treatment of patients with essential hypertension. Combining the angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) telmisartan with the thiazide diuretic HCTZ provides antihypertensive therapy with complementary mechanisms of action. In the US and EU, telmisartan/HCTZ is approved for patients whose hypertension is not adequately controlled with telmisartan monotherapy; US labelling for the fixed-dose combination also includes inadequate control of blood pressure (BP) with HCTZ monotherapy.The antihypertensive efficacy of once-daily telmisartan/HCTZ has been demonstrated in several large, randomized trials in patients with stages 1 and 2 hypertension. The addition of HCTZ to telmisartan achieved significant reductions in BP in nonresponders to telmisartan monotherapy, and the antihypertensive efficacy of telmisartan/HCTZ was similar to or significantly greater than that of various comparator agents. Moreover, in studies that used ambulatory BP monitoring, telmisartan/HCTZ provided consistent 24-hour BP reductions throughout morning, daytime and night-time periods. The BP-lowering efficacy over the entire 24-hour dose administration interval is consistent with the pharmacokinetic profile of telmisartan, which has the longest elimination half-life among currently available ARBs and a unique chemical structure. Adverse events with telmisartan/HCTZ in clinical trials were typically mild and transient, and no unexpected events occurred that had not been previously reported with either telmisartan or HCTZ. Extensive tolerability data are available for telmisartan, in particular from the ONTARGET study, the largest clinical outcomes trial with an ARB. As such, fixed-dose combinations of telmisartan/HCTZ provide an effective, rational and generally well tolerated treatment option for the management

  11. [Angiotensin-receptor- and neprilysin-inhibition: a new option against heart failure].

    Science.gov (United States)

    Bruhn, Claudia

    2016-01-01

    The molecular combination of sacubitril and valsartan (Entresto) is a new drug for reducing the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. It is usually administered in conjunction with other heart failure therapies, instead of an ACE inhibitor or an angiotensin-receptor blocker (ARB). In studies, sacubitril/ valsartan was superior to enalapril in reducing the risks of death and hospitalization for heart failure. Possible side effects of sacubitril/valsartan are hypotension, angioedema, impaired renal function and elevation in serum potassium levels. The drug should not be used in times of pregnancy and breast feeding, in patients with servere hepatic impairment (Child-Pugh C) and in combination with aliskiren in patients with diabetes.

  12. Angiotensin receptor antagonists to prevent sudden death in heart failure: does the dose matter?

    Science.gov (United States)

    Francia, Pietro; Palano, Francesca; Tocci, Giuliano; Adduci, Carmen; Ricotta, Agnese; Semprini, Lorenzo; Caprinozzi, Massimo; Balla, Cristina; Volpe, Massimo

    2014-01-01

    International guidelines recommend ICD implantation in patients with severe left ventricular dysfunction of any origin only after careful optimization of medical therapy. Indeed, major randomized clinical trials suggest that suboptimal use of fundamental drugs, such as ACE inhibitors (ACE-i) and beta-blockers, may affect ICD shock-free survival, sudden cardiac death (SCD), and overall mortality. While solid evidence in favour of pharmacological therapy based on ACE-i with or without beta-blockers is available, data on SCD in HF patients treated with angiotensin receptor blockers (ARBs) are limited. The present paper systematically analyses the impact of ARBs on SCD in HF and reviews the contributory role of the renin-angiotensin system (RAS) to the establishment of arrhythmic substrates. The following hypothesis is supported: (1) the RAS is a critical component of the electrical remodelling of the failing myocardium, (2) RAS blockade reduces the risk of SCD, and (3) ARBs represent a powerful tool to improve overall survival and possibly reduce the risk of SCD provided that high doses are employed to achieve optimal AT1-receptor blockade.

  13. Telmisartan attenuates hepatic fibrosis in bile duct-ligated rats

    Institute of Scientific and Technical Information of China (English)

    En-tong YI; Rui-xia LIU; Yan WEN; Cheng-hong YIN

    2012-01-01

    Aim: To evaluate the antifibrotic effect of telmisartan,an angiotensin Ⅱ receptor blocker,in bile duct-ligated rats.Methods: Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats,model rats underwent common bile duct ligation (BDL),and BDL rats treated with telmisartan (8 mg/kg,po,for 4 weeks).The animals were sacrificed on d 29,and liver histology was examined,the Knodell and Ishak scores were assigned,and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining.The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot,respectively.Results: The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35,P=0.015).However,there was no significant difference in inflammation between the two groups,both of which showed moderate inflammation.Histologically,treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis.Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS,and decreased the mRNA levels of ACE,angiotensin Ⅱ type 1 receptor (AT1-R),collagen type Ⅲ,and transforming growth factor β1 (TGF-β1).Moreover,treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins,and inhibited the expression levels of ACE and AT1-R protein.Conclusion: Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.

  14. Angiotensin receptor neprilysin inhibition in heart failure: mechanistic action and clinical impact.

    Science.gov (United States)

    Buggey, Jonathan; Mentz, Robert J; DeVore, Adam D; Velazquez, Eric J

    2015-09-01

    Heart failure (HF) is an increasingly common syndrome associated with high mortality and economic burden, and there has been a paucity over the past decade of new pharmacotherapies that improve outcomes. However, recent data from a large randomized controlled trial compared the novel agent LCZ696, a dual-acting angiotensin receptor blocker and neprilysin inhibitor (ARNi), with the well established angiotensin-converting enzyme (ACE) inhibitor enalapril and found significant reduction in mortality among the chronic reduced ejection fraction HF population. Preclinical and clinical data suggest that neprilysin inhibition provides beneficial outcomes in HF patients by preventing the degradation of natriuretic peptides and thereby promoting natriuresis and vasodilatation and counteracting the negative cardiorenal effects of the up-regulated renin-angiotensin-aldosterone system. Agents such as omapatrilat combined neprilysin and ACE inhibition but had increased rates of angioedema. Goals of an improved safety profile provided the rationale for the development of the ARNi LCZ696. Along with significant reductions in mortality and hospitalizations, clinical trials suggest that LCZ696 may improve surrogate markers of HF severity. In this paper, we review the preclinical and clinical data that led to the development of LCZ696, the understanding of the underlying mechanistic action, and the robust clinical impact that LCZ696 may have in the near future.

  15. β受体阻滞剂分别联合血管紧张素受体拮抗剂和钙离子拮抗剂治疗江门地区中青年高血压的临床效果观察%Curative Effect of Beta-blockers Respectively Combination of Angiotensin Receptor Blockers and Calcium Antagonists in the Treatment of Young and Middle-Aged High Blood Pressure in Jiangmen

    Institute of Scientific and Technical Information of China (English)

    黄享贞; 钟洁霞

    2015-01-01

    目的:比较β受体阻滞剂分别联合血管紧张素受体拮抗剂(ARB)和钙离子拮抗剂(CCB)治疗江门地区中青年高血压的治疗效果。方法:选取2012年12月-2014年12月收治的江门地区中青年高血压患者300例,随机数字表法分为观察组和对照组各150例。观察组患者给予ARB联合β受体阻滞剂治疗,对照组给予CCB联合β受体阻滞剂治疗,观察两组治疗前后的血压、心率变化情况以及降压疗效和症状改变情况。结果:治疗8周后两组患者的血压、心率均较治疗前下降(P0.05),观察组心率下降较对照组明显,差异有统计学意义(P0.05),heart rate decline in treatment group and control group,the difference was statistically significant(P<0.05).In terms of hypertension treatment,observation group total effective rate was 94.67%,control group total effective rate was 82.00%, total effective rate of observation group was obviously higher than that of control group,the difference was statistically significant (P<0.05).In terms of symptom improvement,observation group total effective rate was 96.67%,control group total effective rate was 84.67%,total effective observation group was obviously higher than that of control group,the difference was statistically significant(P<0.05).Conclusion:The application of combined beta-blockers ARB can significantly reduce the diastolic and systolic blood pressure of patients,slow heart rate,and in terms of antihypertensive effects and symptoms improve curative effect is good,worthy of clinical promotion.

  16. Angiotensin receptor blockade recovers hepatic UCP2 expression and aconitase and SDH activities and ameliorates hepatic oxidative damage in insulin resistant rats.

    Science.gov (United States)

    Montez, Priscilla; Vázquez-Medina, José Pablo; Rodríguez, Rubén; Thorwald, Max A; Viscarra, José A; Lam, Lisa; Peti-Peterdi, Janos; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M

    2012-12-01

    Metabolic syndrome (MetS) is commonly associated with elevated renin-angiotensin system, oxidative stress, and steatohepatitis with down-regulation of uncoupling proteins (UCPs). However, the mechanisms linking renin-angiotensin system, steatosis, and UCP2 to hepatic oxidative damage during insulin resistance are not described. To test the hypothesis that angiotensin receptor activation contributes to decreased hepatic UCP2 expression and aconitase activity and to increased oxidative damage after increased glucose intake in a model of MetS, lean and obese Long Evans rats (n = 10/group) were randomly assigned to the following groups: 1) untreated Long Evans Tokushima Otsuka (lean, strain control), 2) untreated Otsuka Long Evans Tokushima Fatty (OLETF) (MetS model), 3) OLETF + angiotensin receptor blocker (ARB) (10 mg olmesartan/kg·d × 6 wk), 4) OLETF + high glucose (HG) (5% in drinking water × 6 wk), and 5) OLETF + ARB + HG (ARB/HG × 6 wk). HG increased body mass (37%), plasma triglycerides (TGs) (35%), plasma glycerol (87%), plasma free fatty acids (28%), and hepatic nitrotyrosine (74%). ARB treatment in HG decreased body mass (12%), plasma TG (15%), plasma glycerol (23%), plasma free fatty acids (14%), and hepatic TG content (42%), suggesting that angiotensin receptor type 1 (AT1) activation and increased adiposity contribute to the development of obesity-related dyslipidemia. ARB in HG also decreased hepatic nitrotyrosine and increased hepatic UCP2 expression (59%) and aconitase activity (40%), as well as antioxidant enzyme activities (50-120%), suggesting that AT1 activation also contributes to protein oxidation, impaired lipid metabolism, and antioxidant metabolism in the liver. Thus, in addition to promoting obesity-related hypertension, AT1 activation may also impair lipid metabolism and antioxidant capacity, resulting in steatosis via decreased UCP2 and tricarboxylic acid cycle activity.

  17. Angiotensin receptor blockers: a panacea for Marfan syndrome and related disorders?

    NARCIS (Netherlands)

    Loeys, B.L.

    2015-01-01

    The study of mouse models for Marfan syndrome, an autosomal dominant connective tissue disorder caused by mutations in fibrillin-1 (FBN1), has shifted our understanding of the pathogenesis of thoracic aortic aneurysm significantly. Multiple lines of evidence support the notion that dysregulation of

  18. Is there any difference between angiotensin converting enzyme inhibitors and angiotensin receptor blockers for heart failure?

    Directory of Open Access Journals (Sweden)

    Carmen Rain

    2015-07-01

    Full Text Available Los antagonistas del receptor de angiotensina son habitualmente considerados equivalentes a los inhibidores de la enzima convertidora de angiotensina en pacientes con insuficiencia cardiaca crónica y fracción de eyección disminuida. Incluso algunas de las principales guías clínicas lo recomiendan como primera alternativa debido a un perfil de efectos adversos más favorable. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos cuatro revisiones sistemáticas que en conjunto incluyen ocho estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que los antagonistas del receptor de angiotensina probablemente tienen el mismo efecto sobre la mortalidad que los inhibidores de la enzima convertidora, y podrían ser equivalentes también en su efecto sobre el riesgo de hospitalizaciones. El abandono de tratamiento por efectos adversos es probablemente menor con antagonistas del receptor de angiotensina que con inhibidores de la enzima convertidora.

  19. Preadmission use of renin-angiotensin blockers and rupture of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Wemmelund, Holger; Høgh, Annette; Hundborg, Heidi H.

    2016-01-01

    PURPOSE: Rupture of abdominal aortic aneurysms (rAAA) is associated with high mortality. Use of angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs) has been suggested to reduce the risk of rAAA. This nationwide, combined case-control and follow...

  20. Telmisartan prevention of LPS-induced microglia activation involves M2 microglia polarization via CaMKKβ-dependent AMPK activation.

    Science.gov (United States)

    Xu, Yuan; Xu, Yazhou; Wang, Yurong; Wang, Yunjie; He, Ling; Jiang, Zhenzhou; Huang, Zhangjian; Liao, Hong; Li, Jia; Saavedra, Juan M; Zhang, Luyong; Pang, Tao

    2015-11-01

    Brain inflammation plays an important role in the pathophysiology of many psychiatric and neurological diseases. During brain inflammation, microglia cells are activated, producing neurotoxic molecules and neurotrophic factors depending on their pro-inflammatory M1 and anti-inflammatory M2 phenotypes. It has been demonstrated that Angiotensin II type 1 receptor blockers (ARBs) ameliorate brain inflammation and reduce M1 microglia activation. The ARB telmisartan suppresses glutamate-induced upregulation of inflammatory genes in cultured primary neurons. We wished to clarify whether telmisartan, in addition, prevents microglia activation through polarization to an anti-inflammatory M2 phenotype. We found that telmisartan promoted M2 polarization and reduced M1 polarization in LPS-stimulated BV2 and primary microglia cells, effects partially dependent on PPARγ activation. The promoting effects of telmisartan on M2 polarization, were attenuated by an AMP-activated protein kinase (AMPK) inhibitor or AMPK knockdown, indicating that AMPK activation participates on telmisartan effects. Moreover, in LPS-stimulated BV2 cells, telmisartan enhancement of M2 gene expression was prevented by the inhibitor STO-609 and siRNA of calmodulin-dependent protein kinase kinase β (CaMKKβ), an upstream kinase of AMPK. Furthermore, telmisartan enhanced brain AMPK activation and M2 gene expression in a mouse model of LPS-induced neuroinflammation. In addition, telmisartan reduced the LPS-induced sickness behavior in this in vivo model, and this effect was prevented by prior administration of an AMPK inhibitor. Our results indicate that telmisartan can be considered as a novel AMPK activator, suppressing microglia activation by promoting M2 polarization. Telmisartan may provide a novel, safe therapeutic approach to treat brain disorders associated with enhanced inflammation.

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

    Science.gov (United States)

    Xia, Yang; Kellems, Rodney E

    2013-06-21

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

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

    Directory of Open Access Journals (Sweden)

    Domenico Galzerano

    2010-03-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  4. Telmisartan in the management of diabetic nephropathy: a contemporary view.

    Science.gov (United States)

    Balakumar, Pitchai; Bishnoi, Harish K; Mahadevan, Nanjaian

    2012-05-01

    Diabetic nephropathy, a complex disorder with heterogeneous etiologies, remains one of the most threatening diseases worldwide. There were around 177 million people with diabetes mellitus worldwide, and it has been estimated to be increased to 360 million by 2030. Given that about 20-30% of these people develop diabetic nephropathy, the present treatment protocols primarily aim for an efficient glucose and blood pressure control to arrest the initiation and progression of diabetic nephropathy. The treatment of diabetic nephropathy near the beginning at microalbuminuria stage with angiotensin-II-AT1 receptor blockers (ARBs) improves blood pressure control and halts disease progression of diabetic nephropathy. In fact, ARBs exert renoprotective effects independently of their blood pressure lowering effect, as they have direct defensive action on the diabetic kidney. Indubitably, it would be better if an ARB has both glucose-lowering and blood pressure controlling potentials efficiently. Intriguingly, telmisartan has such possessions considering its dual role of AT1 receptor blocking action and peroxisome proliferator-activated receptor gamma (PPARγ) partial agonistic property. The additional PPARγ agonistic potential of telmisartan could make it a distinctive intervention in the ARB class to prevent the progression of diabetic nephropathy through activation of PPARγ-mediated insulin sensitization, and renal anti-inflammatory and anti-oxidant actions. Indeed, telmisartan reduced insulin resistance and glucose intolerance, and halted the progressive renal dysfunction associated with diabetic nephropathy by inhibiting the incidence of albuminuria, and preventing the progression of glomerulosclerosis, renal interstitial inflammation and fibrosis. This review will discuss the current status of therapeutic potentials of telmisartan in treating diabetic nephropathy.

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

    Directory of Open Access Journals (Sweden)

    Shimizu Y

    2012-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Singh JSS

    2015-06-01

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

  7. Anti-remodeling effects of rapamycin in experimental heart failure: dose response and interaction with angiotensin receptor blockade.

    Science.gov (United States)

    Bishu, Kalkidan; Ogut, Ozgur; Kushwaha, Sudhir; Mohammed, Selma F; Ohtani, Tomohito; Xu, Xiaolei; Brozovich, Frank V; Redfield, Margaret M

    2013-01-01

    While neurohumoral antagonists improve outcomes in heart failure (HF), cardiac remodeling and dysfunction progress and outcomes remain poor. Therapies superior or additive to standard HF therapy are needed. Pharmacologic mTOR inhibition by rapamycin attenuated adverse cardiac remodeling and dysfunction in experimental heart failure (HF). However, these studies used rapamycin doses that produced blood drug levels targeted for primary immunosuppression in human transplantation and therefore the immunosuppressive effects may limit clinical translation. Further, the relative or incremental effect of rapamycin combined with standard HF therapies targeting upstream regulators of cardiac remodeling (neurohumoral antagonists) has not been defined. Our objectives were to determine if anti-remodeling effects of rapamycin were preserved at lower doses and whether rapamycin effects were similar or additive to a standard HF therapy (angiotensin receptor blocker (losartan)). Experimental murine HF was produced by transverse aortic constriction (TAC). At three weeks post-TAC, male mice with established HF were treated with placebo, rapamycin at a dose producing immunosuppressive drug levels (target dose), low dose (50% target dose) rapamycin, losartan or rapamycin + losartan for six weeks. Cardiac structure and function (echocardiography, catheterization, pathology, hypertrophic and fibrotic gene expression profiles) were assessed. Downstream mTOR signaling pathways regulating protein synthesis (S6K1 and S6) and autophagy (LC3B-II) were characterized. TAC-HF mice displayed eccentric hypertrophy, systolic dysfunction and pulmonary congestion. These perturbations were attenuated to a similar degree by oral rapamycin doses achieving target (13.3±2.1 ng/dL) or low (6.7±2.5 ng/dL) blood levels. Rapamycin treatment decreased mTOR mediated regulators of protein synthesis and increased mTOR mediated regulators of autophagy. Losartan monotherapy did not attenuate remodeling, whereas

  8. Effects of Antihypertensive Agents on Intestinal Contractility in the Spontaneously Hypertensive Rat: Angiotensin Receptor System Downregulation by Losartan

    Science.gov (United States)

    Abeywardena, Mahinda Yapa

    2017-01-01

    Hypertension is an inflammatory condition controlled by the renin angiotensin system and is linked to kidney disease, diabetes mellitus, and recently to dysfunction of the gut. The aim of this study was to determine what effect antihypertensive drug treatments may have on intestinal function of the spontaneously hypertensive rat (SHR). In the first experiment, SHRs were treated with enalapril, hydralazine, or with no treatment as a control. In the second experiment, SHRs were treated with losartan or with no treatment as a control. All drug treatments led to significant lowering of blood pressure after 16 weeks. At termination, intact tissue sections of the ileum and colon were induced to contract ex vivo by KCl; electrical stimulation; and agonists carbachol, angiotensin II, and prostaglandin E2 (PGE2). There were no differences in ileal or colonic contractility due to hydralazine or enalapril compared with no-treatment SHR control. However, for the ileum, the losartan group responded significantly more to KCl and carbachol while responding less to angiotensin II, with no difference for PGE2 compared with the no-treatment SHR control. In contrast, the colon responded similarly to KCl, electrical stimulation, and PGE2 but responded significantly less to angiotensin II. These results demonstrate that the ileum responds differently (with KCl and carbachol as agonists) to the colon after losartan treatment, whereas there is a reduced contractile response in both the ileum and colon following losartan treatment. Although there are few well documented major contraindications for angiotensin receptor blockers, the modulation of gut contractility by losartan may have wider implications for bowel health. PMID:27903643

  9. Importance of a fixed combination of telmisartan and amlodipine for the treatment of hypertension.

    Science.gov (United States)

    Ahrens, K; Bramlage, P

    2010-05-01

    Patients with moderate to severe hypertension frequently require>or=2 antihypertensives to achieve blood pressure (BP) control. The combination telmisartan/amlodipine is especially suitable for the treatment of severely hypertensive, high-risk patients, because it offers a substantial and sustained 24-h BP-lowering effect and is well tolerated in a range of patients with hypertension, who are at risk for cardiovascular events. ACCOMPLISH was the first trial to test two fixed-dose combinations (the angiotensin-converting enzyme inhibitor [ACEi] benazepril in combination with either the diuretic hydrochlorothiazide [HCTZ] or the calcium channel blocker amlodipine). It was shown that a combination including amlodipine was superior to that including HCTZ in reducing the risk of cardiovascular events and death among high-risk patients. Results of the ONTARGET study comparing telmisartan with ramipril showed that telmisartan was an equally effective alternative to ramipril and less likely to cause angioedema. The telmisartan/amlodipine combination is therefore a particularly attractive choice for difficult-to-control hypertensive patients at cardiovascular risk, including those with diabetes, or those who are obese, elderly, not controlled by amlodipine monotherapy, or who are intolerant to ACEi.

  10. Expression of Astrocytic Type 2 Angiotensin Receptor in Central Nervous System Inflammation Correlates With Blood-Brain Barrier Breakdown

    DEFF Research Database (Denmark)

    Füchtbauer, Laila; Toft-Hansen, Henrik; Khorooshi, Reza;

    2010-01-01

    is involved during BBB breakdown. We studied the type 2 angiotensin receptor AT(2) because of its suggested neuroprotective role. Two models of brain inflammation were used to distinguish solute versus cellular barrier functions. Both leukocytes and horseradish peroxidase (HRP) accumulated in the perivascular...

  11. Increasing the doses of both diuretics and angiotensin receptor blockers is beneficial in subjects with uncontrolled systolic hypertension

    Science.gov (United States)

    Lacourcière, Yves; Poirier, Luc; Lefebvre, Jean; Ross, Stuart A; Leenen, Frans H

    2010-01-01

    BACKGROUND: Blood pressure (BP) control is frequently difficult to achieve in patients with predominantly elevated systolic BP. Consequently, these patients frequently require combination therapy including a thiazide diuretic such as hydrochlorothiazide (HCTZ) and an agent blocking the renin-angiotensin-aldosterone system. Current clinical practice usually limits the daily dose of HCTZ to 25 mg. This often leads to the necessity of using additional antihypertensive agents to control BP in a high proportion of patients. OBJECTIVES: To compare the efficacy of two doses of losartan (LOS)/HCTZ combinations in patients with uncontrolled ambulatory systolic hypertension after six weeks of treatment with LOS 100 mg/HCTZ 25 mg (LOS100/HCTZ25). METHODS: Following a two- to four-week washout period, subjects with a mean clinic sitting systolic BP of 160 mmHg or higher and a mean ambulatory daytime systolic BP (MDSBP) of 135 mmHg or higher on LOS100/HCTZ25 (n=105; 33 women and 72 men) were randomly assigned to receive LOS 150 mg/HCTZ 25 mg (group 1; n=53) or LOS 150 mg/HCTZ 37.5 mg (LOS150/HCTZ37.5, group 2; n=52). The primary end point was the difference in MDSBP reductions. RESULTS: At the end of the six-week treatment period, the respective additional decreases in MDSBP were 1.2 mmHg (P=0.335) on LOS 150 mg/HCTZ 25 mg and 5.6 mmHg (P<0.0001) on LOS150/HCTZ37.5 (difference of 4.4 mmHg; P=0.011). Daytime systolic ambulatory BP goal (lower than 130 mmHg) achievement tended to be higher (25% versus 17%; P=0.313) with LOS150/HCTZ37.5, while it was significantly higher (65% versus 43%; P=0.024) for mean daytime diastolic BP (lower than 80 mmHg). No deleterious metabolic changes were observed. CONCLUSIONS: In patients with uncontrolled systolic ambulatory hypertension receiving LOS100/HCTZ25, increasing both HCTZ and LOS dosages simultaneously to LOS150/HCTZ37.5 may be an effective strategy that does not affect metabolic parameters. PMID:20931100

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    V S Nade

    2015-01-01

    Conclusion: The results suggest that the cognitive enhancing effect of ACEI and ARBs may be due to inhibition of AChE or by regulation of antioxidant system or increase in formation of angiotensin IV.

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

    Science.gov (United States)

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

    2011-03-01

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

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

    Science.gov (United States)

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

    2011-01-01

    We examined the impact of fetal programming on the functional responses of renal angiotensin receptors. Fetal sheep were exposed in utero to betamethasone (BMX; 0.17 mg/kg) or control (CON) at 80–81 days gestation with full term delivery. Renal nuclear and plasma membrane fractions were isolated from 1.0–1.5 year old sheep for receptor binding and fluorescence detection of reactive oxygen species (ROS) or nitric oxide (NO). Mean arterial blood pressure and blood pressure variability were significantly higher in the BMX-exposed adult offspring versus control (CON) sheep. The proportion of nuclear AT1 receptors sensitive to losartan (LOS) was 2-fold higher [67 ± 6% vs. 27 ± 9%, p < 0.01] in BMX compared to control. In contrast, the proportion of AT2 sites was only one-third that of controls (BMX: 25 ± 11% vs. CON: 78 ± 4%, p < 0.01) with a similar reduction in sites sensitive to the Ang-(1-7) antagonist D-Ala7-Ang-(1-7) with BMX exposure. Functional studies revealed that Ang II stimulated ROS to a greater extent in BMX than control sheep (16 ± 3% vs. 6 ± 4%; P<0.05); however NO production to Ang II was attenuated in BMX (26 ± 7% vs. 82 ± 14%; P<0.05). BMX-exposure was also associated with a reduction in the Ang-(1-7) NO response [75 ± 8% vs. 131 ± 26%; P<0.05]. We conclude that altered expression of angiotensin receptor subtypes may be one mechanism whereby functional changes in NO- and ROS-dependent signaling pathways may favor the sustained increase in blood pressure evident in fetal programming. PMID:21220702

  16. 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...

  17. Telmisartan

    Science.gov (United States)

    ... to the rest of the body) and diabetic nephropathy (kidney disease in people with diabetes and high blood pressure). ... diuretics ('water pills') including spironolactone (Aldactone, in Aldactazide); lithium (Lithobid); and potassium supplements. Your doctor may need ...

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

    Directory of Open Access Journals (Sweden)

    Rene Barro-Soria

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

  19. Angiotensin receptor-mediated oxidative stress is associated with impaired cardiac redox signaling and mitochondrial function in insulin-resistant rats.

    Science.gov (United States)

    Vázquez-Medina, José Pablo; Popovich, Irina; Thorwald, Max A; Viscarra, Jose A; Rodriguez, Ruben; Sonanez-Organis, Jose G; Lam, Lisa; Peti-Peterdi, Janos; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M

    2013-08-15

    Activation of angiotensin receptor type 1 (AT1) contributes to NADPH oxidase (Nox)-derived oxidative stress during metabolic syndrome. However, the specific role of AT1 in modulating redox signaling, mitochondrial function, and oxidative stress in the heart remains more elusive. To test the hypothesis that AT1 activation increases oxidative stress while impairing redox signaling and mitochondrial function in the heart during diet-induced insulin resistance in obese animals, Otsuka Long Evans Tokushima Fatty (OLETF) rats (n = 8/group) were treated with the AT1 blocker (ARB) olmesartan for 6 wk. Cardiac Nox2 protein expression increased 40% in OLETF compared with age-matched, lean, strain-control Long Evans Tokushima Otsuka (LETO) rats, while mRNA and protein expression of the H₂O₂-producing Nox4 increased 40-100%. ARB treatment prevented the increase in Nox2 without altering Nox4. ARB treatment also normalized the increased levels of protein and lipid oxidation (nitrotyrosine, 4-hydroxynonenal) and increased the redox-sensitive transcription factor Nrf2 by 30% and the activity of antioxidant enzymes (SOD, catalase, GPx) by 50-70%. Citrate synthase (CS) and succinate dehydrogenase (SDH) activities decreased 60-70%, whereas cardiac succinate levels decreased 35% in OLETF compared with LETO, suggesting that mitochondrial function in the heart is impaired during obesity-induced insulin resistance. ARB treatment normalized CS and SDH activities, as well as succinate levels, while increasing AMPK and normalizing Akt, suggesting that AT1 activation also impairs cellular metabolism in the diabetic heart. These data suggest that the cardiovascular complications associated with metabolic syndrome may result from AT1 receptor-mediated Nox2 activation leading to impaired redox signaling, mitochondrial activity, and dysregulation of cellular metabolism in the heart.

  20. 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.

  1. An angiotensin II type 1 receptor blocker prevents renal injury via inhibition of the Notch pathway in Ins2 Akita diabetic mice.

    Science.gov (United States)

    Koshizaka, Masaya; Takemoto, Minoru; Sato, Seiya; Tokuyama, Hirotake; Fujimoto, Masaki; Okabe, Emiko; Ishibashi, Ryoichi; Ishikawa, Takahiro; Tsurutani, Yuya; Onishi, Shunichiro; Mezawa, Morito; He, Peng; Honjo, Satoshi; Ueda, Shiro; Saito, Yasushi; Yokote, Koutaro

    2012-01-01

    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. Commercial Telmisartan Tablets: A Comparative Evaluation with Innovator Brand Micardis

    OpenAIRE

    2010-01-01

    Purpose: Telmisartan is an angiotensin II receptor antagonist used in the management of hypertension. The solubility of Telmisartan in aqueous solutions is strongly pH-dependent. Five commercial tablets of telmisartan (40 and 80 mg) were compared with the reference formulation Micardis (Innovator brand of telmisartan molecule).Experimental: Dissolution tests were performed by employing USP type apparatus-II (Paddle type) at 75rpm using pH 1.2, 4.5 and 7.5 buffers as the dissolution media. The...

  3. Efecto de telmisartan sobre marcadores del remodelado óseo en pacientes hipertensos Telmisartan effect's on remodelling bone markers in hypertensive patients

    Directory of Open Access Journals (Sweden)

    J. L. Pérez-Castrillón

    2012-02-01

    remodelado aunque se observó un descenso de la glucosa en pacientes con niveles de vitamina D por encima de 20 ng/ml (135 ± 53 mg/dl vs 119 ± 39 mg/dl, p = 0,01. Los pacientes tratados con IECAS disminuyen los valores de tensión arterial sistólica pero la diastólica no muestra cambios. Conclusiones: Telmisartan tiene un efecto neutro a nivel de los marcadores del remodelado óseo.Introduction: The telmisartan is an angiotensin II receptor blocker (ARB with a few own characteristics that it allows us to obtain a few additional benefits. It displays the ability to act as a partial agonist of PPARgamma. On the other hand, PPAR gamma intervenes in the control of bone remodelling though with not concordant results. The objective of this study to value the effect of telmisartan on bone markers in hypertensive patients. Subjects: A sample of 31 hypertensive patients with hypertension were included. The dose of telmisartan was of 80 mg/24 h and the period of follow-up was 12 weeks. The control group included 32 hypertensive patients treated before with IECA (enalapril-20 mg/24 h - or quinapril - 40 mg/24 hours. The following parameters were determined P1NP, β-CTX, 25OHD and PTH , osteocalcin, insulin and adiponectin. Results: The patients treated with Telmisartan shown a significantly decrease in systolic blood pressure (156 ± 19 mmHg vs 133 ± 15 mmHg, p = 0.001 and diastolic blood pressure (92 ± 9 mmHgvs 82 ± 6 mmHg, p = 0.01 . Changes were not observed in other parameter, PTHi (48 ± 22 pg/ml vs 45 ± 22 pg/ml, p > 0.05 and 25-vitamin D (21 ± 10 ng/ml vs 25 ± 8 ng/ml, p > 0.05, CTX (0.195 ± 0.12 ng/ml vs 0.221 ± 0.13 ng/ml, p > 0.05, PINP (39 ± 20 ng/ml vs 40 ± 19 ng/ml, p > 0.05, osteocalcin (11 ± 9 ng/ml vs 11 ± 5 ng/ml, p > 0.05, glucose, adiponectin, insulin and HOMA. When the patients divided in two groups depending on the levels of vitamin D (insufficient and not insufficient, with a cut of 20 ng/ml, there was changes on bone markers but a decrease of the

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

    Directory of Open Access Journals (Sweden)

    Fenqing Shang

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

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

    Science.gov (United States)

    Shang, Fenqing; Zhang, Jiao; Li, Zhao; Zhang, Jin; Yin, Yanjun; Wang, Yaqiong; Marin, Traci L; Gongol, Brendan; Xiao, Han; Zhang, You-Yi; Chen, Zhen; Shyy, John Y-J; Lei, Ting

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

    Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid drug whose efficacy is limited by its hepatotoxicity. The aim of this study was to investigate the possible protective role of captopril (100 mg/kg/day, p.o. for seven days), an angiotensin converting enzyme inhibitor, and telmisartan (10 mg/kg/day p.o. for seven days), an angiotensin II receptor blocker with peroxisome proliferative receptor gamma (PPARγ) agonism, in a model of MTX (single dose 20 mg/kg i.p. at the fifth day) induced hepatotoxicity in rats. Results of the present study revealed MTX-induced hepatotoxicity as demonstrated by increased level of liver enzymes and confirmed by histopathology. Pretreatment with captopril or telmisartan produced a significant hepatic protection manifested as a significant (p < 0.05) decrease in serum levels of alanine transferase (ALT) and aspartate transferase (AST) and alkaline phosphatase (ALP) enzymes; hepatic malondialdehyde (MDA) and total nitrites and nitrates (NOx) levels; as well as a significant increase in hepatic superoxide dismutase (SOD) activity. In addition, there was a remarkable improvement in the histopathological features and a significant reduction in the expression of COX-2, iNOS and caspase-3 enzymes as compared with the MTX group. We recommend considering captopril/Telmisartan, if tolerated and not contraindicated, as preferable antihypertensive agents in patients receiving MTX in their chemotherapy protocols.

  7. Structural determinants for binding to angiotensin converting enzyme 2 (ACE2 and angiotensin receptors

    Directory of Open Access Journals (Sweden)

    Daniel eClayton

    2015-01-01

    Full Text Available Angiotensin converting enzyme 2 (ACE2 is a zinc carboxypeptidase involved in the renin angiotensin system (RAS and inactivates the potent vasopressive peptide angiotensin II (Ang II by removing the C-terminal phenylalanine residue to yield Ang1-7. This conversion inactivates the vasoconstrictive action of Ang II and yields a peptide that acts as a vasodilatory molecule at the Mas receptor and potentially other receptors. Given the growing complexity of RAS and level of cross-talk between ligands and their corresponding enzymes and receptors, the design of molecules with selectivity for the major RAS binding partners to control cardiovascular tone is an on-going challenge. In previous studies we used single β-amino acid substitutions to modulate the structure of Ang II and its selectivity for ACE2, AT1R and angiotensin type 2 (AT2R receptor. We showed that modification at the C-terminus of Ang II generally resulted in more pronounced changes to secondary structure and ligand binding, and here we further explore this region for the potential to modulate ligand specificity. In this study, 1 a library of forty-seven peptides derived from the C-terminal tetra-peptide sequence (-IHPF of Ang II was synthesised and assessed for ACE2 binding, 2 the terminal group requirements for high affinity ACE2 binding were explored by and N- and C-terminal modification, 3 high affinity ACE2 binding chimeric AngII analogues were then synthesized and assessed, 4 the structure of the full-length Ang II analogues were assessed by circular dichroism, and 5 the Ang II analogues were assessed for AT1R/AT2R selectivity by cell-based assays. Studies on the C-terminus of Ang II demonstrated varied specificity at different residue positions for ACE2 binding and four Ang II chimeric peptides were identified as selective ligands for the AT2 receptor. Overall, these results provide insight into the residue and structural requirements for ACE2 binding and angiotensin receptor

  8. Telmisartan ameliorates carbon tetrachloride-induced acute hepatotoxicity in rats.

    Science.gov (United States)

    Atawia, Reem T; Esmat, Ahmed; Elsherbiny, Doaa A; El-Demerdash, Ebtehal

    2017-02-01

    This study assessed the potential hepatoprotective effect of telmisartan (TLM), a selective angiotensin II type 1 (AT1 ) receptor blocker, on carbon tetrachloride (CCl4 )-induced acute hepatotoxity in rats. Intraperitoneal injection of male Wistar rats with CCl4 1 mL kg(-1) , 1:1 mixture with corn oil for 3 days increased serum alanine transaminase, aspartate transaminase, and alkaline phosphatase activities as well as total bilirubin, triglycerides and total cholesterol levels. This is in addition to the disrupted histological architecture in the CCl4 group. Rats receiving CCl4 and co-treated with TLM (3 and 10 mg kg(-1) , orally) showed ameliorated serum biochemical and histological changes almost to the control level. Nevertheless, rats treated with TLM (1 mg kg(-1) ) didn't show any significant changes compared to CCl4 intoxicated group. In addition, TLM rectified oxidative status disrupted by CCl4 intoxication. Interestingly, TLM protected against CCl4 -induced expressions of nuclear factor-κB, inducible nitric oxide synthase and cyclooxygenase-II, in a dose related manner. Moreover, TLM (3 and 10 mg kg(-1) ) significantly modified CCl4 -induced elevation in tumor necrosis factor-α and nitric oxide levels. Furthermore, TLM showed a marked decline in CD68+ cells stained areas and reduced activity of myeloperoxidase enzyme compared to CCl4 -intoxicated group. In conclusion, both doses of TLM (3 and 10 mg kg(-1) ) showed significant hepato-protective effects. However, TLM at a dose of 10 mg kg(-1) didn't show significant efficacy above 3 mg kg(-1) which is nearly equivalent to the human anti-hypertensive dose of 40 mg. Thus, may be effective in guarding against several hepatic complications due to its antioxidant and anti-inflammatory activities. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 359-370, 2017.

  9. 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...

  10. Telmisartan: a review of its use in cardiovascular disease prevention.

    Science.gov (United States)

    Frampton, James E

    2011-04-16

    Telmisartan (Micardis®, Pritor®), a well established angiotensin type 1 receptor antagonist, is indicated in the EU for the reduction of cardiovascular morbidity in patients with manifest atherothrombotic cardiovascular disease (CVD) or type 2 diabetes mellitus with documented target organ damage, as well as for the treatment of hypertension. In the pivotal ONTARGET trial, which enrolled ACE inhibitor-tolerant patients at high vascular risk, telmisartan 80 mg once daily added to existing, proven therapy was noninferior to ramipril 10 mg once daily (the gold standard cardioprotective ACE inhibitor) in terms of CVD prevention. Moreover, telmisartan was better tolerated than ramipril, as reflected in, for example, lower incidences of permanent treatment discontinuations due to cough and angioedema. The placebo-controlled TRANSCEND and PRoFESS studies provided supporting evidence for the (time-dependent) effectiveness of telmisartan in preventing cardiovascular events, although the drug appeared to have neither a beneficial nor a harmful impact on cardiovascular mortality. The TRANSCEND trial also demonstrated that telmisartan was well tolerated in ACE inhibitor-intolerant patients at high vascular risk. On the basis of these findings, telmisartan can be considered an effective treatment option for CVD prevention in patients at high vascular risk. Consideration may be given to prescribing the drug as an alternative to ramipril in patients who are able to tolerate ACE inhibitors and, potentially, instead of ramipril in patients who are unable to tolerate ACE inhibitors.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-14

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

  12. Combined Angiotensin Receptor Modulation in the Management of Cardio-Metabolic Disorders

    DEFF Research Database (Denmark)

    Paulis, Ludovit; Foulquier, Sébastien; Namsolleck, Pawel

    2016-01-01

    Cardiovascular and metabolic disorders, such as hypertension, insulin resistance, dyslipidemia or obesity are linked with chronic low-grade inflammation and dysregulation of the renin-angiotensin system (RAS). Consequently, RAS inhibition by ACE inhibitors or angiotensin AT1 receptor (AT1R......) blockers is the evidence-based standard for cardiovascular risk reduction in high-risk patients, including diabetics with albuminuria. In addition, RAS inhibition reduces the new onset of diabetes mellitus. Yet, the high and increasing prevalence of metabolic disorders, and the high residual risk even....... Therefore, a concept of dual AT1R/AT2R modulation emerges as a putative means for risk reduction in cardio-metabolic diseases. The approach employing simultaneous RAS blockade (AT1R) and RAS stimulation (AT2R) is distinct from previous attempts of double intervention in the RAS by dual blockade. Dual...

  13. Commercial Telmisartan Tablets: A Comparative Evaluation with Innovator Brand Micardis

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    Pratikkumar A. Patel,

    2010-09-01

    Full Text Available Purpose: Telmisartan is an angiotensin II receptor antagonist used in the management of hypertension. The solubility of Telmisartan in aqueous solutions is strongly pH-dependent. Five commercial tablets of telmisartan (40 and 80 mg were compared with the reference formulation Micardis (Innovator brand of telmisartan molecule.Experimental: Dissolution tests were performed by employing USP type apparatus-II (Paddle type at 75rpm using pH 1.2, 4.5 and 7.5 buffers as the dissolution media. The percentage cumulative release of Telmisartan was measured at 5, 10, 15, 30, 45, and 60 minutes espectively. The factor f2 of the FDA’s SUPAC Guide was applied tothe qualitative determination of ‘similarity’ between pairs of dissolution profiles of Micardis and those of each investigated formulation. Results:None of the commercial brands were similar to Micardis in dissolution profile at various pH points of testing. This was observed for both the strengths. Conclusion: Micardis tablets at both the strengths showed consistently higher release at pH 4.5 and 7.5 (i.e., pH conditions relevant to the intestine suggesting its pharmacokinetic activity could be perhaps superior to other marketed brands as it would release the drug consistently irrespective of pH.

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

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    Segura J

    2013-09-01

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

  15. 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

    . The score was used to predict renal/cardiovascular risk at baseline and at month 6 in the ARB treatment arm of the Reduction of Endpoints in NIDDM (noninsulin-dependent diabetes mellitus) with the Angiotensin II Antagonist Losartan (RENAAL) trial. The net risk difference at these time points indicated...

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

    Science.gov (United States)

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

    2015-11-01

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

  17. Thermal Analysis Study of Antihypertensive Drugs Telmisartan and Cilazapril

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    Refaat Ahmed Saber

    2014-05-01

    Full Text Available Purpose: The aim of the present work is to study the thermal analysis of telmisartan and cilazapril. Methods: Thermogravimetry (TGA, derivative thermogravimetry (DTG and differential thermal analysis (DTA were used through the work to achieve the thermal analysis study of some antihypertensive drugs, telmisartan and cilazapril. Results: The results led to thermal stability data and also to the interpretation concerning the thermal decomposition. Thermogravimetry data allowed determination of the kinetic parameters such as, activation energy and frequency factor. Conclusion: The simplicity, speed and low operational costs of thermal analysis justify its application in the quality control of pharmaceutical compounds for medications.

  18. 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....

  19. RP-HPLC estimation of ramipril and telmisartan in tablets

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    Kurade V

    2009-01-01

    Full Text Available A rapid high performance liquid chromatographic method has been developed and validated for the estimation of ramipril and telmisartan simultaneously in combined dosage form. A Genesis C18 column having dimensions of 4.6x250 mm and particle size of 5 µm in isocratic mode, with mobile phase containing a mixture of 0.01 M potassium dihydrogen phosphate buffer (adjusted to pH 3.4 using orthophosphoric acid: methanol:acetonitrile (15:15:70 v/v/v was used. The mobile phase was pumped at a flow rate of 1.0 ml/min and the eluents were monitored at 210 nm. The selected chromatographic conditions were found to effectively separate ramipril (R t : 3.68 min and telmisartan (R t : 4.98 min having a resolution of 3.84. The method was validated in terms of linearity, accuracy, precision, specificity, limit of detection and limit of quantitation. Linearity for ramipril and telmisartan were found in the range of 3.5-6.5 µg/ml and 28.0-52.0 µg/ml, respectively. The percentage recoveries for ramipril and telmisartan ranged from 99.09-101.64% and 99.45-100.99%, respectively. The limit of detection and the limit of quantitation for ramipril was found to be 0.5 µg/ml and 1.5 µg/ml respectively and for telmisartan was found to be 1.5 µg/ml and 3.0 µg/ml, respectively. The method was found to be robust and can be successfully used to determine the drug content of marketed formulations.

  20. Effect of angiotensin II receptor blocker on experimental periodontitis in a mouse model of Marfan syndrome.

    Science.gov (United States)

    Suda, Naoto; Moriyama, Keiji; Ganburged, Ganjargal

    2013-01-01

    Marfan syndrome is an autosomal dominant disease characterized by aneurysm and dilatation of the aortic root, tall stature, and ectopia lentis. These manifestations reflect excessive signaling of transforming growth factor beta (TGF-β). Moreover, cases are frequently associated with severe periodontitis, which is a chronic inflammation of the gingiva, periodontal ligament, and alveolar bone. Recently, angiotensin II receptor blockers (ARBs) were discovered to be an effective drug class that can prevent aortic aneurysm and dilation in Marfan syndrome by inhibiting TGF-β signaling. To investigate the effect of ARB on the progression of periodontitis, the application of a potent ARB, telmisartan, was examined in a mouse model of Marfan syndrome (MgΔ). Six-week-old male heterozygous MgΔ and wild-type mice were challenged with Porphyromonas gingivalis, which causes chronic periodontitis, with and without telmisartan application. After infection, alveolar bone resorption was measured by micro-computed tomography (μCT), and inflammatory cytokine levels were examined. Infection of Porphyromonas gingivalis induced alveolar bone resorption in both MgΔ and wild-type mice. The amount of resorption was significantly larger in the former than the latter. Immunoarray and enzyme-linked immunosorbent assay (ELISA) analyses demonstrated that interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) levels were significantly higher in infected MgΔ mice than infected wild-type mice. Telmisartan treatment significantly suppressed the alveolar bone resorption of infected MgΔ mice. Telmisartan also significantly decreased levels of TGF-β, IL-17, and TNF-α in infected MgΔ mice to levels seen in infected wild-type mice. This study suggests that ARB can prevent the severe periodontitis frequently seen in Marfan syndrome.

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

    DEFF Research Database (Denmark)

    Cibulskyte, Donata; pedersen, michael; Hørlyck, Arne;

    2007-01-01

    BACKGROUND: We have previously demonstrated renal enlargement in pigs treated with ciclosporin A (CsA) 10 mg/kg/day orally for 6 months. The aim of the study was to investigate the effect of oral CsA (10 mg/kg/day) for 12 months on kidney structure and function and the potential renoprotective role...... and 54, we measured body weight, mean arterial blood pressure (MAP), serum creatinine, whole blood trough CsA, plasma Ang II, haemoglobin and liver function parameters. Magnetic resonance imaging was used to estimate kidney length, volume, relative glomerular filtration rate (rGFR) and renal blood flow...... (RBF). Kidney tissue biopsies were used for conventional histological examination. RESULTS: Plasma Ang II levels were significantly higher during telmisartan treatment. Interstitial fibrosis and glomerulosclerosis occurred in both groups, but were attenuated in the telmisartan-treated pigs (P = 0...

  2. A fluorescence study on the interaction of telmisartan in triblock polymers pluronic P123 and F127

    Science.gov (United States)

    Mohanty, Maneesha Esther; Rao, Vaidya Jayathirtha; Mishra, Ashok Kumar

    2014-03-01

    Telmisartan is a poorly soluble drug used in treatment of hypertension. There is a recent interest to use pluronic for improving the solubility and bioavailability of these drugs. In this study the interaction of telmisartan with P123 and F127 has been carried out using steady state and time dependent fluorescence study. Quenching of telmisartan fluorescence by potassium iodide is controlled by interactions arising from collisions and complex formation. A comparison of the fluorescence of telmisartan in pluronics with the well understood fluorescence of 8-anilino-1-naphthalene-sulfonic acid, a known fluorescent molecular probe, indicates that telmisartan is generally present in a relatively polar microenvironment with restricted diffusive motion.

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

    Directory of Open Access Journals (Sweden)

    Takumi Hirata

    2013-01-01

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

  4. Telmisartan ameliorates cisplatin-induced nephrotoxicity by inhibiting MAPK mediated inflammation and apoptosis.

    Science.gov (United States)

    Malik, Salma; Suchal, Kapil; Gamad, Nanda; Dinda, Amit Kumar; Arya, Dharamvir Singh; Bhatia, Jagriti

    2015-02-05

    Nephrotoxicity is a major adverse effect of the widely used anticancer drug cisplatin. Oxidative stress, inflammation and apoptosis are implicated in the pathophysiology of cisplatin-induced acute renal injury. Moreover, cisplatin activates many signal transduction pathways involved in cell injury and death, particularly mitogen activated protein kinase (MAPK) pathway. With this background, we aimed to investigate the protective effect of telmisartan, a widely used antihypertensive drug, in cisplatin-induced nephrotoxicity model in rats. To accomplish this, male albino wistar rats (150-200 g) were divided into 6 groups: Normal, cisplatin-control, telmisartan (2.5, 5 and 10 mg/kg) and telmisartan per se treatment groups. Normal saline or telmisartan was administered orally to rats for 10 days and cisplatin was given on 7th day (8 mg/kg; i.p.) to induce nephrotoxicity. On 10th day, rats were killed and both the kidneys were harvested for biochemical, histopathological and molecular studies. Cisplatin injected rats showed depressed renal function, altered proxidant-antioxidant balance and acute tubular necrosis which was significantly normalized by telmisartan co-treatment. Furthermore, cisplatin administration activated MAPK pathway that caused tubular inflammation and apoptosis in rats. Telmisartan treatment significantly prevented MAPK mediated inflammation and apoptosis. Among the three doses studied telmisartan at 10 mg/kg dose showed maximum nephroprotective effect which could be due to maintenance of cellular redox status and inhibition of MAPK activation.

  5. Comparison of efficacy of telmisartan with losartan in patients of essential hypertension with cognitive impairment

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    Nitin Natthuji Puram

    2016-06-01

    Conclusions: Telmisartan is as effective as losartan in controlling blood pressure and improving cognitive function in hypertensive patients with cognitive impairment. [Int J Basic Clin Pharmacol 2016; 5(3.000: 702-706

  6. FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF TELMISARTAN

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    Kapil Chauhan*, Bharat Parashar, Abhishek Chandel and Varun Thakur

    2013-04-01

    Full Text Available ABSTRACT: The patients with sudden increase blood pressure have markedly reduced function ability and extremely restless, in such cases rapid onset of action is of prime importance. So the patients would be benefited from acute treatment by using Fast dissolving drug delivery system. Telmisartan is an Anti-hypertensive drug which is insoluble in water; hence the drug may be slowly or incompletely dissolves in the gastro-intestinal tract. So the rate of dissolution and therefore its bioavailability is less (bioavailability 42%. In the present study an attempt has been made to prepare. Fast Dissolving tablets of Telmisartan by using Superdisintegrants– Crosscarmellose Sodium, Doshion ,Sodium Starch Glycolate, level of addition to increase the rate of drug release from dosage form to increase the dissolution rate and hence its bioavailability. The tablets were prepared by Direct Compression methods and the prepared blend and tablets were evaluated for their physicochemical properties and In-vitro dissolution study. The evaluation studies were performed such as Weight Variation, Thickness, Hardness, Disintegrating Time, Wetting Time, and In-vitro Drug Release and Stability Study. The Disintegration time of Fast Dissolving tablets were increased by the addition of concentration of Superdisintegrants.

  7. In vitro interaction study of retinoic acid isomers with telmisartan and amlodipine by equilibrium dialysis method using UV spectroscopy

    Science.gov (United States)

    Varghese, Susheel John; Johny, Sojimol K.; Paul, David; Ravi, Thengungal Kochupappy

    2011-07-01

    The in vitro protein binding of retinoic acid isomers (isotretinoin and tretinoin) and the antihypertensive drugs (amlodipine and telmisartan) was studied by equilibrium dialysis method. In this study, free fraction of drugs and the % of binding of drugs in the mixture to bovine serum albumin (BSA) were calculated. The influence of retinoic acid isomers on the % of protein binding of telmisartan and amlodipine at physiological pH (7.4) and temperature (37 ± 0.5 °C) was also evaluated. The in vitro displacement interaction study of drugs telmisartan and amlodipine on retinoic acid isomers and also interaction of retinoic acid isomers on telmisartan and amlodipine were carried out.

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

    Directory of Open Access Journals (Sweden)

    Marc P Maillard

    2007-07-01

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

  9. Rationale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic

    Directory of Open Access Journals (Sweden)

    Volpe M

    2012-06-01

    lead to improvement in blood pressure control and aid compliance with long-term therapy, optimizing the management of this chronic condition.Keywords: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, triple therapy, hypertension

  10. Formulation and evaluation of multiparticulate drug delivery systems comprising telmisartan

    Directory of Open Access Journals (Sweden)

    Talasila E Gopala Krishna Murthy

    2015-01-01

    Full Text Available Telmisartan is poorly soluble in water, and the rate of dissolution, as well as bioavailability, is less. In the present study, an attempt has been made to improve the dissolution of the drug by coating the drug and carrier over sugar pellets. The solubility promoters such as alkalizes, binders and surfactants were selected to make the drug solution. The prepared pellets were evaluated for their physicochemical properties and in-vitro dissolution. The drug release rate was found to be more from the pellets coated with the coating solution containing the sodium hydroxide, Tween 80 and hydroxypropyl methylcellulose. The optimized pellet formulation was selected for stability study, and the in-vitro dissolution study showed that was no difference in percent of drug released between initial and 6 th month sample.

  11. Formulation development and evaluation of fast dissolving film of telmisartan

    Directory of Open Access Journals (Sweden)

    Vaishali Y Londhe

    2012-01-01

    Full Text Available Hypertension is a major cause of concern not just in the elderly but also in the youngsters. An effort was made to formulate a fast dissolving film containing telmisartan which is used in the treatment of hypertension with a view to improve the onset of action, therapeutic efficacy, patient compliance and convenience. The major challenge in formulation of oral films of telmisatran is that it shows very less solubility in the pH range of 3-9. Various film forming agents and polyhydric alcohols were evaluated for optimizing composition of fast dissolving films. Fast dissolving films using hydroxypropyl methylcellulose, polyvinyl alcohol, glycerol, sorbitol, menthol and an alkalizer were formulated using solvent casting method. Optimized formulations were evaluated for their weight, thickness, folding endurance, appearance, tensile strength, disintegration time and dissolution profile.

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

    Directory of Open Access Journals (Sweden)

    Heffernan M

    2016-06-01

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

  13. Comparative effectiveness analysis of amlodipine/renin-angiotensin system blocker combinations.

    Science.gov (United States)

    Ram, C Venkata S; Vasey, Joseph; Panjabi, Sumeet; Qian, Chunlin; Quah, Ruth

    2012-09-01

    A comparative effectiveness analysis of antihypertensive therapy amlodipine (AML) and angiotensin receptor blocker (ARB) fixed- and loose-dose combinations (FDCs and LDCs) in achieving blood pressure (BP) reduction and Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) goal attainment was made using retrospective electronic medical record (EMR) data. Treatment goal rates ranged from 35.0% for LDC AML/losartan to 45.7% for FDC AML/olmesartan (OM). FDC AML/OM achieved significantly greater reductions in systolic BP than FDC AML/benazepril (BEN), FDC AML/valsartan (VAL), and LDC AML/ARBs, respectively, and significantly greater reductions in diastolic BP than FDC AML/VAL and LDC therapy, respectively. Compared with patients treated with AML/OM, patients prescribed AML/VAL and LDC AML/ARB were significantly less likely to attain JNC 7 BP goal. Among subpopulations, AML/OM yielded higher rates of goal attainment among both African Americans and obese/overweight patients relative to AML/VAL and combined LDCs. Switchers from monotherapy with AML, OM, or VAL to AML/OM were significantly more likely to attain JNC 7 goals than those switching to AML/VAL or AML/BEN.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  15. Pharmacokinetic drug-drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel-ethinyl estradiol in healthy subjects.

    Science.gov (United States)

    Gan, Lu; Jiang, Xuemin; Mendonza, Anisha; Swan, Therese; Reynolds, Christine; Nguyen, Joanne; Pal, Parasar; Neelakantham, Srikanth; Dahlke, Marion; Langenickel, Thomas; Rajman, Iris; Akahori, Mizuki; Zhou, Wei; Rebello, Sam; Sunkara, Gangadhar

    2016-01-01

    LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 μg single dose (n = 24) in three separate open-label, single-sequence studies in healthy subjects. Pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan), metformin, and levonorgestrel-ethinyl estradiol were assessed. Omeprazole did not alter the AUCinf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the Cmax of sacubitril, and 11% and 13% decreases in AUCinf and Cmax of valsartan were observed. Co-administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUCtau,ss and Cmax,ss of metformin were decreased by 23%. Co-administration of LCZ696 with levonorgestrel-ethinyl estradiol had no effect on the pharmacokinetics of ethinyl estradiol and LBQ657 or AUCinf of levonorgestrel. The Cmax of levonorgestrel decreased by 15%, and AUCtau,ss and Cmax,ss of valsartan decreased by 14% and 16%, respectively. Co-administration of LCZ696 with omeprazole, metformin, or levonorgestrel-ethinyl estradiol was not associated with any clinically relevant pharmacokinetic drug interactions.

  16. Efficacy and Safety of Combination Therapy Consisting of Angiotensin II Type 1 Receptor Blocker, Calcium Channel Blocker and Hydrochlorothiazide in Patients With Hypertension

    Science.gov (United States)

    Shiga, Yuhei; Miura, Shin-ichiro; Motozato, Kota; Yoshimine, Yuka; Norimatsu, Kenji; Arimura, Tadaaki; Koyoshi, Rie; Morii, Joji; Kuwano, Takashi; Inoue, Ken; Shirotani, Tetsuro; Fujisawa, Kazuaki; Matsunaga, Eiyu; Saku, Keijiro

    2017-01-01

    Background Many patients continue to have high blood pressure (BP) even after treatment with high-dose (H)-angiotensin II type 1 receptor blocker (ARB)/calcium channel blocker (CCB) or middle-dose (M)-ARB/CCB/hydrochlorothiazide (HCTZ). Methods Thirty-two hypertensive patients who had the use of H-ARB/CCB or M-ARB/CCB/HCTZ were enrolled in this study. We applied a changeover with a switch to H-ARB (telmisartan 80 mg/day)/CCB (amlodipine 5 mg/day or nifedipine CR 40 mg/day)/HCTZ (12.5 mg/day). Results Systolic BP (SBP) and diastolic BP (DBP) were significantly decreased in all patients and in the H-ARB/CCB and M-ARB/CCB/HCTZ groups after 3 months. Percentage (%) of patients who reached the target BP after 3 months (72%) in all patients was significantly higher than that at 0 months (19%). There were no serious adverse effects in any of the patients. Conclusions Combination therapy with H-ARB/CCB/HCTZ was associated with a significant reduction of BP. PMID:28090225

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

    Science.gov (United States)

    Kimura, Hideki; Mikami, Daisuke; Kamiyama, Kazuko; Sugimoto, Hidehiro; Kasuno, Kenji; Takahashi, Naoki; Yoshida, Haruyoshi; Iwano, Masayuki

    2014-11-14

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

  18. Solubilization of the poorly water soluble drug, telmisartan, using supercritical anti-solvent (SAS) process.

    Science.gov (United States)

    Park, Junsung; Cho, Wonkyung; Cha, Kwang-Ho; Ahn, Junhyun; Han, Kang; Hwang, Sung-Joo

    2013-01-30

    Telmisartan is a biopharmaceutical classification system (BCS) class II drug that has extremely low water solubility but is freely soluble in highly alkalized solutions. Few organic solvents can dissolve telmisartan. This solubility problem is the main obstacle achieving the desired bioavailability. Because of its unique characteristics, the supercritical anti-solvent (SAS) process was used to BCS class II drug in a variety of ways including micronization, amorphization and solid dispersion. Solid dispersions were prepared using hydroxypropylmethylcellulose/polyvinylpyrrolidone (HPMC/PVP) at 1:0.5, 1:1, and 1:2 weight ratios of drug to polymer, and pure telmisartan was also treated using the SAS process. Processed samples were characterized for morphology, particle size, crystallinity, solubility, dissolution rate and polymorphic stability. After the SAS process, all samples were converted to the amorphous form and were confirmed to be hundreds nm in size. Solubility and dissolution rate were increased compared to the raw material. Solubility tended to increase with increases in the amount of polymer used. However, unlike the solubility results, the dissolution rate decreased with increases in polymer concentration due to gel layer formation of the polymer. Processed pure telmisartan showed the best drug release even though it had lower solubility compared to other solid dispersions; however, because there were no stabilizers in processed pure telmisartan, it recrystallized after 1 month under severe conditions, while the other solid dispersion samples remained amorphous form. We conclude that after controlling the formulation of solid dispersion, the SAS process could be a promising approach for improving the solubility and dissolution rate of telmisartan.

  19. Effects of calcium channel blockers on proteinuria in patients with diabetic nephropathy.

    Science.gov (United States)

    Toto, Robert D; Tian, Min; Fakouhi, Kaffa; Champion, Annette; Bacher, Peter

    2008-10-01

    Diabetic nephropathy management should include the use of an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker with additional antihypertensive medications to reduce proteinuria and cardiovascular events. Some studies suggest that adding a nondihydropyridine rather than a dihydropyridine calcium channel blocker (CCB) may more effectively lower proteinuria. We hypothesized that a trandolapril/verapamil SR (T/V) fixed-dose combination (FDC) was superior to a benazepril/amlodipine (B/A) FDC for reducing albuminuria in 304 hypertensive diabetic nephropathy patients when treated for 36 weeks. No statistically significant differences were observed between groups in the primary end point; adjusted percentage change in urinary albumin/creatinine ratio (UACR), which increased (mean T/V, 29.29%; mean B/A, 8.49%; difference, 20.80%; P=.34); or in change in absolute UACR, which decreased (mean [g/g] T/V, -0.11; mean [g/g] B/A, -0.08; difference -0.03; P=.78). There were significant reductions in log UACR (mean change in T/V, -0.28; P<.01; mean change in B/A, -0.31; P<.001) and diastolic blood pressure in both groups and in systolic blood pressure in the B/A group. T/V was not superior to B/A for reducing UACR. Both ACEI/CCB FDCs may reduce albuminuria; in the case of T/V, this appears to be independent of systolic blood pressure reduction in patients who had previously been treated and had baseline blood pressure levels of 142/77 mm Hg.

  20. Prevention of metabolic disorders with telmisartan and indapamide in a Chinese population with high-normal blood pressure.

    Science.gov (United States)

    Peng, Jie; Zhao, Yingxin; Zhang, Hua; Liu, Zhendong; Wang, Zhihao; Tang, Mengxiong; Zhong, Ming; Lu, Fanghong; Zhang, Wei

    2015-02-01

    High-normal blood pressure is considered a precursor of stage 1 hypertension that is associated with metabolic disorders. This study aims to investigate whether the pharmacologic treatment of high-normal blood pressure affects metabolism, especially in abdominally obese individuals, and the pharmacoeconomics of two antihypertensive agents, telmisartan and indapamide. Subjects with high-normal blood pressure were randomly assigned to receive telmisartan, indapamide or placebo for 3 years. All the subjects were instructed to modify their lifestyle to reduce blood pressure throughout the study. A total of 221 subjects were randomly assigned to telmisartan, 213 to indapamide and 230 to placebo. After the 3-year intervention, blood pressure was lower in the telmisartan and indapamide groups (P0.05). The percentage of subjects with metabolic syndrome was significantly decreased in the telmisartan and indapamide groups (Phigh-normal blood pressure with telmisartan and indapamide appeared to be feasible and reduced the risk of metabolic syndrome. Telmisartan was more effective, whereas indapamide had better pharmacoeconomic benefits.

  1. FIRST ORDER DERIVATIVE SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS ESTIMATION OF TELMISARTAN AND CHLORTHALIDONE IN BULK AND PHARMACEUTICAL DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Parmar Kreny E.

    2013-03-01

    Full Text Available A simple, precise, and accurate method was developed for the estimation of Telmisartan (TEL and Chlorthalidone (CHL in bulk and pharmaceutical dosage form using first order derivative spectrophotometry. Wavelength selected for quantitation were 264.85nm for Telmisartan (zero crossing point of Chlorthalidone and 222.38nm for Chlorthalidone(zero crossing point of Telmisartan. The method was validated with respect to linearity, accuracy, precision, limit of detection and limit of quantitation in accordance with the International Conference on Harmonisation (ICH guidelines. Linearity was observed in concentration range of 8-48 µg/ml for Telmisartan and 2.5-15 µg/ml for Chlorthalidone. The limit of detection and limit of quantitation were found to be 0.234µg/ml and 0.712 µg/ml for Telmisartan and 0.102 µg/ml and 0.309 µg/ml for Chlorthalidone. The percentage recovery of Telmisartan and Chlorthalidone was found to be 99.26% and 99.36% respectively. The % R.S.D. values for intra-day and inter-day precision study were <1.0%, confirming that the method was sufficiently precise. The method can be successfully employed for the simultaneous estimation of Telmisartan and Chlorthalidone in pharmaceutical formulations.

  2. Differential surface properties of commercial crystalline telmisartan samples.

    Science.gov (United States)

    Laad, Preksha; Shete, Ganesh; Modi, Sameer R; Bansal, Arvind Kumar

    2013-05-13

    The aim of the present study was to investigate differences in surface chemistry of commercially available telmisartan (TMS) samples in Indian market and to correlate them to the surface molecular environment. Comprehensive characterization of material properties of four TMS samples from different sources showed that all samples exhibited same polymorphic form, but different particle shape, particle size distribution, surface energetics and surface chemistry. Wettability and surface free energy were determined using sessile drop contact angle technique. TMS samples exhibited significant variations in their wetting behavior. The role of crystal shape, particle size distribution, surface energetics and surface chemistry in controlling TMS powder wettability was collectively explored by contact angle experiments. Evaluation of work of adhesion (Wa), immersion (Wi) and spreading (Ws) indicated that samples had differential wetting behavior. The surface chemistry was elucidated by X-ray photoelectron spectroscopy (XPS). The surface polarity index was determined by XPS and expressed as (oxygen+nitrogen)-to-(carbon) atomic concentration ratio. It was found to be different for all four TMS samples. Crystal morphology of TMS polymorph A was predicted using Bravais-Friedel Donnay-Harker (BFDH) method. Molecular lipophilic surface potential (MLSP) data for TMS showed the varied surface lipophilic environment throughout the molecule. Hence it can be concluded that the differential abundance of surface elements play an important role in controlling the biopharmaceutical performance of TMS powder samples.

  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. Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment : data from the CHARM-study programme

    NARCIS (Netherlands)

    Damman, Kevin; Solomon, Scott D.; Pfeffer, Marc A.; Swedberg, Karl; Yusuf, Salim; Young, James B.; Rouleau, Jean L.; Granger, Christopher B.; McMurray, John J. V.

    2016-01-01

    Aims We investigated the association between worsening renal function (WRF) that occurs during renin-angiotensin-aldosterone system inhibition initation and outcome in heart failure (HF) patients with preserved ejection fraction (HFPEF) and compared this with HF patients with reduced ejection fracti

  5. Protective effect of telmisartan on rats with renal failure and its mechanism

    Institute of Scientific and Technical Information of China (English)

    Zhi-Kui Wang; Zhen-Ying Liu; Hai-Bo Yu

    2015-01-01

    Objective:To study the protective effect of telmisartan on rats with renal failure and its mechanism. Methods:60 Wistar rats were chosen as study objective, and were divided into 4 groups randomly:15 in group A (sham operation group), 15 in group B (model group), 15 in group C (telmisartan group) and 15 in group D (telmisartan+GW9962 group). The difference of survival rate, blood-urine biochemical indexes, renal pathological change, and the expression level of PPARγ and nNOS were compared. Results:After 12 weeks, the survival rate of group A was 93.33%(14/15), that of group B was 46.67%(7/15), that of group C was 86.67%(13/15), that of group D was 60.00%(9/15), and the difference among 4 groups had statistical significance (P0.05);after 3 weeks, 6 weeks and 12 weeks, these difference was statistical significant (P<0.05). The difference of blood-urine biochemical indexes, that of renal pathological change, and that of the expression level of PPAR毭and nNOS was statistical significant (P<0.05). Conclusions:Telmisartan has protective effect on renal failure caused by 5/6 nephrectomy, which might be relative to the expression level of PPARγ and nNOS.

  6. DETERMINATION OF TELMISARTAN IN PHARMACEUTICAL FORMULATIONS BY REVERSE PHASE-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

    Directory of Open Access Journals (Sweden)

    Manoj S. Charde

    2012-05-01

    Full Text Available A simple, sensitive and reproducible reverse-phase high performance liquid chromatographic (RP-HPLC method has been developed for the quantitative estimation of Telmisartan (TELM in the pharmaceutical formulations. Chromatographic separation was achieved on a 250 × 4.6 mm, 5μ, Waters symmetry column. The flow rate was 1 ml/min and eluent was monitored by absorbance at 230 nm using a mixture of Methanol and Acetonitrile (pH 3.0±0.01 in the ratio of 30:70 (v/v. The retention time of Telmisartan was found to be 7.9 min. Calibration plots were linear in the concentration range of 10-50 μg/ml for Telmisartan with correlation coefficient (R2 0.999. The proposed method was validated by testing its linearity, recovery, specificity, system suitability, precision (Interday, intraday, analyst and instrument precision, robustness and LOD/LOQ values and it was successfully employed for the determination of Telmisartan in pharmaceutical tablet formulations.

  7. Captopril and telmisartan treatments attenuate cadmium-induced testicular toxicity in rats.

    Science.gov (United States)

    Fouad, Amr A; Jresat, Iyad

    2013-04-01

    The possible protective effect of captopril, an angiotensin-converting enzyme inhibitor, vs. telmisartan, an angiotensin II-receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor-α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium-induced expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand, and caspase-3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium.

  8. Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate the effects of telmisartan on the blood glucose, blood lipid, blood insulin, and insulin resistance in the hypertensive patients with dyslipidemia, and also its effect on controlling blood pressure. Patients and Methods A total of 96hypertensive patients (34 females, 62 males) with dyslipidemia were included (mean age 51.2±9.6, range 42-65 years). Patients were randomized to receive either telmisartan 80 mg/day (n=46) or enalapril 10 mg/day (n=50) for 6 months. The levels of blood pressure (BP), heart rate (HR), and biochemical data were measured before therapy and at the end of the 3-month treatment and 6-month treatment, respectively. Meanwhile, insulin resistance was evaluated by using a homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-IS). Results In the telmisartan group, the mean blood pressure was obviously lower than that of pre-therapy (P<0.05), and the levels of triglyceride (TG), HOMA-IR, and HOMA-IS were all obviously lower than those of pre-therapy and of the enalapril group at the end of the 3-month-treatment period (P<0.05). After 6 months of treatment, the levels of TG, HOMA-IR, and HOMA-IS in the telmisartan group were significantly lower in comparison with those of pre-therapy, the enalapril group (P<0.01), and 3-month-treatment (P<0.05). Post-prandial12 hour blood glucose (P2HBG) in the telmisartan group decreased significantly after 6-month treatment compared with that of pre-therapy and the enalapril group (P<0.05). The level of high density lipoprotein (HDL) cholesterol was significantly higher after 6-month treatment in the telmisartan group than with pre-therapy and the enalapril group(P<0.05). Conclusions Telmisartan could not only control blood pressure steadily and effectively, but also decrease blood TG, increase HDL cholesterol and insulin sensitivity, and lower insulin resistance.

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

    DEFF Research Database (Denmark)

    He, Hongbo; Yang, Dachun; Ma, Liqun

    2010-01-01

    -gamma expression, whereas neither candesartan nor losartan affected PPAR-delta expression. In vivo, long-term administration of telmisartan significantly reduced visceral fat and prevented high-fat diet-induced obesity in wild-type mice and hypertensive rats but not in PPAR-delta knockout mice. Administration...... and increased uncoupling protein 2 and 3 expression in skeletal muscle in wild-type mice but not in PPAR-delta knockout mice. We conclude that telmisartan prevents adipogenesis and weight gain through activation of PPAR-delta-dependent lipolytic pathways and energy uncoupling in several tissues.......)-delta-dependent pathways in several tissues. In vitro, telmisartan significantly upregulated PPAR-delta expression in 3T3-L1 preadipocytes in a time- and dose-dependent manner. Other than enhancing PPAR-delta expression by 68.2+/-17.3% and PPAR-delta activity by 102.0+/-9.0%, telmisartan also upregulated PPAR...

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

    Science.gov (United States)

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

    2016-08-01

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

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

    OpenAIRE

    2007-01-01

    Abstract Background The Study of Micardis (telmisartan) in Overweight/Obese patients with Type 2 diabetes and Hypertension (SMOOTH) compared hydrochlorothiazide (HCTZ) plus telmisartan or valsartan fixed-dose combination therapies on early morning blood pressure (BP), using ambulatory BP monitoring (ABPM). Methods SMOOTH was a prospective, randomized, open-label, blinded-endpoint, multicentre trial. After a 2- to 4-week, single-blind, placebo run-in period, patients received once-daily telmis...

  12. 血管紧张素AT4受体对学习和记忆作用的研究进展%Advances of angiotensin receptor AT4 in learning and memory

    Institute of Scientific and Technical Information of China (English)

    段立晖; 何月

    2012-01-01

    血管紧张素(angiotensin,Ang)AT4受体在大脑中作用的研究受到越来越多的重视.该受体广泛分布于哺乳动物的海马、新皮质、小脑等部位,可被Ang Ⅳ激活,与学习和记忆功能有关.文中就AT4受体在学习、记忆功能中的研究进展作一综述.%There is increasing interest in the role of the brain angiotensin receptor subtype AT 4 in cognitive processing. This receptor subtype is activated by angiotensin , is heavily distributed in the mammalian hippocampus , neocortex and cerebellum , and has been linked with a learning and memory function .

  13. Angiotensin II type 2 receptor expression after vascular injury: differing effects of angiotensin-converting enzyme inhibition and angiotensin receptor blockade.

    Science.gov (United States)

    Barker, Thomas A; Massett, Michael P; Korshunov, Vyacheslav A; Mohan, Amy M; Kennedy, Amy J; Berk, Bradford C

    2006-11-01

    It has been suggested that the effects of angiotensin II type 1 receptor (AT1R) blockers are in part because of angiotensin II type 2 receptor (AT2R) signaling. Interactions between the AT2R and kinins modulate cardiovascular function. Because AT2R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT1R blocker valsartan and the ACE inhibitor benazepril require AT2R signaling through the bradykinin 1 and 2 receptors (B1R and B2R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT2R inhibitor), valsartan+des-arg9-[Leu8]-bradykinin (B1R inhibitor), valsartan+HOE140 (B2R inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT2R, B1R, or B2R in the presence of valsartan prevented the reduction seen with valsartan alone. B2R blockade inhibited the effect of benazepril. Injury increased AT1R, AT2R, B1R, and B2R expression. Treatment with valsartan but not benazepril significantly increased intima AT2R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT2R, B1R, and B2R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT2R, B1R, and B2R. Results suggest that AT2R expression and increased cGMP represent a molecular mechanism that differentiates AT1R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril.

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

    OpenAIRE

    Srinivasan, V.; Sivaramakrishnan, H.; Karthikeyan, B

    2016-01-01

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

  15. Efficacy and safety of telmisartan vs. losartan in control of mild-to-moderate hypertension: a multicentre, randomised, double-blind study.

    Science.gov (United States)

    Zhu, J R; Bai, J; Cai, N S; Tang, B; Fan, W H; Guo, J Z; Ke, Y N; Guo, J X; Sheng, L H; Lu, Z Y; Cheng, N N

    2004-12-01

    This multicentre, randomised, double-blind, double-dummy, parallel-group study compared the efficacy and safety of telmisartan with those of losartan after 8 weeks' treatment. In total, 330 patients with mild-to-moderate hypertension (systolic blood pressure [SBP] mmHg; diastolic blood pressure [DBP] 95-109 mmHg) were randomly assigned to receive once-daily treatment with telmisartan 40 mg (n = 164) or losartan 50 mg (n = 166). After 4 weeks' treatment, if a patient's DBP was > or = 90 mmHg, the dose was increased to telmisartan 80 mg or losartan 100 mg, respectively. The results show that mean trough seated blood pressure was reduced significantly more in the telmisartan group than that in the losartan group (SBP 12.5 mmHg vs. 9.4 mmHg, p = 0.037; DBP 10.9 mmHg vs. 9.3 mmHg, p = 0.030). The overall DBP response rate (reduction from baseline in mean seated DBP > or = 10 mmHg and/or a mean seated DBP mmHg) at the end of the study in the telmisartan group was higher than that in losartan group (70.1% vs. 58.7%, p = 0.020). At both the low and high doses, the DBP response rates for telmisartan were significantly higher than those for losartan (telmisartan 40 mg vs. losartan 50 mg: 46.3% vs. 32.5%, p = 0.010; telmisartan 80 mg vs. losartan 100 mg: 79.3% vs. 65.3%, p = 0.008). Adverse events with the two treatments were comparable (telmisartan vs. losartan 23.2% vs. 22.9%, p = 0.952). Most events were mild in intensity and abated within 72 h. Thus, telmisartan 40 mg or 80 mg administered once daily can reduce SBP and DBP effectively and safely.

  16. Reversible Fetal Renal Impairment following Angiotensin Receptor Blocking Treatment during Third Trimester of Pregnancy: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Tal Saar

    2016-01-01

    Full Text Available Background. Late pregnancy usage of angiotensin converting enzyme inhibitors (ACE-I and angiotensin II receptor blockers (ARB may cause severe oligohydramnios due to fetal renal impairment. Affected neonates will often suffer from fatal, renal, and respiratory failure. Case. A 39-year-old multigravida admitted due to anhydramnios secondary to valsartan (ARB exposure at 30 weeks’ gestation. Following secession of treatment amniotic fluid volume returned to normal. Delivery was induced at 34 weeks’ gestation following premature rupture of membranes and maternal fever. During the two-year follow-up, no signs of renal insufficiency were noted. Conclusions. This description of reversible fetal renal damage due to ARB intake during pregnancy is the first to show no adverse renal function in a two-year follow-up period. This case may help clinicians counsel patients with pregnancies complicated by exposure to these drugs.

  17. Reversible Fetal Renal Impairment following Angiotensin Receptor Blocking Treatment during Third Trimester of Pregnancy: Case Report and Review of the Literature

    Science.gov (United States)

    Saar, Tal; Levitt, Lorinne

    2016-01-01

    Background. Late pregnancy usage of angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) may cause severe oligohydramnios due to fetal renal impairment. Affected neonates will often suffer from fatal, renal, and respiratory failure. Case. A 39-year-old multigravida admitted due to anhydramnios secondary to valsartan (ARB) exposure at 30 weeks' gestation. Following secession of treatment amniotic fluid volume returned to normal. Delivery was induced at 34 weeks' gestation following premature rupture of membranes and maternal fever. During the two-year follow-up, no signs of renal insufficiency were noted. Conclusions. This description of reversible fetal renal damage due to ARB intake during pregnancy is the first to show no adverse renal function in a two-year follow-up period. This case may help clinicians counsel patients with pregnancies complicated by exposure to these drugs. PMID:27672462

  18. Effect of telmisartan vs. ramipril on 'dipping' status and blood pressure variability: pooled analysis of the PRISMA studies.

    Science.gov (United States)

    Gosse, Philippe; Schumacher, Helmut

    2014-02-01

    A retrospective pooled analysis of the 'Prospective, Randomized Investigation of the Safety and Efficacy of MICARDIS vs. Ramipril Using ABPM' studies conducted in Europe and South Africa (PRISMA I) and in the United States of America and Canada (PRISMA II) was carried out to investigate the effects of telmisartan and ramipril on dipper status (extreme dippers, dippers, non-dippers, risers/reverse dippers), and blood pressure (BP) variability in 1279 patients (with normal sleeping patterns and valid 24-h ambulatory BP monitoring recordings at baseline and end point). After 14 weeks' treatment, telmisartan had a greater systolic BP (SBP) reduction and higher smoothness index in all four dipper groups compared with ramipril. In addition, the tendency toward dipping was significantly higher in patients treated with) telmisartan than ramipril (P=0.032; odds ratio for telmisartan vs. ramipril: 1.27 (95% confidence interval: 1.102-1.58)). In patients with an early morning SBP surge 35 mm Hg, telmisartan treatment was associated with significantly greater reductions from baseline in the night-time low mean, early morning mean and early morning SBP surge compared with ramipril (P=0.026, P<0.0001 and P=0.0006, respectively). In this retrospective analysis, telmisartan was shown to normalize the circadian BP pattern to a dipper profile in a larger proportion of patients than ramipril, and reduce early-morning SBP surge in high-risk patients, indicative of a cardioprotective effect. These findings need to be confirmed in long-term prospective trials and observational studies.

  19. Myokardinfarkt und Beta-Blocker

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    Stühlinger H-G

    2003-01-01

    Full Text Available Im Rahmen eines akuten koronaren Syndroms (akuter Herzinfarkt, Angina pectoris kommt es, aufgrund eines Ungleichgewichtes zwischen Angebot und Bedarf, zu einem akuten Mangel an Sauerstoff im Herzmuskel. Ursache ist eine reduzierte Sauerstoffzufuhr durch verengte bzw. verschlossene Gefäße. Bis zur Behebung der Ursache vergehen oft mehrere Stunden. In dieser Phase muß - durch Verminderung des Sauerstoffbedarfs im Herzmuskel - eine Verlangsamung der Nekroseentwicklung erreicht werden. Das Ausmaß der Nekrose wird reduziert, somit die für die Langzeitprognose wichtige Linksventrikelfunktion verbessert. Eine Verminderung des Sauerstoffbedarfs erreicht man durch kontrollierte Frequenzsenkung mittels intravenöser Beta-Blockade. In optimaler Weise wird diese Methode durch die Anwendung eines kardioselektiven Beta-Blockers mit kurzer Halbwertszeit durchgeführt. Beta-Blocker haben nicht nur auf die Nekroseentwicklung, sondern auch auf die Inzidenz von Rhythmusstörungen - besonders in der Akutphase - Auswirkungen. Vor allem die mit dieser therapeutischen Maßnahme verbundene Reduktion von Kammerflimmern ist von großer Bedeutung.

  20. Angiotensin System Blockade Combined With Calcium Channel Blockers Is Superior to Other Combinations in Cardiovascular Protection With Similar Blood Pressure Reduction: A Meta-Analysis in 20,451 Hypertensive Patients.

    Science.gov (United States)

    Chi, Chen; Tai, Chenhui; Bai, Bin; Yu, Shikai; Karamanou, Marianna; Wang, Jiguang; Protogerou, Athanase; Blacher, Jacques; Safar, Michel E; Zhang, Yi; Xu, Yawei

    2016-08-01

    The authors aimed to investigate the superiority of angiotensin system blockade (angiotensin-converting enzyme [ACE] inhibitor/angiotensin receptor blocker [ARB]) plus a calcium channel blocker (CCB) (A+C) over other combination therapies in antihypertensive treatment. A meta-analysis in 20,451 hypertensive patients from eight randomized controlled trials was conducted to compare the A+C treatment with other combination therapies in terms of blood pressure (BP) reduction, clinical outcomes, and adverse events. The results showed that BP reduction did not differ significantly among the A+C therapy and other combination therapies in systolic and diastolic BP (P=.87 and P=.56, respectively). However, A+C therapy, compared with other combination therapies, achieved a significantly lower incidence of cardiovascular composite endpoints, including cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.70-0.91; Pother combinations (Pother combination therapies (P=.34) but presented a significantly lower incidence of serious adverse events (RR, 0.85; 95% CI, 0.73-0.98; P=.03). In conclusion, A+C therapy is superior to other combinations of antihypertensive treatment as it shows a lower incidence of cardiovascular events and adverse events, while it has similar effects in lowering BP and preserving renal function.

  1. Effect of telmisartan combined with levocarnitine on nutritional status in patients with peritoneal dialysis

    Institute of Scientific and Technical Information of China (English)

    Jin-Xiu Cheng; Ji-Fang Lu; Sheng-Jun Liu; Zhi-Feng Wei; Hua Liu; Li-Kun Sun

    2016-01-01

    Objective:To explore the effect of telmisartan combined with levocarnitine on the nutritional status in patients with peritoneal dialysis (PD).Methods: A total of 80 patients with chronic renal failure (CRF) who were admitted in our hospital from November, 2011 to January, 2014 were included in the study and randomized into the treatment group and the control group. The patients in the two groups were performed with PD. The patients in the treatment group were given levocarnitine oral solution, 10 mL/time, 3 times/d, and telmisartan, 80 mg/time, 1 time/d. The patients in the control group were only given levocarnitine oral solution, 10 mL/time, 3 times/d. The patients in the two groups were continuously administrated for 24 weeks. A volume of 5 mL morning fasting elbow venous blood was extracted before and after treatment. The automatic biochemical analyzer was used to detect Hb, Alb, PA, TG, and TC. TSF and MAC were measured. MAMA was calculated. SGA was used to evaluate the nutrition.Results:After treatment, Hb, Alb, and PA in the treatment group were significantly elevated, while TG was significantly reduced when compared with before treatment (P0.05), those after treatment in the control group were not significantly different from those before treatment (P>0.05), and those in the treatment group were significantly superior to those in the control group (P0.05), and those in the treatment group were significantly superior to those in the control group (P<0.05). Conclusions: Telmisartan combined with levocarnitine in application of PD patients can effectively improve the malnutrition, and correct the lipid metabolism disorder to delay the loss of residual renal function.

  2. Are ACE-inhibitors or ARB's still needed for cardiovascular prevention in high risk patients? Insights from profess and transcend.

    Science.gov (United States)

    Van Mieghem, W; Billiouw, J M; Brohet, C; Dupont, A G; Gazagnes, M D; Heller, F; Krzesinski, J M; Missault, L; Persu, A; Piérard, L; Rottiers, R; Vanhooren, G; Vervaet, P; Herman, A G

    2010-01-01

    The HOPE and EUROPA clinical studies have shown that treatment with the angiotensin-converting enzyme (ACE) inhibitors, ramipril and perindopril, may reduce the occurrence of major cardiovascular events in patients with proven atherosclerotic disease. The recently published results of the PRoFESS and TRANSCEND trials completed the much needed information concerning the use of an angiotensin receptor blocker for patients at high risk of cardiovascular events. PROFESS compared a therapy of telmisartan 80 mg daily with placebo in patients with a recent ischemic stroke. The difference in the primary outcome of first recurrent stroke was not statistically significant between telmisartan and placebo. The secondary outcome of major cardiovascular events showed a relative risk reduction (RRR) of 7% in favour of telmisartan. This tended to be significant (p = 0.06) despite a rather short follow-up period of only 28 months. In TRANSCEND 5926 patients at high risk for cardiovascular events were randomized to a treatment with telmisartan 80 mg daily or placebo for a mean duration of follow-up of 56 months. The primary composite outcome of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure showed a non-significant 8% RRR in favour of the telmisartan treated patients. The main secondary outcome of cardiovascular death and myocardial infarction or stroke as used in the HOPE trial showed a non-significant RRR of 13% in favour of telmisartan treated patients (p = 0.068 adjusted for multiplicity of comparisons). In comparing the Kaplan-Meier curves for the endpoint of major cardiovascular events used in HOPE, EUROPA, TRANSCEND and PRoFESS, the trends are similar. Results of most of the recently published trials have been neutral.This could partly be explained by major improvements in the optimal background therapy of the patients included. Nevertheless, the results of PRoFESS and TRANSCEND do not contradict the results from previous studies with

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

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    V. Srinivasan

    2016-11-01

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

  4. Prescription of renin–angiotensin system blockers and risk of acute kidney injury: a population-based cohort study

    Science.gov (United States)

    Nitsch, Dorothea; Smeeth, Liam; Bhaskaran, Krishnan; Tomlinson, Laurie A

    2016-01-01

    Objective To investigate whether there is an association between use of ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) and risk of acute kidney injury (AKI). Study design We conducted a new-user cohort study of the rate of AKI among users of common antihypertensives. Setting UK primary care practices contributing to the Clinical Practice Research Datalink (CPRD) eligible for linkage to hospital records data from the Hospital Episode Statistics (HES) database between April 1997 and March 2014. Participants New users of antihypertensives: ACEI/ARB, β-blockers, calcium channel blockers and thiazide diuretics. Outcomes The outcome was first episode of AKI. We estimated incidence rate ratio (RR) for AKI during time exposed to ACEI/ARB compared to time unexposed, adjusting for age, sex, comorbidities, use of other antihypertensive drugs and calendar period using Poisson regression. Covariates were time updated. Results Among 570 445 participants, 303 761 were prescribed ACEI/ARB with a mean follow-up of 4.1 years. The adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 1.12 (95% CI 1.07 to 1.17). This relative risk varied depending on absolute risk of AKI, with lower or no increased relative risk from the drugs among those at greatest absolute risk. For example, among people with stage 4 chronic kidney disease (who had 6.69 (95% CI 5.57 to 8.03) times higher rate of AKI compared to those without chronic kidney disease), the adjusted RR of AKI during time exposed to ACEI/ARB compared to time unexposed was 0.66 (95% CI 0.44 to 0.97) in contrast to 1.17 (95% CI 1.09 to 1.25) among people without chronic kidney disease. Conclusions Treatment with ACEI/ARB is associated with only a small increase in AKI risk while individual patient characteristics are much more strongly associated with the rate of AKI. The degree of increased risk varies between patient groups. PMID:28003286

  5. Effects of telmisartan vs olmesartan on metabolic parameters, insulin resistance and adipocytokines in hypertensive obese patients Efectos de telmisartan vs olmesartan sobre parámetros antropométricos, resistencia a la insulina y adipocitoquinas en pacientes hipertensos obesos

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    D. A. de Luis

    2010-04-01

    Full Text Available Background: Angiotensin II regulates the production of adipokines. The objective was to study the effect of treatment with telmisartan versus olmesartan in hypertensiveobese and overweight patients. Subjects: A sample of 65 overweight and obese patients with mild to moderate hypertension was analyzed in a prospective way with a randomized trial. Patients were randomized to telmisartan (80 mg/day or olmesartan (40 mg/day for 3 months. Weight, body mass index, blood pressure, basal glucose, insulin, total cholesterol, LDLcholesterol, HDL-cholesterol, triglycerides, HOMA, QUICKI, leptin and adiponectin were determined at basal time and after 3 months of treatment. Results: Sixty five patients gave informed consent and were enrolled in the study. Patients treated with telmisartan had a significative decrease of glucose 10.53 mg/dl (CI 95%: 2.6-18.5, insulin 2.51 mUI/L (CI 95%: 2.07-7.17 and HOMA 1.08 (CI 95%: 0.39-2.55. Patients treated with olmesartan had a significative decrease of total cholesterol 20.2 mg/dl (CI 95%: 5.8-34.9 and LDL cholesterol 22.6 mg/dl (CI 95%: 9.7-35.6. Only leptin levels have a significant decrease in telmisartan group 7.39 ng/ml (CI 95%: 1.47-13.31. Conclusion: Telmisartan improved blood pressure, glucose, insulin, HOMA and leptin in hypertensive diabetic patients. Olmesartan improved blood pressure and lipid levels.Introducción: La angiotensina II puede regular la producción de adipocitoquinas. El objetivo de nuestro trabajo fue evalaur el efecto sobre parámetros bioquímicos del tratamiento con telmisartan versus olmesartan en pacientes obesos hipertensos. Pacientes: Se analizó una muestra de 65 pacientes con hipertensión moderada severa y obesidad, mediante un ensayo clínico randomizado. Los pacientes fueron randomizados en dos ramas; telmisartan (80 mg/día u olmesartan (40 mg/día durante 3 meses. Se determinaron en el tiempo basal y tras 3 meses los siguientes parámetros; peso, índice de masa corporal, presi

  6. Mechanism and Effect of Telmisartan on Improving Insulin Resistance in OLETF Rats%替米沙坦对改善OLETF大鼠胰岛素抵抗作用的探讨

    Institute of Scientific and Technical Information of China (English)

    赵姜; 田凤石; 雒瑢

    2012-01-01

    目的:研究血管紧张素Ⅱ1型(AT1)受体阻滞剂替米沙坦对改善OLETF大鼠胰岛素抵抗(IR)的作用.方法:OLETF大鼠47只,高脂喂养14周诱导建立IR大鼠模型并将其随机分为5组:IR对照组(IR组)、二甲双胍(MET)组、吡格列酮(P)组、替米沙坦(L)组、低剂量替米沙坦(VL)组,12只LETO大鼠为正常对照(NC)组.干预26周后测定空腹胰岛素(FINS)、游离脂肪酸(FFA)、网膜素、视黄醇结合蛋白4(RBP4)、内脂素、空腹血糖(FBG)及血脂,计算胰岛素抵抗指数(IIOMA-IR)和胰岛素敏感性指数(ISI).结果:L组较IR组的血清网膜素、ISI升高(P<0.05或P<0.01);RBP4、内脂素、FBG、HOMA-IR、TC、LDL-C和FFA降低(P<0.05或P<0.01).多元线性逐步回归分析显示网膜素、ISI是RBP4水平的影响因素;网膜素、HOMA-IR是内脂素水平的影响因素.结论:替米沙坦可能通过提高血清网膜素、降低血清RBP4和内脂素调节血脂水平,从析改善IR.%Objective:To investigate the mechanism and effect of angiotensin II type 1 (AT1) receptor blocker telmisartan in OLETF rats with insulin resistance (lR). Methods: Forty-seven male OLETF rats were fed with high-fat diet for 14 weeks to establish the insulin resistance model, and rats were randomly assigned into five groups, IR model group, metformin (MET) group, the pioglitazone (P) group, the telmisartan (L) group and low-dose telmisartan (VL) group. Twelve LETO rats fed with normal diet served as the normal control (NC) group. The serum levels of fasting insulin (FINS), free fatty acids (FFA), omentin, retinol binding protein 4 (RBP4), visfatin, plasma level of fasting blood glucose (FBG) and blood lipid were detected after 26 weeks treatment. The insulin resistance index (HOMA-IR) and insulin sensitivity index(Isl)were calculated. R9-sultS: Compared with group IR, the serum omentin and ISI were significantly higher in L group (P < 0.01 or P < 0.05), and the serum RBP4, visfatin, FBG, HOMA-IR, total

  7. The impact of telmisartan on angiotensin converting enzyme 2 mRNA expression in monocyte-derived macrophages of diabetic hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    李永勤

    2013-01-01

    Objective To investigate the effects of telmisartan on the expression of angiotensin converting enzyme 2(ACE2) mRNA in monocyte-derived macrophages of hypertensive patients accompanied with diabetes. Methods 62 essential hypertensive patients accompanied with

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

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    Priscyla Zenteno-Castillo

    2015-12-01

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

  9. Renoprotective effect of a combination of garlic and telmisartan against ischemia/reperfusion-induced kidney injury in obese rats.

    Science.gov (United States)

    Ali, Sousou Ibrahim; Alhusseini, Naglaa Fathy; Atteia, Hebatallah Husseini; Idris, Reham Abd El-Satar; Hasan, Rehab Abdallah

    2016-09-01

    Obesity enhances the frequency and severity of acute kidney injury (AKI). Telmisartan pre-treatment was used experimentally in the amelioration of ischemia/reperfusion (IR)-induced AKI. However, there is a lack of evidence regarding its beneficial effects on AKI in obese animals. The present study, therefore, aimed to explore the protective effects of garlic and/or telmisartan against renal damage induced by unilateral IR in obese rats. Meloxicam was used as a standard anti-inflammatory agent. Prophylactic oral administration of meloxicam (3 mg kg(-1)), garlic (500 mg kg(-1)) and/or telmisartan (5 and 10 mg kg(-1)) for 4 wk protected against renal function deterioration induced by IR in obese rats. Both doses of telmisartan significantly reduced serum total cholesterol and triacyglycerol levels as well as peri-renal adipocytes size and renal fibrosis. Renal nuclear factor-kappa B immunoreactivity, tumor necrosis factor-alpha content as well as interleukin-10, adiponectin receptor 1 and macrophages (M1, M2) polarization markers (CD11c, CD206) mRNA expressions were down-regulated in ischemic kidney tissues and white adipose tissues around them by all treatments. Moreover, garlic, telmisartan and their combinations significantly suppressed oxidative stress in renal ischemic tissues. Histological picture was also improved by these treatments. Interestingly, the combinations provided a greater protection than their monotherapy in a dose-dependent manner. We suppose that this combination may be a promising prophylactic regimen for managing AKI in case of obesity. Thus, future experimental and clinical large-scale studies are necessary.

  10. 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

  11. Calcium channel blockers and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yi Tan; Yulin Deng; Hong Qing

    2012-01-01

    Alzheimer's disease is characterized by two pathological hallmarks: amyloid plaques and neurofi-brillary tangles. In addition, calcium homeostasis is disrupted in the course of human aging. Recent research shows that dense plaques can cause functional alteration of calcium signals in mice with Alzheimer's disease. Calcium channel blockers are effective therapeutics for treating Alzheimer's disease. This review provides an overview of the current research of calcium channel blockers in-volved in Alzheimer's disease therapy.

  12. Pharmacogenetics of ophthalmic topical β-blockers

    OpenAIRE

    Sidjanin, Duska J.; McCarty, Catherine A.; Patchett, Richard; Smith, Edward; Wilke, Russell A.

    2008-01-01

    Glaucoma is the second leading cause of blindness worldwide. The primary glaucoma risk factor is elevated intraocular pressure. Topical β-blockers are affordable and widely used to lower intraocular pressure. Genetic variability has been postulated to contribute to interpersonal differences in efficacy and safety of topical β-blockers. This review summarizes clinically significant polymorphisms that have been identified in the β-adrenergic receptors (ADRB1, ADRB2 and ADRB3). The implications ...

  13. Evaluation and Comparison of Anticonvulsant Activity of Telmisartan and Olmesartan in Experimentally Induced Animal Models of Epilepsy

    Science.gov (United States)

    V H, Pushpa; R N, Suresha; M K, Jayanthi; V, Ashwini; P S, Vaibhavi

    2014-01-01

    Background: Epilepsy is one common neurological disorder requiring newer targets and newer drugs for its efficient management. In the recent days brain renin angiotensin system has gained immense importance because of its involvement in seizure regulation. Objective: To evaluate and compare antiepileptic activity of different doses olmesartan and telmisartan on MES and PTZ induced seizure models. Materials and Methods: Swiss albino mice weighing around 25-30g of either sex were divided into 6 groups: Control ( Distilled Water- 10ml/kg), Standard – Sodium valproate (40mg/kg), O1 – Olmesartan (2.5mg/kg), O2 – Olmesartan (5mg/kg), T1 - Telmisartan (5mg/kg), T2 – Telmisartan (10mg/kg). After 1hour of administration of control , test and standard drugs (orally), convulsions were induced by administering PTZ (70mg/kg – i.p.) in PTZ model. Seizure latency was the parameter recorded. In MES model, suppression of tonic hind limb extension was taken as measure of efficacy. Result: The results were analysed by one-way-ANOVA followed by Bonferroni’s multiple comparison test. In MES test, dose dependently olmesartan and telmisartan significantly reduced the duration of tonic hindlimb extension in comparison to control (p<0.05). T2 – 9 + 0.89secs significantly reduced the tonic hind limb extension compared to other test groups (p<0.05). The percentage inhibition of seizure was T2-44.3%, O2-28.2%, T1-17.5%, O1- 12.3% respectively. In PTZ test, dose dependently olmesartan and telmisartan produced significant increase in seizure latency (p<0.05). T2 - 206.6+9.83secs significantly increased seizure latency compared to other test groups (p<0.05). Percentage protection from seizure is T2-52.6%, O2- 45.13%, T1- 37.5%, O1- 38.4% respectively. Conclusion: AT1 receptor antagonist, telmisartan and olmesartan in a dose dependent manner showed increase in antiepileptic activity. Temisartan at higher dose produced significant antiepileptic activity in comparison to olmesartan

  14. Inhibition of tumor necrosis factor-alpha-induced interleukin-6 expression by telmisartan through cross-talk of peroxisome proliferator-activated receptor-gamma with nuclear factor kappaB and CCAAT/enhancer-binding protein-beta.

    Science.gov (United States)

    Tian, Qingping; Miyazaki, Ryohei; Ichiki, Toshihiro; Imayama, Ikuyo; Inanaga, Keita; Ohtsubo, Hideki; Yano, Kotaro; Takeda, Kotaro; Sunagawa, Kenji

    2009-05-01

    Telmisartan, an angiotensin II type 1 receptor antagonist, was reported to be a partial agonist of peroxisome proliferator-activated receptor-gamma. Although peroxisome proliferator-activated receptor-gamma activators have been shown to have an anti-inflammatory effect, such as inhibition of cytokine production, it has not been determined whether telmisartan has such effects. We examined whether telmisartan inhibits expression of interleukin-6 (IL-6), a proinflammatory cytokine, in vascular smooth muscle cells. Telmisartan, but not valsartan, attenuated IL-6 mRNA expression induced by tumor necrosis factor-alpha (TNF-alpha). Telmisartan decreased TNF-alpha-induced IL-6 mRNA and protein expression in a dose-dependent manner. Because suppression of IL-6 mRNA expression was prevented by pretreatment with GW9662, a specific peroxisome proliferator-activated receptor-gamma antagonist, peroxisome proliferator-activated receptor-gamma may be involved in the process. Telmisartan suppressed IL-6 gene promoter activity induced by TNF-alpha. Deletion analysis suggested that the DNA segment between -150 bp and -27 bp of the IL-6 gene promoter that contains nuclear factor kappaB and CCAAT/enhancer-binding protein-beta sites was responsible for telmisartan suppression. Telmisartan attenuated TNF-alpha-induced nuclear factor kappaB- and CCAAT/enhancer-binding protein-beta-dependent gene transcription and DNA binding. Telmisartan also attenuated serum IL-6 level in TNF-alpha-infused mice and IL-6 production from rat aorta stimulated with TNF-alpha ex vivo. These data suggest that telmisartan may attenuate inflammatory process induced by TNF-alpha in addition to the blockade of angiotensin II type 1 receptor. Because both TNF-alpha and angiotensin II play important roles in atherogenesis through enhancement of vascular inflammation, telmisartan may be beneficial for treatment of not only hypertension but also vascular inflammatory change.

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

    Directory of Open Access Journals (Sweden)

    Luis Miguel  Ruilope

    2007-03-01

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

  16. On the top of ARB N/L type Ca channel blocker leads to less elevation of aldosterone

    Science.gov (United States)

    Konoshita, Tadashi; Kaeriyama, Saori; Urabe, Machi; Nakaya, Takahiro; Yamada, Mika; Ichikawa, Mai; Yamamoto, Katsushi; Sato, Satsuki; Imagawa, Michiko; Fujii, Miki; Makino, Yasukazu; Zenimaru, Yasuo; Wakahara, Shigeyuki; Suzuki, Jinya; Ishizuka, Tamotsu; Nakamura, Hiroyuki

    2016-01-01

    The activation of the renin–angiotensin system (RAS) is one of the unfavourable characteristics of calcium channel blocker (CCB). N type calcium channel is thought to be involved in renin gene transcription and adrenal aldosterone release. Accordingly, N/L type CCB has a possibility of less elevation of plasma aldosterone concentrations (PAC) among CCBs. In a monotherapy study, we had already demonstrated that N/L type CCB leads to less activation of the RAS compared with L type CCB. The objective of this study is to substantiate the hypothesis that at the condition of additive administration on the top of an angiotensin receptor blocker (ARB), still N/L type CCB leads to less elevation of PAC compared with L type one. Subjects were 60 hypertensives administered with valsartan. As an open label study, amlodipine (L type) or cilnidipine (N/L type) were administered on the top of valsartan (ARB) in a cross-over manner. Results were as follows (valsartan+amlodipine compared with valsartan+cilnidipine): systolic blood pressure (SBP)/diastolic blood pressure (DBP) (mmHg): 132±10/76±10 compared with 131±10/77±9, P=0.95/0.48, plasma renin activity (PRA) (ng/ml·h): 2.41±2.67 compared with 2.00±1.50 P=0.20, PAC (pg/ml): 77.3±31.0 compared with 67.4±24.8, P<0.05, urinary albumin excretion (UAE) (mg/gCr): 105.9±216.1 compared with 73.9±122.2, P<0.05. Thus, PAC at cilnidipine was significantly lower than those at amlodipine in spite of the comparable BP reductions. Besides, UAE was significantly lower at cilnidipine. In conclusion, on the top of the ARB, it is suggested that cilnidipine administration might lead to less elevation of PAC and reduction in UAE compared with amlodipine. PMID:27515419

  17. Graphical Synthetic Routes of Telmisartan%替米沙坦合成路线图解

    Institute of Scientific and Technical Information of China (English)

    徐桂清; 李伟; 郝二军

    2009-01-01

    @@ 替米沙坦(telmisartan,1),化学名为4'-[[1,4'-二甲基-2'-丙基(2,6'-双-1H-苯并咪唑)-1'-基]-甲基][1,1'-联苯基]-2-羧酸,由德国BoehringerIngelheim药厂开发,1999年首次在美国上市,商品名为Micardis[1,2],2001年在我国进口上市.本品是一种非肽类血管紧张素Ⅱ受体转换酶拮抗剂,可选择性阻断血管紧张素Ⅱ与AT1受体结合,从而阻断血管紧张素Ⅱ的血管收缩和醛固酮分泌作用.

  18. Combination of telmisartan with sildenafil ameliorate progression of diabetic nephropathy in streptozotocin-induced diabetic model.

    Science.gov (United States)

    El-Mahdy, Nageh Ahmed; El-Sayad, Magda El-Sayed; El-Kadem, Aya Hassan

    2016-07-01

    Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the world. Several signaling pathways are involved in the pathogenesis of DN including elevation in level of angiotensin II, formation of advanced glycation end products (AGE), activation of protein kinase c (PKC), and lipid accumulation. These pathways activate one another mutually leading to oxidative stress, increasing expression of transforming growth factor beta-1(TGF-β 1) and release of interleukins and adhesion molecules, so the aim of this study is to interrupt more than pathogenic pathway to ameliorate the progression of DN. In the present study, white male rats (N=48) were divided into six groups (8 rats each), the first two groups served as normal control and a control vehicle group while the remaining four groups were rendered diabetic by a single intraperitoneal injection of Streptozotocin (STZ) and being left for 4 weeks to develop DN. Thereafter, the rats were divided into DN group, DN group receiving Telmisartan or Sildenafil or Telmisartan Sildenafil combination. After the specified treatment period, urine samples were collected (using metabolic cages) to measure proteinuria, animals were then euthanized, blood and tissue samples were collected for measurement of Blood glucose,BUN, S.Cr, LDL, NO, TGF-β1, IL-1β, AGEPs, and SOD. The combination therapy showed significant decrease in BUN, S.Cr,LDL, TGF-β1, IL-1β, Proteinuria and AGEPs and significant increase in SOD and NO. The findings showed that combination therapy was able to ameliorate DN and that the effects were superior to the single drugs alone.

  19. Detrimental effects of beta-blockers in COPD - A concern for nonselective beta-blockers

    NARCIS (Netherlands)

    van der Woude, HJ; Zaagsma, J; Postma, DS; Winter, TH; van Hulst, M; Aalbers, R

    2005-01-01

    Introduction: beta-Blockers are known to worsen FEV1 and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment. Design: A double-blind, placebo-controlled, randomized,

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

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    Koval Stephen

    2007-10-01

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

  1. Effect of telmisartan and enalapril on ventricular remodeling and kidney prognosis of patients with coronary artery disease complicated with diabetic nephropathy

    Science.gov (United States)

    Hou, Yuyan; Zhang, Fucheng; Liu, Zhiqiang; Su, Shuhong; Wu, Xiao; Wang, Zhifang

    2017-01-01

    The aim of the present study was to compare the value of telmisartan and enalapril on ventricular remodeling and kidney prognosis of patients with coronary artery disease complicated with diabetic nephropathy, and provide discussion on clinical reasonably chosen medicine. A total of 60 cases of coronary artery disease complicated with diabetic nephropathy were randomly divided for telmisartan (80 mg/day) treatment (n=32), enalapril (10 mg/day) treatment (n=28), while the rest of the therapy was kept the same. After 12 weeks, the clinical effects were compared between different groups. It was found that in comparison with enalapril group, the left ventricular ejection fraction of telmisartan group was significantly higher, and left ventricular end-diastolic diameter was significantly lower (P<0.05). The serum creatinine level and 24-h protein of telmisartan group were significantly lower than that for the enalapril group (P<0.05). In conclusion, the regular telmisartan treatment for patients with coronary artery disease complicated with diabetic nephropathy is better than enalapril on ventricular remodeling and kidney prognosis. PMID:28123481

  2. Development and Validation of Stability-Indicating HPTLC Method for Simultaneous Determination of Telmisartan and Cilnidipine in Combined Tablet Dosage Form

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    Santosh R. Butle

    2015-11-01

    Full Text Available A new simple, accurate, precise and selective stability-indicating high performance thin layer chromatographic (HPTLC method has been developed and validated for simultaneous estimation of Telmisartan and Cilnidipine in combined tablet dosage form. The mobile phase selected was Toluene: Methanol: Glacial acetic acid (8: 2: 1, v/v/v with UV detection at 260 nm. The retention factor for Telmisartan and Cilnidipine were found to be 0.38 ± 0.004 and 0.62 ± 0.007. The method was validated with respect to linearity, accuracy, precision and robustness. The drugs were subjected to stress condition of hydrolysis (acid, base, oxidation, photolysis and thermal degradation. Results found to be linear in the concentration range of 200-1400ng band-1 and 50-600ng band-1 for Telmisartan and Cilnidipine, respectively. The method has been successfully applied for the analysis of drugs in pharmaceutical formulation. The % assay (Mean ± S.D. was found to be 100.79 ± 1.38 for Telmisartan and 99.55 ± 1.13 for Cilnidipine. The developed and validated stability indicating method can be used for assessing the stability of Telmisartan and Cilnidipine in bulk drug and pharmaceutical dosage form.

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

    Directory of Open Access Journals (Sweden)

    C. Di Filippo

    2014-01-01

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

  4. Clinical efficacy and safety of telmisartan versus losartan and their effect on lipid profile in stage 1 hypertension: A randomized, double blind, 12 week trial

    Directory of Open Access Journals (Sweden)

    Anoop Madhukar Salve

    2015-04-01

    Full Text Available The aim of this study was to compare the efficacy and safety of telmisartan and losartan and also to examine their effect on lipid profile in patients of stage 1 hypertension.Method: Sixty three stage 1 hypertensive patients were divided randomly into telmisartan  and losartan  group of 32 and 31 patients respectively. At baseline and 12 weeks, systolic (SBP and diastolic blood pressure (DBP, blood sugar level (BSL, total cholesterol (TC, triglycerides (TG, low density lipoprotein (LDL, very low density lipoprotein (VLDL and high density lipoprotein (HDL were measured. Result: The primary finding of the present study was that telmisartan and losartan significantly decreased SBP and DBP at 12 weeks compared to baseline but there was no significant difference in reduction of blood pressure in between both groups. It was also observed that fasting blood sugar level, serum total cholesterol, triglyceride, VLDL, and LDL decreased significantly and HDL increased significantly (p <0.001 after 12 weeks of treatment in telmisartan group only. No serious adverse effects were reported during the study. Conclusion: It was observed that only telmisartan and not losartan significantly improved lipid profile at 12 weeks.

  5. 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

  6. Drug: D09743 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09743 Mixture, Drug Telmisartan - amlodipine besilate mixt; Micamlo (TN) Telmisartan...l organs 21 Cardiovascular agents 214 Antihypertensives 2149 Others D09743 Telmisartan...NS C09DB Angiotensin II antagonists and calcium channel blockers C09DB04 Telmisartan... and amlodipine D09743 Telmisartan - amlodipine besilate mixt PubChem: 124490483 ...

  7. Investigation and correlation of physical stability, dissolution behaviour and interaction parameter of amorphous solid dispersions of telmisartan: a drug development perspective.

    Science.gov (United States)

    Dukeck, R; Sieger, P; Karmwar, P

    2013-07-16

    The aim of this study was to investigate if amorphous solid dispersions of telmisartan, prepared in presence of different polymers, exhibit different structural and thermodynamic characteristics and whether these differences can be correlated to their physical stability (time to crystallisation) and dissolution behaviour. Amorphous samples were prepared by melt quenching. The resulting amorphous materials were characterised using X-ray diffraction, Raman spectroscopy and differential scanning calorimetry. All freshly prepared samples were completely X-ray amorphous (with a halo being the only feature in the diffractograms). The shape of the halos in the diffractograms varied suggesting structural variations in the near order of the molecules between the different amorphous solid dispersions (ASDs). Principal component analysis of the Raman spectra of the various ASD revealed that the samples clustered in the scores plot, again suggesting structural differences due to the presence of different drug-polymer interaction. The ranking of the samples with respect to physical stability and interaction parameter was: ASD of telmisartan:eudragit>ASD of telmisartan:soluplus>ASD of telmisartan:HPMC>ASD of telmisartan:PVP>amorphous telmisartan. The interaction parameter, calculated by using the Flory Huggins theory, showed a good correlation with the experimentally determined stability whereas a weak correlation was found with dissolution behaviour of different ASD. This study showed that correlation of physical stability and dissolution behaviour with calculated interaction parameter is possible for the same amorphous systems prepared by using different polymers. This could aid in selecting the most appropriate polymer for the development of optimised formulations containing amorphous drugs. It can be concluded that ASD prepared by using different polymers have different structural and thermal properties. These differences affect the physical stability and dissolution

  8. Amorphous ternary cyclodextrin nanocomposites of telmisartan for oral drug delivery: improved solubility and reduced pharmacokinetic variability.

    Science.gov (United States)

    Sangwai, Mayur; Vavia, Pradeep

    2013-09-10

    Despite of advancements in dosage form design and use of multifunctional excipients, improvement in dissolution characteristics of molecules like Telmisartan (TEL) having exceedingly pH dependent and poor solubility profile is still challenging. The present research work explores an innovative particle engineering approach which synergistically coalesce two principally different solubility enhancement strategies namely ternary β-cyclodextrin complexation and top-down nanonization in a unit process. The research was aimed to improve solubility and reduce in vivo variability in pharmacokinetic parameters of TEL irrespective to physiological pH conditions. Ternary β-cyclodextrin nanocomposites of TEL were prepared with high pressure homogenization using meglumine as ternary component. TEL nanocomposites were thoroughly characterized for particle size, surface topology, surface charge, inclusion complexation, crystalinity, dissolution and in vivo pharmacokinetic performance in male wistar rats at fed and fasted state. TEL nanocomposites exhibited average particle size of 698 ± 23 nm. Remarkable improvement in in vitro dissolution characteristics in multimedia and biorelevant media was observed in comparison with plain drug and marketed formulation. Results of in vivo pharmacokinetic studies revealed that, nanocomposites effectively bypass variation in pharmacokinetic parameters at fed and fasted states with 346%, 315%, 301% and 321% increase in relative bioavailability compared to marketed formulation and pure TEL in fed and fasted conditions respectively.

  9. In-Vitro Characterization and Oral Bioavailability of Organic Solvent-free Solid Dispersions Containing Telmisartan

    Science.gov (United States)

    Cao, Yue; Shi, Li-Li; Cao, Qing-Ri; Yang, Mingshi; Cui, Jing-Hao

    2016-01-01

    Poorly water-soluble drugs often suffer from limited or irreproducible clinical response due to their low solubility and dissolution rate. In this study, organic solvent-free solid dispersions (OSF-SDs) containing telmisartan (TEL) were prepared using polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 6000 (PEG 6000) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant by a lyophilization method. In-vitro dissolution rate and physicochemical properties of the OSF-SDs were characterized using the USP I basket method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and fourier transform-infrared (FT-IR) spectroscopy. In addition, the oral bioavailability of OSF-SDs in rats was evaluated by using TEL bulk powder as a reference. The dissolution rates of the OSF-SDs were significantly enhanced as compared to TEL bulk powder. The results from DSC, XRD showed that TEL was molecularly dispersed in the OSF-SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between TEL and its carriers. The OSF-SDs exhibited significantly higher AUC0–24 h and Cmax, but similar Tmax as compared to the reference. This study demonstrated that OSF-SDs can be a promising method to enhance the dissolution rate and oral bioavailability of TEL. PMID:27642309

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

    Directory of Open Access Journals (Sweden)

    Panikumar Durga Anumolu

    2014-04-01

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

  11. Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan.

    Science.gov (United States)

    Zhang, Yanzhuo; Zhi, Zhuangzhi; Jiang, Tongying; Zhang, Jinghai; Wang, Zhanyou; Wang, Siling

    2010-08-03

    The purpose of this study was to develop mesoporous silica nanoparticles (MSNs) loaded with a poorly water-soluble drug, intended to be orally administered, able to improve the dissolution rate and enhance the drug loading capacity. Spherical MSNs were synthesized using an organic template method in an oil/water phase, and large pore diameter MSNs were functionalized with aminopropyl groups through postsynthesis. MSNs as well as the resulting functionalized MSNs were investigated as matrices for loading and release of the model drug telmisartan (TEL). The effects of different pore sizes and surface chemical groups on TEL uptake and release were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC. The total pore volume and the pore diameter of MSNs were the two main factors limiting the maximum drug load capacity. MSNs allow a very high drug loading of about 60% in weight. The release rate of TEL from MSNs with a pore diameter of 12.9 nm was found to be effectively increased and the release rate of TEL from the functionalized MSNs was effectively controlled compared with that from the unmodified MSNs. We believe that the present study will help in the design of oral drug delivery systems for the dissolution enhancement and/or sustained release of poorly water-soluble drugs.

  12. DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR SIMULTANEOUS ESTIMATION OF METOPROLOL SUCCINATE AND TELMISARTAN IN COMBINED PHARMACEUTICAL FORMULATION

    Directory of Open Access Journals (Sweden)

    Mayur Modi*, Rikin Shah and R.C. Mashru

    2012-05-01

    Full Text Available Four simple, rapid, precise, economical and accurate spectrophotometric methods have been developed for simultaneous analysis of Metoprolol succinate and Telmisartan in their combined dosage form. Method 1, First derivative simultaneous equation method (Vierodt’s method. It employs formation and solving of simultaneous equation using two wavelengths 230.2 nm (λmax of Metoprolol succinate and 237 nm (λmax of Telmisartan in first derivative spectra. Method 2, First derivative Q-Absorbance equation method. It involves, formation of Q-absorbance equation at 231.8 nm (isoabsorptive point and 237 nm (λmax of Telmisartan in first derivative spectra. Method 3, Absorbance correction method, involves measurement of absorbance at 296.6 nm for estimation of TEL and measurement of corrected absorbance at 223 nm for estimation of MET. Method 4, Combination of First derivative dual wavelength ,which uses the difference in absorbance at 282.4 nm and 284.6 nm for estimation of MET and zero crossing first derivative spectrophotometry involves measurement of amplitudes at 330 nm for estimation of TEL in first derivative spectra. Developed methods were validated according to ICH guidelines. The calibration graph follows Beer’s law in the range of 3-20 µg/ml for MET and 4-16 µg/ml for TEL with R square value greater than 0.999. Accuracy of all methods was determined by recovery studies and showed % recovery between 99 to 101%. Intraday and interday precision was checked for all methods and mean %RSD was found to be less than 2 for all the methods. The methods were successfully applied for estimation of MET and TEL in marketed formulation.

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

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    Muralikrishna Gangadharan Komala

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

  14. Lessons from ONTARGET.

    Science.gov (United States)

    Berlaimont, V; Billiouw, J-M; Brohet, C; Dupont, A G; Gazagnes, M-D; Heller, F; Krzesinski, J M; Missault, L; Persu, A; Piérard, L; Rottiers, R; Vanhooren, G; Van Mieghem, W; Vervaet, P; Herman, A G

    2008-01-01

    The recently published results of the ONTARGET trial shed a new light on the cardiovascular protection of patients at high risk of a cardiovascular event. Despite a number of trials looking at the efficacy of Angiotensin Converting Enzyme inhibitors (ACEis) or Angiotensin Receptor Blockers (ARBs) in the prevention of cardiovascular events in patients with specific high risk profiles, the question of the equivalence of ACEis and ARBs remained unanswered. The ONTARGET trial has shown that telmisartan 80 mg administered for a median duration of 4.5 years to patients at high risk of developing a major cardiovascular event, is equally effective to ramipril 10 mg. In addition, telmisartan was slightly better tolerated. The comparator ramipril has been chosen as it is currently the gold standard ACEi since the results of the HOPE study, in terms of the composite outcome of cardiovascular death, myocardial infarction and stroke. Moreover, ONTARGET is the first trial to test the hypothesis of superiority of adding an ARB (telmisartan 80 mg) to an ACEi (ramipril 10 mg) over the ACEi ramipril monotherapy in cardiovascular protection of the same broad range of high-risk patients. Surprisingly, despite a more pronounced blood pressure lowering, the combination of the two agents did not lead to an additional decrease in the number of events, but had significantly more side-effects compared to ramipril monotherapy. ONTARGET is a landmark study, performed according to the highest statistical and clinical standards, providing compelling evidence and clear answers to two important clinical questions.

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

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    Dhanya N

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  18. 浅析活性维生素D联合血管紧张素受体拮抗剂治疗IGA肾病有效性%Analysis of the Effectiveness of Active Vitamin D Combined With Angiotensin Receptor Antagonist in the Treatment of IGA Nephropathy

    Institute of Scientific and Technical Information of China (English)

    郭陆晋

    2015-01-01

    目的:分析活性维生素D联合血管紧张素受体拮抗剂治疗IGA肾病有效性。方法随机抽取2010年4月~2014年11月诊治的80例IgA肾病患者,分为研究组和对比组。对比组服用厄贝沙坦进行治疗。而研究组在对比组的基础上增加骨化三醇胶丸进行治疗,分析两组治疗效果。结果在治疗结束之后,两组患者的尿蛋白的数值低于治疗(P 0.05)。结论活性维生素D联合血管紧张素受体拮抗剂治疗IGA肾病效果显著,其安全性高。%Objective To analyze the effectiveness of active vitamin D combined with angiotensin receptor antagonist in the treatment of IGA nephropathy. Methods 80 patients with IgA nephropathy in April 2010~November 2014 were randomly divided into study group and control group. Contrast group took irbesartan treatment. The research group on the basis of the comparison group increased Calcitriol Soft Capsules treatment, analysis of the treatment effect of the two groups.ResultsAfter the treatment, the urine protein of the two groups was significantly lower than that of the treatment (P 0.05). Conclusion Active vitamin D combined with angiotensin receptor antagonist in the treatment of IGA nephropathy is remarkable, and its safety is high, it is worthy of clinical application.

  19. Renoprotective Effect of the Combination of Renin-angiotensin System Inhibitor and Calcium Channel Blocker in Patients with Hypertension and Chronic Kidney Disease

    Institute of Scientific and Technical Information of China (English)

    Rong-Shuang Huang; Yi-Ming Cheng; Xiao-Xi Zeng; Sehee Kim; Ping Fu

    2016-01-01

    Background:Renin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD).We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e.,ACEI/ARB + CCB) with ACEI/ ARB monotherapy in patients with hypertension and CKD.Methods:Publications were identified from PubMed,Embase,Medline,and Cochrane databases.Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered.The outcomes of end-stage renal disease (ESRD),cardiovascular events,BP,urinary protein measures,estimated glomerular filtration rate (GFR),and adverse events were extracted.Results:Based on seven RCTs with 628 patients,ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [RR] =0.84;95% confidence interval [CI]:0.52-1.33) and cardiovascular events (RR =0.58;95% CI:0.21-1.63) significantly,compared with ACEI/ARB monotherapy.There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] =-1.28 mmHg;95% CI:-3.18 to-0.62),proteinuria (standard mean difference =-0.55;95% CI:-1.41 to-0.30),GFR (WMD =-0.32 ml/min;95% CI:-1.53 to-0.89),and occurrence of adverse events (RR =1.05;95% CI:0.72-1.53).However,ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD =-4.46 mmHg;95% CI:-6.95 to-1.97),compared with ACEI/ARB monotherapy.Conclusion:ACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.

  20. Regulation of angiotensin-(1-7) and angiotensin Ⅱ type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure

    Institute of Scientific and Technical Information of China (English)

    Wen-na ZONG; Xin-zheng LU; Xiao-hui YANG; Xiu-mei CHEN; Hong-juan HUANG; Hong-jian ZHENG; Xiao-yi QIN; Yong-hong YONG; Ke-jiang CAO; Jun HUANG

    2011-01-01

    Aim:To investigate the possible effects of telmisartan and losartan on cardiac function in adriamycin (ADR)-induced heart failure in rats,and to explore the changes in plasma level of angiotensin-(1-7)[Ang-(1-7)] and myocardial expression of angiotensin Ⅱ type 1/2 receptors (AT1R / AT2R) and Mas receptor caused by the two drugs.Methods:Male Sprague-Dawley rats were randomly divided into 4 groups:the control group,ADR-treated heart failure group (ADR-HF),telmisartan plus ADR-treated group (Tel+ADR) and losartan plus ADR-treated group (Los+ADR).ADR was administrated (2.5 mg/kg,ip,6 times in 2 weeks).The rats in the Tel+ADR and Los+ADR groups were treated orally with telmisartan (10 mg/kg daily po) and losartan (30 mg/kg daily),respectively,for 6 weeks.The plasma level of Ang-(1-7) was determined using ELISA.The mRNA and protein expression of myocardial Mas receptor,AT1R and AT2R were measured using RT-PCR and Western blotting,respectively.Results:ADR significantly reduced the plasma level of Ang-(1-7) and the expression of myocardial Mas receptor and myocardial AT2R,while significantly increased the expression of myocardial AT1R.Treatment with telmisartan and losartan effectively increased the plasma level of Ang-(1-7) and suppressed myocardial AT1R expression,but did not influence the expression of Mas receptor and AT2R.Conclusion:The protective effects of telmisartan and losartan in ADR-induced heart failure may be partially due to regulation of circulating Ang-(1-7) and myocardial AT1R expression.

  1. Telmisartan provides protection against development of impaired vasodilation independently of metabolic effects in SHRSP.Z-Lepr(fa)/IzmDmcr rats with metabolic syndrome.

    Science.gov (United States)

    Kagota, Satomi; Tada, Yukari; Nejime, Namie; Nakamura, Kazuki; Kunitomo, Masaru; Shinozuka, Kazumasa

    2011-05-01

    Metabolic syndrome is known to facilitate the development of cardiovascular disease. We have demonstrated that mesenteric arteries of SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP-fatty) rats with metabolic syndrome display an impaired vasorelaxation response mediated by nitric oxide. We examined whether the condition could be alleviated by treatment with telmisartan, an angiotensin II type 1 (AT1) receptor antagonist with PPAR-γ-activating properties and compared the results with those from pioglitazone, a PPAR-γ agonist. Telmisartan (5 mg·kg(-1)·day(-1)) or pioglitazone (2.5 mg·kg(-1)·day(-1)) was orally administered to male SHRSP-fatty rats for 8 weeks. Serum triglyceride and cholesterol levels were determined, and the oral glucose tolerance test was performed to evaluate insulin resistance. Vasodilations in response to acetylcholine and nitroprusside were determined by wire myographs under isometric tension conditions, protein expressions of soluble guanylyl cyclase in mesenteric arteries by Western blotting, and the contents of 3-nitrotyrosine in aortas by high-performance liquid chromatography with electrochemical detection. Telmisartan exerted antihypertensive effects, while pioglitazone ameliorated metabolic abnormalities in SHRSP-fatty rats. Telmisartan increased acetylcholine- and nitroprusside-induced relaxation and soluble guanylyl cyclase protein expression in mesenteric arteries and reduced 3-nitrotyrosine content in aortas. Pioglitazone displayed no such alleviating effects on vascular functions. These findings indicate that telmisartan protects against vasodilation disturbance through anti-oxidative and -nitrative stress independently of metabolic effects in SHRSP-fatty rats with metabolic syndrome.

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

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    Yan HUANG

    2016-10-01

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

  3. Development of a validated liquid chromatographic method for determination of related substances of telmisartan in bulk drugs and formulations.

    Science.gov (United States)

    Rao, R Nageswara; Guru Prasad, K; Gangu Naidu, Ch; Maurya, Pawan K

    2011-11-01

    A simple and rapid reversed phase liquid chromatographic method for separation and determination of the related substances of telmisartan (TLM) was developed and validated. The chromatographic separation was achieved on Lichrospher RP-18 column (250 × 4.6 mm, 5 μm), using 20 mM ammonium acetate containing 0.1% (v/v) triethylamine (pH adjusted to 3.0 with trifluoroacetic acid) and acetonitrile as mobile phase at 25°C. The detection was performed at 254 nm. The method was validated and found to be robust, precise, specific and linear between 0.37 and 500 μg/mL. The limits of detection and quantification of telmisartan were 0.11 and 0.37 μg/mL, respectively. The method was successfully applied to quantify related substances and assay of TLM in bulk drugs and commercial tablets. The related substances relate to a novel synthetic route and different from those A-H impurities reported by European Pharmacopeia.

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    Marina Brito Silva

    2009-04-01

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

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

    OpenAIRE

    Marina Brito Silva; ALMEIDA, Angélica O.; Leandro Fadel; Ambrósio,Carlos E.; Maria Angélica Miglino

    2009-01-01

    A distrofia muscular de Duchenne (DMD) é uma alteração neuromuscular caracterizada por contínua necrose muscular e degeneração, com eventual fibrose e infiltração por tecido adiposo. O aumento progressivo da fibrose intersticial no músculo impede a migração das células miogênicas, necessárias para a formação muscular. O modelo canino constitui-se nas melhores fenocópias da doença em humanos, quando comparados com outros modelos animais com distrofia. O tratamento antifibrose de pacientes DMD,...

  7. Antitumoral, antihypertensive, antimicrobial, and antioxidant effects of an octanuclear copper(II)-telmisartan complex with an hydrophobic nanometer hole.

    Science.gov (United States)

    Islas, María S; Martínez Medina, Juan J; López Tévez, Libertad L; Rojo, Teófilo; Lezama, Luis; Griera Merino, Mercedes; Calleros, Laura; Cortes, María A; Rodriguez Puyol, Manuel; Echeverría, Gustavo A; Piro, Oscar E; Ferrer, Evelina G; Williams, Patricia A M

    2014-06-02

    A new Cu(II) complex with the antihypertensive drug telmisartan, [Cu8Tlm16]·24H2O (CuTlm), was synthesized and characterized by elemental analysis and electronic, FTIR, Raman and electron paramagnetic resonance spectroscopy. The crystal structure (at 120 K) was solved by X-ray diffraction methods. The octanuclear complex is a hydrate of but otherwise isostructural to the previously reported [Cu8Tlm16] complex. [Cu8Tlm16]·24H2O crystallizes in the tetragonal P4/ncc space group with a = b = 47.335(1), c = 30.894(3) Å, Z = 4 molecules per unit cell giving a macrocyclic ring with a double helical structure. The Cu(II) ions are in a distorted bipyramidal environment with a somewhat twisted square basis, cis-coordinated at their core N2O2 basis to two carboxylate oxygen and two terminal benzimidazole nitrogen atoms. Cu8Tlm16 has a toroidal-like shape with a hydrophobic nanometer hole, and their crystal packing defines nanochannels that extend along the crystal c-axis. Several biological activities of the complex and the parent ligand were examined in vitro. The antioxidant measurements indicate that the complex behaves as a superoxide dismutase mimic with improved superoxide scavenger power as compared with native sartan. The capacity of telmisartan and its copper complex to expand human mesangial cells (previously contracted by angiotensin II treatment) is similar to each other. The antihypertensive effect of the compounds is attributed to the strongest binding affinity to angiotensin II type 1 receptor and not to the antioxidant effects. The cytotoxic activity of the complex and that of its components was determined against lung cancer cell line A549 and three prostate cancer cell lines (LNCaP, PC-3, and DU 145). The complex displays some inhibitory effect on the A549 line and a high viability decrease on the LNCaP (androgen-sensitive) line. From flow cytometric analysis, an apoptotic mechanism was established for the latter cell line. Telmisartan and CuTlm show

  8. 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....

  9. Calcium channel blockers in cardiovascular pharmacotherapy.

    Science.gov (United States)

    Godfraind, Theophile

    2014-11-01

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

  10. 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

  11. Use of beta blockers in various clinical states

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    Radović Vesna V.

    2011-01-01

    Full Text Available 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 myocardial infarction in various clinical states and to eliminate doubts concerning their prescription. Beta blockers 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 follow-up 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. Discussion and conclusion. 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.

  12. DMPD: Lipopolysaccharide-binding molecules: transporters, blockers and sensors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15241548 Lipopolysaccharide-binding molecules: transporters, blockers and sensors. ...binding molecules: transporters, blockers and sensors. PubmedID 15241548 Title Lipopolysaccharide-binding mo...lecules: transporters, blockers and sensors. Authors Chaby R. Publication Cell Mo

  13. β-blockers as endocrine disruptors: the potential effects of human β-blockers on aquatic organisms.

    Science.gov (United States)

    Massarsky, Andrey; Trudeau, Vance L; Moon, Thomas W

    2011-06-01

    β-Adrenergic blockers or β-blockers have been used therapeutically to treat human hypertension since the late 1960s. The global market value and prescription rates of β-blockers keep rising substantially each year, and over the past decade the number of prescriptions has doubled. The widespread use of β-blockers has resulted in their appearance in the aquatic environment originating primarily from sewage effluents. The objective of this review is to analyze the literature as a means to determine the endocrine-disrupting potential of β-blockers in aquatic organisms. The mammalian adrenergic system is compared with the adrenergic system of fish and the homologous octopaminergic system in aquatic invertebrates, in particular mollusks. The structure and functions of these systems are linked to the molecular similarities between adrenoceptors and the octopaminergic/tyraminergic receptors, the various catecholamine molecules (epinephrine, norepinephrine, octopamine, and tyramine), and the processes controlled. Knowledge of these similarities as well as the effects of β-blockers, mainly in humans, is then used to create a broad picture of the endocrine-disrupting potential of β-blockers, particularly during the stress response. The main conclusion is that β-blockers have endocrine-disrupting effects.

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

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    Guo Zhixin

    2012-08-01

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

  15. The Cardio-renal Syndrome (CRS

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    Enrico V. Scabbia

    2015-12-01

    Therapeutic strategies involved in CRS treatment include the use of diuretics, ACE inhibitors, Angiotensin Receptor Blockers and β-Blockers, emphasizing the role of a proper use of medication indicated for the treatment of cardiac decompensation.

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

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    Kabeer Ahmed Shaikh

    2014-01-01

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

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

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    Colomba Falcone

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  19. Anxiolytics not acting at the benzodiazepine receptor: beta blockers.

    Science.gov (United States)

    Tyrer, P

    1992-01-01

    1. Although there is clear evidence for many controlled trials in the past 25 years that beta blockers are effective in anxiety disorders clear indications for their use are lacking. 2. The balance of evidence suggests that the mechanism of action of beta-blocking drugs is through peripheral blockade of beta-mediated symptoms. 3. Most evidence to the efficacy of beta-blockers comes from study of their use in generalized anxiety and in acute stress. 4. Because beta-blockers carry no risks of pharmacological dependence they may be preferred to many other anti-anxiety drugs.

  20. Effect of angiotensin-converting enzyme inhibitors and receptor blockers on appropriate implantable cardiac defibrillator shock in patients with severe systolic heart failure (from the GRADE Multicenter Study).

    Science.gov (United States)

    AlJaroudi, Wael A; Refaat, Marwan M; Habib, Robert H; Al-Shaar, Laila; Singh, Madhurmeet; Gutmann, Rebecca; Bloom, Heather L; Dudley, Samuel C; Ellinor, Patrick T; Saba, Samir F; Shalaby, Alaa A; Weiss, Raul; McNamara, Dennis M; Halder, Indrani; London, Barry

    2015-04-01

    Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensity-matched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m(2), those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73 m(2) and with neutral effect in those with GFR <30 ml/min/1.73 m(2).

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

    Directory of Open Access Journals (Sweden)

    Bülent Albayrak

    2016-01-01

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

  2. Renal vascular effects of calcium channel blockers in hypertension.

    Science.gov (United States)

    Benstein, J A; Dworkin, L D

    1990-12-01

    Recent evidence suggests that calcium channel blockers have specific effects on renal hemodynamics in patients with hypertension and may also slow the progression of chronic renal failure. When these agents are studied in vitro, their predominant effect is to reverse afferent arteriolar vasoconstriction induced by catecholamines or angiotensin II. Because efferent resistance may remain high, glomerular filtration rate rises while renal blood flow remains low. The effects in vivo are less consistent. In human hypertension, calcium channel blockers lower renal resistance and may raise both renal blood flow and glomerular filtration rate. In experimental models of chronic renal disease, calcium channel blockers slow the progression of renal damage; however, variable effects on renal hemodynamics have been found. Other factors implicated in the progression of renal damage, including compensatory renal hypertrophy, platelet aggregation, and calcium deposition, may also be favorably influenced by these agents. Recent studies suggest that calcium channel blockers may have similar protective effects in patients with hypertension and chronic renal disease.

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

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Vestergaard, Peter; Kassem, Moustapha

    2004-01-01

    beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density...... (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...

  4. 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...... trials (9 trials on propranolol, 1 case-control study and 4 retrospective analyses) were identified. One trial suggested an increased mortality in patients treated with beta-blockers and refractory ascites. The results of the remaining trials were inconclusive. No increase in mortality among beta-blocker......-treated patients was found in the present retrospective analysis. CONCLUSIONS: Treatment with beta-blockers may increase mortality in patients with cirrhosis and refractory ascites. However, the current evidence is sparse and high-quality studies are warranted to clarify the matter....

  5. [Takotsubo cardiomyopathy: a novel beta-adrenergic blocker withdrawal syndrome].

    Science.gov (United States)

    Tomcsányi, János; Jávor, Kinga; Arabadzisz, Hrisula; Zsoldos, András; Wagner, Vince; Sármán, Balázs

    2013-02-17

    The authors describe two cases of takotsubo cardiomyopathy developing after an abrupt withdrawal of carvedilol and bisoprolol. Takotsubo or stress cardiomyopathy is characterized by acute and reversible cardiac dysfunction without coronary artery disease. It is triggered by acute emotional or physical stress, drugs or drug withdrawal. The immediate discontinuation of the long acting vasodilator beta-blocker, carvedilol has not yet been described to cause takotsubo cardiomyopathy. The authors recommend cautious withdrawal of beta-blockers.

  6. 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....

  7. Pharmacogenetics of ophthalmic topical β-blockers\\ud

    OpenAIRE

    Sidjanin, Duska J.; McCarty, Catherine A.; Patchett, Richard; Smith, Edward M.; Wilke, Russell A.

    2008-01-01

    Glaucoma is the second leading cause of blindness worldwide. The primary glaucoma risk factor is elevated intraocular pressure. Topical β-blockers are affordable and widely used to lower intraocular pressure. Genetic variability has been postulated to contribute to interpersonal differences in efficacy and safety of topical β-blockers. This review summarizes clinically significant polymorphisms that have been identified in the β-adrenergic receptors (ADRB1, ADRB2 and ADRB3). The implications ...

  8. Non-selective beta-blockers decrease thrombotic events in patients with heart failure

    NARCIS (Netherlands)

    De Peuter, Olav R.; Souverein, Patrick C.; Klungel, Olaf H.; Lip, Gregory Y.; Buller, Harry R.; De Boer, Anthonius; Kamphuisen, Pieter W.

    2010-01-01

    Background: Beta-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of beta-blockers. The 2002 COMET study showed superiority of carvedilol (a non-selective beta-blocker) over metoprolol (selective beta-blocker) on mortality and cardiovascular events

  9. Rational application of antihypertensive calcium channel blockers in renal diseases%钙离子拮抗剂类降压药在肾脏病中的合理应用

    Institute of Scientific and Technical Information of China (English)

    王伟铭; 徐丽梨

    2014-01-01

    中国人群高血压发病率较高,其中继发性高血压第一位的病因就是慢性肾脏病(CKD)。对于CKD高血压患者首选血管紧张素转换酶抑制剂(ACEI)或血管紧张素II 受体拮抗剂(ARB)类药物,而单药治疗往往血压控制不佳,需联合其它降压药物治疗。钙离子拮抗剂(CCB)是一线降压药物,既往考虑其对肾脏副作用而较少应用于CKD患者。随着研究进展及新型制剂的研发, CCB类药物在CKD高血压治疗中亦有一定地位及优势,合理的应用可改善肾脏病预后,给患者带来益处。%The incidence of hypertension is high in the Chinese population.And the first cause of secondary hypertension is chronic kidney disease (CKD).To control the hypertension in CKD patients, angiotensin converting enzyme inhibitor (ACEI)or angiotensin receptor blocker (ARB)is the first choice. However,as single drug use of ACEI or ARB does not have satisfactory effect in controlling the hypertension of CKD patients,combination of other antihypertensive drugs is usually needed.Calcium channel blockers (CCB)are first-line antihypertensive drugs,but were less used in CKD patients previously due to their adverse effects.With the research progress and the development of new preparations,CCB have their certain places and advantages in treatment of hypertension patients with CKD.Rational application of CCB can improve prognosis of the kidney so as to benefit the patients.

  10. 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

  11. Advance of research on application of renin-angiotensin-aldosterone system blockers in elderly patients with chronic kidney disease%RAAS阻滞剂在老年慢性肾脏病中应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    张琪; 倪兆慧

    2014-01-01

    全球老龄人(年龄≥65岁)所占的人口比例正逐步上升。老年人由于其特殊的生理状态更易被一些慢性病如,高血压、糖尿病、慢性肾脏病( CKD)所困扰。肾素-血管紧张素-醛固酮系统( RAAS)的过分活跃可导致高血压、心血管事件及CKD的发生。因此,针对RAAS的治疗具有可行性。但老年患者在使用RAAS阻滞剂[主要包括血管紧张素转换酶抑制剂( ACEI)、血管紧张素受体阻滞剂( ARB)、肾素抑制剂、醛固酮拮抗剂]类药物时更易出现肾小球滤过率( GFR)下降、高钾血症、低血压等不良反应,所以临床使用时,需要特别平衡使用该类药物的利弊。尽管目前对老年人使用RAAS阻滞剂药物有限的研究大多获得了肯定的结论,但是,仍需要更多、更长周期的研究结果来探寻老年CKD患者使用RAAS阻滞剂的疗效和安全性,以及是否确实能减缓CKD的进展。%Theproportionofglobalolderpeople(age≥65years)isgraduallyincreasing.Because of their special physiological state,older people are more easily troubled by some chronic diseases such as hypertension,diabetes,and chronic kidney disease( CKD). Overactivity of renin-angiotensin-aldosterone system( RAAS)can lead to hypertension,cardiovascular events,as well as CKD. Therefore,the treatment targeting RAAS is feasible. However,while using RAAS blockers including angiotensin converting enzyme inhibitors( ACEI),angiotensin receptor blockers( ARB),renin inhibitors,and aldosterone antagonists, elderly patients are more likely to be subjected to decrease of glomerular filtration rate ( GFR ), hyperkalemia,and hypotension,etc,indicating that it is specially required to weigh the pros and cons before clinical use of such drugs. Although most limited researches on efficacy of RAAS blocker drugs in elderly patients obtained positive conclusions,more long-term studies are still needed to explore the therapeutic efficacy

  12. Effects of telmisartan in combined with L-carnitine on the oxidative stress and micro-inflammation status in peritoneal dialysis patients

    Institute of Scientific and Technical Information of China (English)

    Jin-Xiu Cheng; Xing Pan; Cui-Lan Liu; Hua Liu; Sheng-Jun Liu; Ling-Ling Wang

    2016-01-01

    Objective:To explore the effects of telmisartan in combined with L-carnitine on the oxidative stress and micro-inflammation status in peritoneal dialysis (PD) patients. Methods:A total of 80 patients with chronic renal failure (CRF) who were admitted in our hospital from November, 2011 to January, 2014 for PD were included in the study and randomized into the treatment group and the control group. The patients in the two groups were routinely performed with PD. The patients in the treatment group were given L-carnitine oral liquid, 10 mL/time, 3 times/d, and telmisartan, 80 mg/time, 1 time/d. The patients in the control group were given L-carnitine oral liquid, 10 mL/time, 3 times a day. The patients in the two groups were treated for 24 weeks continuously. A volume of 5 mL morning fasting venous blood before and after treatment was extracted, and centrifuged for serum. The levels of hs-CRP, IL-6, IL-8, TNF-α, MDA, and GSH-Px were determined.Results:After treatment, the levels of hs-CRP, IL-6, IL-8, and TNF-α were reduced, and the reduced degree in the treatment group was significantly superior to that in the control group. After treatment, MDA was reduced, GSH-Px was elevated, and the reduced degree and elevated degree in the treatment group were significantly superior to those in the control group.Conclusions:Telmisartan in combined with L-carnitine can probably become an ideal therapeutic measure for inhibiting the micro-inflammation state and oxidative stress reaction in PD patients, thus reducing the risk of cardiovascular events, which can provide an evidence for the clinical application in the future.

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

    Directory of Open Access Journals (Sweden)

    Sutirtho Mukhopadhyay

    2011-01-01

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

  14. TNFα blockers and infectious risk in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-06-01

    Full Text Available Patients suffering from rheumatoid arthritis have increased risk of infections when compared with general population. The risk depends directly from disease activity and severity. Furthermore, risk increases with aging, immunosuppressive agents and comorbidities such as diabetes, pulmonary and cardiac diseases. In particular corticosteroids, even at low doses, are a major risk factor. Due to disease related risk it is difficult to separate the risk deriving from the use of TNF alpha blockers. Data from clinical trials, meta-analysis and national registers are somewhat contradictory. In patients with rheumatoid arthritis on routine follow-up, treatment with TNF alpha blockers seems to carry an increased risk of infections compared to traditional DMARDs but not associated with increased risk of overall serious infection. Physicians should carefully monitor for signs of infection when using TNF alpha blockers, particularly shortly after treatment initiation.

  15. Review of topical beta blockers as treatment for infantile hemangiomas.

    Science.gov (United States)

    Painter, Sally L; Hildebrand, Göran Darius

    2016-01-01

    The treatment of infantile hemangiomas changed from the use of oral corticosteroids to oral propranolol on the serendipitous discovery of propanolol's clinical effectiveness in 2008. Since then, clinicians have begun to use topical beta blockers--in particular, timolol maleate 0.5% gel forming solution--with good effect. Topical beta blockers are now used for lesions with both deep and superficial components and those that are amblyogenic. When initiated in the proliferative phase of the lesion, the effectiveness of the treatment can be seen within days. There is no consensus on dosing, treatment bioavailability, or clinical assessment of lesions, but these are topics for future research.

  16. Heart Rate and Cardiovascular Disease: An Alternative to Beta Blockers

    Directory of Open Access Journals (Sweden)

    Michael Liang

    2009-01-01

    Full Text Available Ivabradine, an If inhibitor, acts primarily on the sinoatrial node and is used to reduce the heart rate with minimal effect on myocardial contractility, blood pressure, and intracardiac conduction. Heart rate reduction is an important aspect of care in patients with chronic stable angina and heart failure. Many patients with coronary artery disease have coexisting asthma or chronic obstructive airway disease, and most of them are unable to tolerate beta blockers. Ivabradine may thus be a useful medicine in therapeutic heart rate management especially in patients who are intolerant of beta-blockers.

  17. Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension

    Directory of Open Access Journals (Sweden)

    Takami T

    2012-09-01

    Full Text Available Takeshi Takami,1 Hiroshi Ito,2 Katsuhisa Ishii,3 Kenei Shimada,4 Katsuomi Iwakura,5 Hiroyuki Watanabe,6 Shota Fukuda,7 Junichi Yoshikawa81Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan; 2Department of Cardiovascular Medicine, Okayama University, Graduate School of Medicine, Okayama, Japan; 3Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan; 4Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan; 5Cardiovascular Center, Sakurabashi Watanabe Hospital, Osaka, Japan; 6Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan; 7Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan; 8Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, JapanAbstract: The urinary albumin to creatinine ratio (UACR is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi or angiotensin receptor blocker (ARB to a combination of losartan and hydrochlorothiazide on left ventricular (LV relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024, but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051. Among DM patients, there was a significant relationship between changes in UACR and changes in e′ velocity (r =

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

    Science.gov (United States)

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

    2015-08-01

    Verapamil is used in high doses for the treatment of cluster headache. Verapamil has been described as a P-glycoprotein (P-gp, ABCB1) substrate. We wished to evaluate in vitro whether co administration of a P-gp inhibitor with verapamil could be a feasible strategy for increasing CNS uptake of verapamil. Fluxes of radiolabelled verapamil across MDCK II MDR1 monolayers were measured in the absence and presence of the putative P-gp inhibitor telmisartan (a clinically approved drug compound). Verapamil displayed a vectorial basolateral-to-apical transepithelial efflux across the MDCK II MDR1 monolayers with a permeability of 5.7 × 10(-5) cm sec(-1) compared to an apical to basolateral permeability of 1.3 × 10(-5) cm sec(-1). The efflux could be inhibited with the P-gp inhibitor zosuquidar. Zosuquidar (0.4 μmol/L) reduced the efflux ratio (PB-A/PA-B) for verapamil 4.6-1.6. The presence of telmisartan, however, only caused a slight reduction in P-gp-mediated verapamil transport to an efflux ratio of 3.4. Overall, the results of the present in vitro approach indicate, that clinical use of telmisartan as a P-gp inhibitor may not be an effective strategy for increasing brain uptake of verapamil by co-administration with telmisartan.

  19. Tyrosine kinase blockers: new hope for successful cancer therapy.

    Science.gov (United States)

    Pytel, Dariusz; Sliwinski, Tomasz; Poplawski, Tomasz; Ferriola, Deborah; Majsterek, Ireneusz

    2009-01-01

    Tyrosine kinases (TKs) are attractive targets for cancer therapy, as quite often their abnormal signaling has been linked with tumor development and growth. Constitutive activated TKs stimulate multiple signaling pathways responsible for DNA repair, apoptosis, and cell proliferation. During the last few years, thorough analysis of the mechanism underlying tyrosine kinase's activity led to novel cancer therapy using TKs blockers. These drugs are remarkably effective in the treatment of various human tumors including head and neck, gastric, prostate and breast cancer and leukemias. The most successful example of kinase blockers is Imatinib (Imatinib mesylate, Gleevec, STI571), the inhibitor of Bcr/Abl oncoprotein, which has become a first-line therapy for chronic myelogenous leukemia. The introduction of STI571 for the treatment of leukemia in clinical oncology has had a dramatic impact on how this disease is currently managed. Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva) and Sunitinib (SU 11248, Sutent) specific for VEGF receptor kinase, AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase. The following TK blockers for treatment of various human tumors are in clinical development: Lapatinib (Lapatinib ditosylate, Tykerb, GW-572016), Canertinib (CI-1033), Zactima (ZD6474), Vatalanib (PTK787/ZK 222584), Sorafenib (Bay 43-9006, Nexavar), and Leflunomide (SU101, Arava). Herein, we discuss the chemistry, biological activity and clinical potential of new drugs with tyrosine kinase blockers for cancer treatment.

  20. 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...

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

    CERN Document Server

    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. Photochemical fate of beta-blockers in NOM enriched waters

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-01

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

  3. Structural characterization of three crystalline modifications of telmisartan by single crystal and high-resolution X-ray powder diffraction.

    Science.gov (United States)

    Dinnebier, R E; Sieger, P; Nar, H; Shankland, K; David, W I

    2000-11-01

    Three crystalline modifications (A, B, and C) of 4'-[[2-n-propyl-4-methyl-6-(1-methyl-benzimidazol-2-yl)benzi midazol-1-yl]methyl]biphenyl-2-carboxylic acid (INN name, telmisartan) have been detected and their crystal structures have been determined by single-crystal X-ray diffraction (pseudopolymorph C) and the method of simulated annealing from high-resolution X-ray powder diffraction data (polymorphs A and B). The compound is of interest because of its use as an angiotensin II receptor antagonist. Polymorph A crystallizes in space group P2(I)/c, Z = 4, with unit cell parameters a = 18.7798(3), b = 18.1043(2), and c = 8.00578(7) A, beta = 97.066(1) degrees, and V = 2701.31 A(3). Polymorph B crystallizes in space group P2(I)/a, Z = 4, with unit cell parameters a = 16.0646(5), b = 13.0909(3), and c = 13.3231(3) A, beta = 99.402(1) degrees, and V = 2764.2(1) A(3). The solvated form C crystallizes in space group C2/c, Z = 8, with unit cell parameters a = 30.990(5), b = 13.130(3), and c = 16.381(3) A, beta = 95.02(2) degrees, and V = 6639(2) A(3). For the structure solutions of polymorphs A and B, 13 degrees of freedom (3 translational, 3 orientational, 7 torsion angles) were determined in approximately 2 h of computer time, demonstrating that the crystal packing and the molecular conformation of medium-sized (MW approximately 500) pharmaceutical compounds can now be solved quickly and routinely from high-resolution X-ray powder diffraction data.

  4. Co-milling of telmisartan with poly(vinyl alcohol)--An alkalinizer free green approach to ensure its bioavailability.

    Science.gov (United States)

    Isaac, Jinu; Ganguly, Swastika; Ghosh, Animesh

    2016-04-01

    The aim of this study was to enhance the dissolution and bioavailability of telmisartan (TLM), a poorly water soluble drug by co-milling approach. Physical mixtures of TLM and poly(vinyl alcohol) (PVA) were co-milled in a planetary micro mill in a dry condition by varying process parameters such as drug to polymer weight ratio, ball-to-powder weight ratio, and rotational speed. The co-milled products offered cumulative percentage dissolution of TLM above 75% in 30 min (CG 1 and CG2). These samples were characterized using field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Raman spectra analysis. Well-dispersed acicular shaped particles of TLM were observed in co-milled products. A mixture of crystalline and amorphous TLM with a particle size less than 1 μm was present in CG1. The particle size of TLM observed in CG2 was less than 2 μm. In addition to crystalline and amorphous form of TLM, defective/disordered crystals of TLM were also present in CG 2. Therefore, CG2 tablets exhibited poor stability. CG 1 tablets were found to be stable under accelerated stability test conditions. The relative bioavailability of TLM of CG 1 containing tablets in comparison with Micardis® was 93.92±12.84% (in rabbits). Thus, co-milling of TLM with PVA proves to be a promising "alkalinizer free green approach" to ensure the dissolution and bioavailability of poorly water soluble TLM.

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

    Directory of Open Access Journals (Sweden)

    Hany H Arab

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

  6. Effects of Ramipril and Telmisartan on Plasma Concentrations of Low Molecular Weight and Protein Thiols and Carotid Intima Media Thickness in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Angelo Zinellu

    2016-01-01

    Full Text Available Hypertension, a common feature in chronic kidney disease (CKD, is an independent risk factor for CKD progression and cardiovascular disease. Although inhibitors of the renin-angiotensin system (RAS exert salutary effects on blood pressure control and proteinuria in CKD patients, their activity towards traditional and novel oxidative markers is largely unknown. We studied the effects of 6-month treatment with telmisartan versus a combination of telmisartan and ramipril on plasma concentrations of low molecular mass (LMW, including homocysteine and cysteine and protein thiols (PSH plasma concentration and their relationships with carotid intima media thickness (IMT, in 24 hypertensive CKD patients (age 60±12 years, 8 females and 16 males. Pretreatment PSH concentrations were independently associated with IMT (r=-0.42, p=0.039. Neither treatment affected plasma LMW thiols, in both reduced and total form. By contrast, both treatments increased PSH plasma concentrations and reduced IMT, although significant differences were only observed in the combined treatment group. Our results suggest that the beneficial effects of combined RAS inhibitor treatment on IMT in hypertensive CKD patients may be mediated by a reduction of oxidative stress markers, particularly PSH.

  7. Simultaneous determination of telmisartan and amlodipine in human plasma by LC-MS]MS and its application in a human pharmacokinetic study

    Institute of Scientific and Technical Information of China (English)

    Vasu Babu Ravi; Jaswanth Kumar Inamadugu; Nageswara Rao Pilli; Vudagandla Sreenivasulu; Venkateswarlu Ponnerid

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    M. V. Leonova

    2012-01-01

    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.

  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. 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.

    2012-01-01

    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 investiga

  11. 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....

  12. 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.

  13. Modeling Human Blockers in Millimeter Wave Radio Links

    Institute of Scientific and Technical Information of China (English)

    Jonathan S. Lu; Daniel Steinbach; Patrick Cabrol; Philip Pietraski

    2012-01-01

    In this paper, we investigate the loss caused by multiple humans blocking millimeter wave frequencies. We model human blockers as absorbing screens of infinite height with two knife-edges, We take a physical optics approach to computing the diffraction around the absorbing screens, This approach differs to the geometric optics approach described in much of the literature. The blocking model is validated by measuring the gain from multiple-human blocking configurations on an indoor link. The blocking gains predicted using Piazzi ' s numerical integration method (a physical optics method) agree well with measurements taken from approximately 2.7 dB to -50 dB. Thereofre, this model is suitable for real human blockers, The mean prediction error for the method is approximately -1.2 dB, and the standard deviation is approximately 5 dB.

  14. 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.

  15. 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.

    2016-12-01

    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.

  16. 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...... score of 0, 1--3, 4--8, 9 or higher). RESULTS: 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...

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

    Directory of Open Access Journals (Sweden)

    Jeffrey L Jackson

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

  18. RP-HPLC METHOD FOR SIMULTATANEOUS DETERMINATION OF AMLODIPINE BESYLATE, VALSARTAN, TELMISARTAN, HYDROCHLOROTHIAZIDE AND CHLORTHALIDONE: APPLICATION TO COMMERCIALLY AVAILABLE DRUG PRODUCTS

    Directory of Open Access Journals (Sweden)

    R. A. Mhaske et al.

    2012-01-01

    Full Text Available A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous determination of anti-hypertensive drugs Amlodipine Besylate, Valsartan, Telmisartan and diuretics Hydrochlorothiazide and Chlorthalidone. The separation was achieved on Cosmosil PAQ (150 mm × 4.6 mm 5 μm column with gradient flow. The mobile phase at a flow rate of 1.0 mL min−1 consisted of 0.05 M sodium dihydrogen phosphate buffer and acetonitrile (Gradient ratio. The UV detection was carried out at 220 nm. The method was successfully validated in accordance to ICH guidelines. Further, the validated method was applied for commercially available pharmaceutical dosage form.

  19. Angiotensin receptors and actions in guinea pig enteric nervous system.

    Science.gov (United States)

    Wang, Guo-Du; Wang, Xi-Yu; Hu, Hong-Zhen; Fang, Xiu-Cai; Liu, Sumei; Gao, Na; Xia, Yun; Wood, Jackie D

    2005-09-01

    Actions of ANG II on electrical and synaptic behavior of enteric neurons in the guinea pig small intestine were studied. Exposure to ANG II depolarized the membrane potential and elevated neuronal excitability. The number of responding neurons was small, with responses to ANG II in 32% of submucosal neurons and 25% of myenteric neurons. Hyperpolarizing responses were evoked by ANG II in 45% of the neurons. The hyperpolarizing responses were suppressed by alpha2-noradrenergic receptor antagonists, which suggested that the hyperpolarizing responses reflected stimulation of norepinephrine release from sympathetic neurons. Exposure to ANG II enhanced the amplitude and prolonged the duration of noradrenergic inhibitory postsynaptic potentials and suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. The selective ANG II(1) receptor (AT1R) antagonists, ZD-7115 and losartan, but not a selective AT2R antagonist (PD-123319), suppressed the actions of ANG II. Western blot analysis and RT-PCR confirmed expression of AT1R protein and the mRNA transcript for the AT1R in the enteric nervous system. No expression of AT2R protein or mRNA was found. Immunoreactivity for AT1R was expressed by the majority of neurons in the gastric antrum and small and large intestine. AT1R immunoreactivity was coexpressed with calbindin, choline acetyltransferase, calretinin, neuropeptide Y, and nitric oxide synthase in subpopulations of neurons. The results suggest that formation of ANG II might have paracrine-like actions in the enteric nervous system, which include alterations in neuronal excitability and facilitated release of norepinephrine from sympathetic postganglionic axons. The enhanced presence of norepinephrine is expected to suppress fast and slow excitatory neurotransmission in the enteric microcircuits and to suppress neurogenic mucosal secretion.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hossein Babaei

    2011-06-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    -DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed......BACKGROUND: The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist...... telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. METHODS: Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER...

  3. Increased serum potassium affects renal outcomes

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  4. 厄贝沙坦和替米沙坦降血压作用的Meta分析%A Meta Analysis of Irbesartan and Telmisartan in Lowering Blood Pressure

    Institute of Scientific and Technical Information of China (English)

    张彩霞; 韩本高

    2016-01-01

    目的:通过Meta分析探讨厄贝沙坦和替米沙坦降血压作用的疗效和安全性。方法检索万方数字化期刊、维普中文科技期刊数据库有关两药降血压作用的临床随机对照研究,筛选、评价文献提取有效数据进行 Meta分析。结果显效率、有效率、总有效率、无效率和不良反应均无统计学意义。结论厄贝沙坦和替米沙坦降血压作用疗效和安全性相当。%OBJECTIVE To explore the efficacy and safety of irbesartan and telmisartan in lowering blood pres-sure by Meta analysis.METHODS Retrieve randomized controlled trials of irbesartan and telmisartan in lowering blood pressure from Wanfang Data knowledge service platform and VIP journals integrated service platform, and screen,evaluate the literature,thenextracte data for Meta analysis.RESULTS Excellent effective rate,general effec-tive rate, total effective rate, ineffective rate and adverse reactions had no statistically significant differ-ence.CONCLUSION the efficacy and safety of irbesartan and telmisartan almost the same.

  5. 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....

  6. Kinetic Hairpin Oligonucleotide Blockers for Selective Amplification of Rare Mutations

    Science.gov (United States)

    Jia, Yanwei; Sanchez, J. Aquiles; Wangh, Lawrence J.

    2014-01-01

    Detection of rare mutant alleles in an excess of wild type alleles is increasingly important in cancer diagnosis. Several methods for selective amplification of a mutant allele via the polymerase chain reaction (PCR) have been reported, but each of these methods has its own limitations. A common problem is that Taq DNA polymerase errors early during amplification generate false positive mutations which also accumulate exponentially. In this paper, we described a novel method using hairpin oligonucleotide blockers that can selectively inhibit the amplification of wild type DNA during LATE-PCR amplification. LATE-PCR generates double-stranded DNA exponentially followed by linear amplification of single-stranded DNA. The efficiency of the blocker is optimized by adjusting the LATE-PCR temperature cycling profile. We also demonstrate that it is possible to minimize false positive signals caused by Taq DNA polymerase errors by using a mismatched excess primer plus a modified PCR profile to preferentially enrich for mutant target sequences prior to the start of the exponential phase of LATE-PCR amplification. In combination these procedures permit amplification of specific KRAS mutations in the presence of more than 10,000 fold excess of wild type DNA without false positive signals. PMID:25082368

  7. Role of β-blocker therapy in pediatric heart failure.

    Science.gov (United States)

    Patel, Akash R; Shaddy, Robert E

    2010-01-01

    Heart failure is becoming an increasingly common and significant problem in the field of pediatric cardiology. The numerous types of cardiomyopathies, and more recently, long-term survival of patients with congenital heart disease, have added to a growing patient population. Over the last several decades, our knowledge base regarding mechanisms of disease and therapeutic intervention in adult patients with heart failure has drastically changed. The most recent and important breakthrough in the pharmacologic treatment of heart failure has been the particular role of β-blocker therapy. This medication has led to significant improvements in survival and symptoms in adults, with less convincing findings in limited studies in pediatrics. The ability to study the benefits of this therapy in patients has been challenging owing to the heterogeneity of the patient population and lack of large sample sizes. However, as we investigate the mechanisms behind the disease process, the differences that exist between disease conditions and ages, and the significant alterations that may exist at the molecular and genetic level, our understanding of β-blocker therapy in pediatric heart failure will improve, and ultimately may lead to patient-specific therapy.

  8. End organ protection by calcium-channel blockers.

    Science.gov (United States)

    Tzivoni, D

    2001-02-01

    In recent years, much attention has been given to end organ protection by antihypertensive, anti-heart failure, and anti-ischemic medications. This review describes the available information on end organ protection by calcium-channel blockers (CCBs). In normotensive patients and patients with hypertension treated with long-acting dihydropyridines, medial thickness was thinner than in patients treated with atenolol or in untreated hypertensive patients. Long-term treatment was associated with significant reduction in left ventricular mass. Calcium-channel blockers also improved endothelial-dependent relaxation and reversed the vasoconstrictive response to nitric oxide inhibitors. In diabetic patients, CCBs were effective in preserving kidney function and microalbuminurea. The combination of angiotensin-converting enzyme (ACE) inhibitors and CCBs was more effective than ACE inhibitors alone in preserving kidney function. In animal experiments, CCBs prevented development of coronary atheroschlerosis; however, in humans only limited data are available on their antiatherogenic effect. Some studies suggest that CCBs exert antiplatelets properties and may therefore be beneficial in patients with coronary artery disease.

  9. 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.

  10. 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.

  11. 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.

  12. Impact of Beta-Blockers on Nonhead Injured Trauma Patients.

    Science.gov (United States)

    Hendrick, Leah E; Schroeppel, Thomas J; Sharpe, John P; Alsbrook, Diana; Magnotti, Louis J; Weinberg, Jordan A; Johnson, Benjamin P; Lewis, Richard H; Clement, L Paige; Croce, Martin A; Fabian, Timothy C

    2016-07-01

    Catecholamine surge after traumatic injury may lead to dysautonomia with increased morbidity. Small retrospective studies have shown potential benefit of beta-blockers (BB) in trauma patients with and without traumatic brain injury (TBI). This study evaluates a large multiply injured cohort without TBI that received BB. Patients were identified from the trauma registry from January 1, 2003 to December 31, 2011. Patients who received >1 dose of BB were compared to controls. Patients with TBI, length of stay (LOS) ratio (OR) 0.952; confidence interval (CI) 0.620-1.461]. In conclusion, in this largest study to date, patients receiving BB were older, more severely injured, and had a higher mortality. Unlike TBI patients, multivariable regression showed no benefit from BB in this population.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. A review on the putative association between beta-blockers and depression

    NARCIS (Netherlands)

    Verbeek, D.E.; van Riezen, J.; de Boer, R.A.; van Melle, J.P.; de Jonge, P.

    2011-01-01

    Several kinds of systematic studies have been conducted verifying the putative association between beta-blockers and depressive symptoms. However, many of these studies had important limitations in their design. In most of the studies, no effect of beta-blockers on depressive symptoms was seen. Beca

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  17. 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....

  18. 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....

  19. 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 qualit

  20. [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 add

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

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2013-01-01

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

  2. Choice of Intravenous Agents and Intubation Neuromuscular Blockers by Anesthesia Providers

    Science.gov (United States)

    1996-09-01

    nondepolarizing muscle blockers (Omoigui, 1995). 8 Neuromuscular Blockers Atracurium is a nondepolarizing skeletal muscle relaxant and its...vecuronium. Feldman (1994) and Wicks (1994) report that rocuronium has the most rapid onset of any other nondepolarizing muscle relaxant with...prolonged muscle relaxant block at usual intubation doses. Mirakhur (1994) and Robertson, Hull, Verbeek, 8L Bonjii (1994) report minimal changes in

  3. Combining other antihypertensive drugs with β-blockers in hypertension: a focus on safety and tolerability.

    Science.gov (United States)

    Richards, Tiffany R; Tobe, Sheldon W

    2014-05-01

    Combining multiple classes of antihypertensive drugs together is one of the most important factors for achieving blood pressure control in most hypertensive patients. The benefits of combination therapy in comparison with monotherapy include: a synergistic enhancement of each drug's hypertensive effects and a potential reduction of side effects if each drug is used at a lower dose. Although long-acting dihydropyridine calcium channel blockers and β-blockers are a good fit for combination therapy, because of the risk of atrioventricular block and bradycardia, the combination of verapamil and β-blockers is not advised. In addition, the combination of higher-dose diltiazem and β-blockers is also not advised. β-blockers and diuretic agents as initial lone combination therapy are not the preferred combination to be used in uncomplicated hypertension. Using an angiotensin-converting enzyme inhibitor as initial combination therapy with most β-blockers is not recommended because of a lack of antihypertensive efficacy. Nebivolol, however, appears different in this regard and might provide an opportunity for combining these 2 classes of agents with proven cardiovascular benefits for better blood pressure control. Adding an α-blocker to a β-blocker is an effective combination.

  4. 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

  5. An investigation into sustainable construction stimulators and blockers

    Directory of Open Access Journals (Sweden)

    M Osmani

    2014-10-01

    Full Text Available The UK Government has been using a combination of regulation, economic instruments and voluntary agreements to meet targets of ethical, social and environmental performancein driving the climate change agenda. The UK is the first country worldwide to set a legally binding 80% greenhouse-gas emissions reduction target by 2050. The built environment in the UK is responsible for about 40% of carbon emissions, 32% of solid waste generation,20% of water effluents, and 40% of all energy used. As such, the construction industry has been targeted to facilitate the transition to a low-carbon economy.Indeed, sustainabilitywithin the built environment has become the forefront of all sustainable development policies in the UK. However; various studies have outlined the difficulty of translating theUK’s 80% greenhouse-gas emissions reduction target to a micro level such as construction projects. This research engaged the top 100 UK contractorsto investigate stimulators that drivethe implementation of sustainability in their projects,and assess associated blockers.Findings reveal that sustainability requirements driven by financial and business were viewed by participating contractors as being the key motivators in construction projects. Corporate Social Responsibility (CSR was viewed as a vehicle to improve social and environmental dynamics of sustainability through local community support initiatives,which in turn has increased companies’ opportunities to secure new projects, particularly from public clients. On the other hand, respondents called for clearer and inclusivelegislation; increased awareness; enhanced communication and coordination among project stakeholders; and widespread sharing and dissemination of sustainableconstruction best practice data.Keywords: UK; contractors; sustainable construction; stimulators; blockers.

  6. A potent potassium channel blocker from Mesobuthus eupeus scorpion venom.

    Science.gov (United States)

    Gao, Bin; Peigneur, Steve; Tytgat, Jan; Zhu, Shunyi

    2010-12-01

    Scorpion venom-derived peptidyl toxins are valuable pharmacological tools for investigating the structure-function relationship of ion channels. Here, we report the purification, sequencing and functional characterization of a new K(+) channel blocker (MeuKTX) from the venom of the scorpion Mesobuthus eupeus. Effects of MeuKTX on ten cloned potassium channels in Xenopus oocytes were evaluated using two-electrode voltage-clamp recordings. MeuKTX is the orthologue of BmKTX (α-KTx3.6), a known Kv1.3 blocker from the scorpion Mesobuthus martensii, and classified as α-KTx3.13. MeuKTX potently blocks rKv1.1, rKv1.2 and hKv1.3 channels with 50% inhibitory concentration (IC(50)) of 203.15 ± 4.06 pM, 8.92 ± 2.3 nM and 171 ± 8.56 pM, respectively, but does not affect rKv1.4, rKv1.5, hKv3.1, rKv4.3, and hERG channels even at 2 μM concentration. At this high concentration, MeuKTX is also active on rKv1.6 and Shaker IR. Our results also demonstrate that MeuKTX and BmKTX have the same channel spectrum and similar pharmacological potency. Analysis of the structure-function relationships of α-KTx3 subfamily toxins allows us to recognize several key sites which may be useful for designing toxins with improved activity on hKv1.3, an attractive target for T-cell mediated autoimmune diseases.

  7. 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

    OBJECTIVES: 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. METHODS: 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...

  8. 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

  9. Shortening baroreflex delay in hypertrophic cardiomyopathy patients – an unknown effect of β-blockers

    Science.gov (United States)

    Katarzynska-Szymanska, Agnieszka; Ochotny, Romuald; Oko-Sarnowska, Zofia; Wachowiak-Baszynska, Hanna; Krauze, Tomasz; Piskorski, Jaroslaw; Gwizdala, Adrian; Mitkowski, Przemyslaw; Guzik, Przemyslaw

    2013-01-01

    Aims Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and impaired diastolic and systolic function. Abnormal sympathetic–parasympathetic balance is a potential stimulus for left ventricular hypertrophy in HCM patients. β-Blockers are routinely used in HCM for their strong negative inotropic effect; however, these drugs also influence the sympathetic–parasympathetic balance. This study aimed to determine the autonomic control of the cardiovascular system and the autonomic effects of β-blockers in HCM patients treated or untreated with β-blockers. Methods Among 51 HCM outpatients (18–70 years old; 29 men) there were 19 individuals with no medication and 32 subjects treated with a β-blocker. Fourteen age- and gender-matched (23–70 years old; nine men) healthy volunteers were enrolled in the control group. Continuous, non-invasive finger blood pressure was recorded during supine rest for 30 min. Autonomic regulation of the cardiovascular system was measured by heart rate variability and spontaneous baroreflex function (cross-correlation sequence method). Results The mean pulse interval, time domain and spectral measures of heart rate variability and baroreflex sensitivity were comparable between HCM patients, treated or not with β-blockers, and the control group. However, the delay of the baroreflex was significantly longer in HCM patients who were not treated with β-blockers [2.0 (1.6–2.3) s] in comparison with HCM patients receiving β-blockers [1.4 (1.1–1.8) s; P = 0.0072] or control subjects [1.2 (0.8–1.8) s; P = 0.0025]. This delay did not differ between HCM patients treated with β-blockers and the control group. Conclusions Hypertrophic cardiomyopathy not treated with β-blockers is accompanied by prolonged baroreflex delay. The use of β-blockers normalizes this delay. PMID:23126403

  10. Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model.

    Science.gov (United States)

    Narita, Yuki; Ueda, Miki; Uchimura, Kohei; Kakizoe, Yutaka; Miyasato, Yoshikazu; Mizumoto, Teruhiko; Morinaga, Jun; Hayata, Manabu; Nakagawa, Terumasa; Adachi, Masataka; Miyoshi, Taku; Sakai, Yoshiki; Kadowaki, Daisuke; Hirata, Sumio; Mukoyama, Masashi; Kitamura, Kenichiro

    2016-02-01

    We previously reported that camostat mesilate (CM) had renoprotective and antihypertensive effects in rat CKD models. In this study, we examined if CM has a distinct renoprotective effect from telmisartan (TE), a renin-angiotensin-aldosterone system (RAS) inhibitor, on the progression of CKD. We evaluated the effect of CM (400 mg/kg/day) and/or TE (10 mg/kg/day) on renal function, oxidative stress, renal fibrosis, and RAS components in the adenine-induced rat CKD model following 5-weeks treatment period. The combination therapy with CM and TE significantly decreased the adenine-induced increase in serum creatinine levels compared with each monotherapy, although all treatment groups showed similar reduction in blood pressure. Similarly, adenine-induced elevation in oxidative stress markers and renal fibrosis markers were significantly reduced by the combination therapy relative to each monotherapy. Furthermore, the effect of the combination therapy on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was similar to that of TE monotherapy, and CM had no effect on both PRA and PAC, suggesting that CM has a distinct pharmacological property from RAS inhibition. Our findings indicate that CM could be a candidate drug for an add-on therapy for CKD patients who had been treated with RAS inhibitors.

  11. The effect of mechanical grinding on the formation, crystalline changes and dissolution behaviour of the inclusion complex of telmisartan and β-cyclodextrins.

    Science.gov (United States)

    Borba, Paola Aline Amarante; Pinotti, Marihá; Andrade, George Ricardo Santana; da Costa, Nivan Bezerra; Olchanheski Junior, Luiz Renato; Fernandes, Daniel; de Campos, Carlos Eduardo Maduro; Stulzer, Hellen Karine

    2015-11-20

    Telmisartan (TEL) was entrapped into β-cyclodextrin aiming the improvement of its biopharmaceutical properties of low solubility. A solid state grinding process was used to prepare the molecular inclusion complex (MIC) for up to 30min. The inclusion ratio of drug and β-cyclodextrin was established as 1:2 and 1:3 (mol/mol) by phase solubility study and Job Plot. DSC, XRPD and FTIR confirmed the molecular interactions between TEL and β-cyclodextrin. Computer molecular modeling supports the presence of hydrogen bonds between guest and host and demonstrated the most probable complexes configuration. MIC_1:2_30 and MIC_1:3_30 enhanced the dissolution rate of the drug achieving a delivery rate comparable with the reference medicine available in the market (81% and 87% in 5min, for MIC_1:3_30 and Micardis(®), respectively). These formulations showed rapid and effective antihypertensive effect against angiotensin II in rats up to 180min, with statistically significant results against placebo and control in the first 30min after administration.

  12. Not All Beta-Blockers Are Equal in the Management of Long QT Syndrome Types 1 and 2

    NARCIS (Netherlands)

    Chockalingam, Priya; Crotti, Lia; Girardengo, Giulia; Johnson, Jonathan N.; Harris, Katy M.; van der Heijden, Jeroen F.; Hauer, Richard N. W.; Beckmann, Britt M.; Spazzolini, Carla; Rordorf, Roberto; Rydberg, Annika; Clur, Sally-Ann B.; Fischer, Markus; van den Heuvel, Freek; Kaeaeb, Stefan; Blom, Nico A.; Ackerman, Michael J.; Schwartz, Peter J.; Wilde, Arthur A. M.

    2012-01-01

    Objectives The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Background Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equ

  13. 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

  14. Pulmonary vasoconstrictor action of KCNQ potassium channel blockers

    Directory of Open Access Journals (Sweden)

    Balan Prabhu

    2006-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Gary C Kessler

    2014-09-01

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

  16. Flow-injection-enhanced chemiluminescence method for the determination of three β-blockers

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To develop a rapid,simple and sensitive chemiluminescence method for the determination of three β-blockers (bisoprolol,atenolol and propranolol). Methods The chemiluminescence of cerium (Ⅳ)-sulfite system was obviously sensitized by adding anyone of three β-blockers in acid media. A new chemiluminescence method was set up by combining with flow-injection technique and used to determine the three β-blockers. Results Good linear ranges were obtained at the concentrations of 2.0×10-7g/mL-4.0×10-5g/mL...

  17. 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...... and angina in the reperfusion era appeared to be short-term (30-days). CONCLUSIONS: In contemporary practice of treatment of myocardial infarction, â-blockers have no mortality benefit but reduce recurrent myocardial infarction and angina (short-term) at the expense of increase in heart failure, cardiogenic...

  18. The clinical observation of telmisartan combined kidney convalescent to treat diabetic nephropathy%替米沙坦联合肾复康片治疗糖尿病肾病的临床观察

    Institute of Scientific and Technical Information of China (English)

    高君

    2013-01-01

    Objective Analyze and study the curative effect of telmisartan combined kidney convalescent to treat diabetic nephropathy .Method Choose 160 cases of patients with high blood pressure at our hospital,according to the different method of treatment,they will be divided into two groups.Treatment with the control group only telmisartan,kidney within the experimental group is used with telmisartan combination therapy.Compare and observe effect of two groups of patients after treatment.Re-sult Experimental group were controlled by various indicators total efficiency(87.50%)was significantly higher(57.50%),statistically significant(P<0.05).Conclu-sion Using renal convalescent piece with telmisartan approach in the treatment of diabetic nephropathy have important applied value ,can effectively prevent the develop-ment of diabetic nephropathy,promote the recovery of patients with renal function,and less adverse reaction,can be widely used in clinical.%目的:关于将肾复康片与替米沙坦联合用于治疗糖尿病肾病所取得的疗效进行分析研究。方法选取到我院接受治疗的患有高血压的患者160例,按治疗方法的不同将其分成两组。对照组仅采用替米沙坦治疗,实验组则采用肾复康片与替米沙坦联合治疗。比较并观察两组患者经治疗后取得的效果。结果实验组患者各项指标控制的总有效率(87.50%)明显高于对照组(57.50%),统计学上有意义(P<0.05)。结论采用肾复康片与替米沙坦联合的方式在糖尿病肾病的治疗中有重要的应用价值,能有效阻止糖尿病肾病的发展,促进患者肾功能的恢复,且不良反应少,在临床上可以广泛运用。

  19. 复方丹参滴丸联合替米沙坦治疗糖尿病肾病临床观察%Compound salvia pellet combined with telmisartan in the treatment of diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    王康君; 文世林

    2009-01-01

    Objective To observe the combined treatment effect of compound salvia pellet and telmisartan on dia-betic nephropathy (DN). Methods Sixty-three clinical diabetes subjects with complications of DN were randomly divided into treatment group and control group. Both groups received basic diabetes therapy such as strict blood control, low salt and low protein diet. The control group was simply given telmisartan. Besides telmisartan, the treatment group further received compound salvia pellet treatment. After 6 months treatment, 24 h urinary albumin (uAlb), serum creatinine (Ccr) and fundus oculi were examined. Results uAlb and uAlb/Ccr was significantly reduced in both. groups. However, the reduction was much larger in treatment group than in control group(P<0.01), DN was markedly improved in both groups and the treatment group improved more significantly than control group. No side effect was observed on all the subjects in the treatment process. Conclusions Combined treatment of compound salvia pellet and telmisartan on DN is effective and safe and the combination deserves further clinical applications.%目的 观察复方丹参滴丸联合替米沙坦治疗糖尿病肾病(DN)的疗效.方法 将63例临床DN患者随机分为治疗组和对照组,两组均严格控制血糖,给予低盐、低蛋白饮食等基础治疗,对照组单纯使用替米沙坦,治疗组在替米沙坦的基础上联合复方丹参滴丸治疗6个月.观察24 h尿白蛋白(uAlb)、血肌酐(Ccr)变化.结果 两组患者uAlb和尿白蛋白/肌酐(uAlb/Ccr)比值均较治疗前显著下降,而治疗组下降显著高于对照组(P<0.01),治疗过程中无明显不良反应.结论 复方丹参滴丸联合替米沙坦治疗DN安全、高效,值得临床推广应用.

  20. 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

  1. Beta blockers and the sensitivity of the thallium treadmill test

    Energy Technology Data Exchange (ETDEWEB)

    Martin, G.J.; Henkin, R.E.; Scanlon, P.J.

    1987-09-01

    The effect beta blockers (BB) may have on the sensitivity of the thallium treadmill test (Th-TMT) is controversial. The purpose of this study was to test the hypothesis that BB decrease the sensitivity of the Th-TMT. Two hundred three patients over a two-year period were identified who satisfied the following criteria. All had symptom-limited upright treadmill exercise tests with stress and redistribution thallium imaging, as well as coronary angiography within two months of the Th-TMT. Of 58 patients with CAD not on BB, 52 had an abnormal Th-TMT scan (sensitivity 90 percent). In comparison, the sensitivity of the Th-TMT scan in the 88 patients with CAD receiving BB was 76 percent (p less than 0.05). We conclude that BB may significantly decrease the sensitivity of the Th-TMT. Physicians should fully appreciate the higher false negative rate (24 vs 10 percent) for patients on BB and consider cautious withdrawal prior to diagnostic studies.

  2. Golimumab, the newest TNF-α blocker, comes of age.

    Science.gov (United States)

    Papagoras, Charalampos; Voulgari, Paraskevi V; Drosos, Alexandros A

    2015-01-01

    Golimumab, a fully human monoclonal antibody against tumour necrosis factor-α (TNF-α) is one of the newest biologics that has become available for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Following the initial randomised double-blind placebo-controlled clinical trials, which demonstrated the efficacy and safety of the drug in the context of a limited patient sample and a relatively short time frame, golimumab has been the focus of continuous investigation through the extensions of the above-mentioned trials, new clinical trials and registries of biologic drug use in daily clinical practice. The review of this data and their inclusion in meta-analyses and indirect comparisons across TNF-α blockers suggest that golimumab possesses similar properties regarding efficacy and safety as the older monoclonal anti-TNF-α antibodies. The novelty of golimumab is perhaps its dosing regimen, i.e. subcutaneous self-administration once monthly, which allows for the least disturbance in the life of patients.

  3. Taste acceptability of pulverized brand-name and generic drugs containing amlodipine or candesartan.

    Science.gov (United States)

    Uestuener, Peter; Ferrarini, Alessandra; Santi, Maristella; Mardegan, Chiara; Bianchetti, Mario G; Simonetti, Giacomo D; Milani, Gregorio P; Lava, Sebastiano A G

    2014-07-01

    Trials with pulverized brand-name antihypertensive drugs suggest that, from the perspective of taste acceptability, crushed candesartan, chlortalidon, hydrochlorothiazide, lercanidipine and lisinopril should be preferred to pulverized amlodipine, atenolol, bisoprolol, enalapril, irbesartan, losartan, ramipril, telmisartan and valsartan. Brand-name antihypertensive drugs and the corresponding generic medicines have never been compared with respect to their taste acceptability. We therefore investigated among healthy health care workers the taste acceptability of a pulverized 1 mg-test dose of the brand-name and two generics containing either the dihydropyridine calcium-channel blocker amlodipine (Norvasc(®), Amlodipin-Mepha(®) and Amlodipin Pfizer(®)) or the angiotensin receptor antagonist candesartan (Atacand(®), Cansartan-Mepha(®) and Pemzek(®)). For this purpose, a smiley-face scale depicting four degrees of pleasure was used. Between November and December 2013, the taste test was performed among 19 nurses (15 female and 4 male subjects) and 12 physicians (5 female and 7 male subjects) aged between 25 and 49 years. Pulverized brand-names and generics containing either amlodipine or candesartan did not differ with respect to their taste acceptability.

  4. 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.

  5. Effects of changing the type of H2-blocker in the treatment of H2-blocker-resistant ulcers: comparison of roxatidine acetate hydrochloride and other H2-blockers.

    Science.gov (United States)

    Yasutake, K; Amano, M; Mizokami, Y; Kubota, S; Fukumoto, H; Imamura, Y; Yokoya, H; Irie, K

    1998-01-01

    The efficacy of switching from one type of H2-receptor antagonist (H2-blocker) to another, in the treatment of H2-blocker-resistant ulcers was investigated using H2-blockers with five-membered rings (five-membered-ring agents)--such as cimetidine, ranitidine and famotidine--and an H2-blocker with a six-membered ring, roxatidine. By switching from a five-membered-ring agent to roxatidine in the treatment of five-membered-ring resistant ulcers (study I), gastric ulcers were healed in nine of 19 patients (47%) and duodenal ulcers were healed in eight of nine patients (89%). By switching from roxatidine to one of the five-membered-ring agents in the treatment of roxatidine-resistant ulcers (study II), gastric ulcer was healed in six of 15 patients (40%), and duodenal ulcer was healed in 4 of 10 patients (40%). Particularly in the case of duodenal ulcers, the switch to treatment with roxatidine, which has a different chemical structure from the five-membered-ring agents, may be useful in the treatment of five-membered-ring-resistant ulcers.

  6. 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

    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...

  7. The current status of beta blockers' use in the management of hypertension.

    Science.gov (United States)

    Akbar, Shahid; Alorainy, Mohammad S

    2014-11-01

    The invention of beta (β)-blockers culminated in a new era in the treatment of cardiovascular diseases (CD), and changed the course of pharmacology research for years to come. Since the introduction of propranolol into clinical practice in 1964, β-blockers enjoyed a special place in the clinicians' armamentarium against CDs, especially for patients with ischemic heart diseases, and are still one of the most extensively used therapeutic drugs in both cardiac and non-cardiac ailments. Current uses of β-blockers in CDs include ischemic heart diseases, hypertension, cardiac arrhythmias, and heart failure. Other substantial non-cardiac uses include glaucoma, migraine, situational anxiety, benign essential tremors, and cardiac symptoms of thyrotoxicosis. This review covers some of the evolutionary changes of clinical uses of β-blockers, the rationale for their use, some recent controversies surrounding their use for treatment of hypertension, and advantages of newer additions to the group. 

  8. 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...

  9. 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...

  10. 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......-varying Cox regression models to determine the hazard ratio (HR) associated with beta-blocker treatment and used treatment-by-covariate interaction tests (pint) to determine whether the association differed for patients with or without a recent MI. RESULTS: A total of 26,793 patients were included, 19...

  11. 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....

  12. Modeling of the Binding of Peptide Blockers to Voltage-Gated Potassium Channels: Approaches and Evidence.

    Science.gov (United States)

    Novoseletsky, V N; Volyntseva, A D; Shaitan, K V; Kirpichnikov, M P; Feofanov, A V

    2016-01-01

    Modeling of the structure of voltage-gated potassium (KV) channels bound to peptide blockers aims to identify the key amino acid residues dictating affinity and provide insights into the toxin-channel interface. Computational approaches open up possibilities for in silico rational design of selective blockers, new molecular tools to study the cellular distribution and functional roles of potassium channels. It is anticipated that optimized blockers will advance the development of drugs that reduce over activation of potassium channels and attenuate the associated malfunction. Starting with an overview of the recent advances in computational simulation strategies to predict the bound state orientations of peptide pore blockers relative to KV-channels, we go on to review algorithms for the analysis of intermolecular interactions, and then take a look at the results of their application.

  13. Pseudosaccharin amines as potent and selective KV1.5 blockers.

    Science.gov (United States)

    Lloyd, John; Finlay, Heather J; Kover, Alexander; Johnson, James; Pi, Zulan; Jiang, Ji; Neels, James; Cavallaro, Cullen; Wexler, Ruth; Conder, Mary Lee; Shi, Hong; Li, Danshi; Sun, Huabin; Chimalakonda, Anjaneya; Huang, Christine; Salvati, Mark; Levesque, Paul

    2015-11-01

    Phenethyl aminoheterocycles like compound 1 were known to be potent I(Kur) blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent K(V)1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects.

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

    Directory of Open Access Journals (Sweden)

    Agarwal Pankaj

    2007-01-01

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

  15. Effect of different beta blockers on penile vascular velocities in hypertensive males

    OpenAIRE

    Samer Malak Botros; Ahmed Mohamed Hussein; Ahmed Shawky Elserafy

    2015-01-01

    Background: Beta blockers are very commonly used as antihypertensive medications in young active individuals. This class has been accused of erectile dysfunction in patients taking them. Problems with erectile function can raise a concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. Aim: The aim was to assess the effect of different beta blockers: nebivolol, atenolol, bisoprolol, and carvedilol on the penile arteria...

  16. 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....

  17. Dihydropyridine type calcium channel blocker-induced turbid dialysate in patients undergoing peritoneal dialysis.

    Science.gov (United States)

    Yoshimoto, K; Saima, S; Nakamura, Y; Nakayama, M; Kubo, H; Kawaguchi, Y; Nishitani, H; Nakamura, Y; Yasui, A; Yokoyama, K; Kuriyama, S; Shirai, D; Kugiyama, A; Hayano, K; Fukui, H; Horigome, I; Amagasaki, Y; Tsubakihara, Y; Kamekawa, T; Ando, R; Tomura, S; Okamoto, R; Miwa, S; Koyama, T; Echizen, H

    1998-08-01

    We previously reported that manidipine, a new dihydropyridine type calcium channel blocker, produced chylous peritoneal dialysate being visually indistinguishable from infective peritonitis in 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) [Yoshimoto et al. 1993]. To study whether such an adverse drug reaction would also be elicited by other commonly prescribed calcium channel blockers in CAPD patients, we have conducted postal inquiry to 15 collaborating hospitals and an institutional survey in International Medical Center of Japan as to the possible occurrence of calcium channel blocker-associated non-infective, turbid peritoneal dialysate in CAPD patients. Our diagnostic criteria for drug-induced turbidity of dialysate as a) it developed within 48 h after the administration of a newly introduced calcium channel blocker to the therapeutic regimen, b) absence of clinical symptoms of peritoneal inflammation (i.e., pyrexia, abdominal pain, nausea or vomiting), c) the fluid containing normal leukocyte counts and being negative for bacterial and fungal culture of the fluid, and d) it disappeared shortly after the withdrawal of the assumed causative agent. Results showed that 19 out of 251 CAPD patients given one of the calcium channel blockers developed non-infective turbid peritoneal dialysis that fulfilled all the above criteria. Four calcium channel blockers were suspected to be associated with the events: benidipine [2 out of 2 (100%) patients given the drug], manidipine [15 out of 36 (42%) patients], nisoldipine [1 out of 11 (9%) patients] and nifedipine [1 out of 159 (0.6%)] in descending order of frequency. None of the patients who received nicardipine, nilvadipine, nitrendipine, barnidipine and diltiazem (25, 7, 2, 1 and 8 patients, respectively) exhibited turbid dialysate. In conclusion, we consider that certain dihydropyridine type calcium channel blockers would cause turbid peritoneal dialysate being similar to that observed in

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

    Directory of Open Access Journals (Sweden)

    Julie A Mennella

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

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

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    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

  20. Beta-blocker use and COPD mortality: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    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.

  1. Comparative effects of three beta blockers (atenolol, metoprolol, and propranolol) on survival after acute myocardial infarction.

    Science.gov (United States)

    Gottlieb, S S; McCarter, R J

    2001-04-01

    The beneficial impact of beta blockade after an acute myocardial infarction (AMI) is clear, but beta-adrenergic blockers differ in multiple characteristics, including lipophilicity and selectivity. The impact of these factors on the effects of beta blockade is unknown. We therefore compared the effects of different beta blockers on mortality after AMI. Charts of 201,752 patients with AMI were abstracted by the Cooperative Cardiovascular Project, a quality assurance program sponsored by the Health Care Financing Administration. Of the 69,338 patients prescribed beta blockers, we compared mortality of patients receiving different beta-adrenergic blockers using the Cox proportional-hazards model accounting for multiple factors that might influence survival. The mortality rates of the 2 selective agents, metoprolol and atenolol, were virtually identical (13.5% and 13.4% 2-year mortality, respectively). Compared with metoprolol, patients discharged on propranolol had a slightly increased mortality (15.9% 2-year mortality), which may be related to undetected differences at baseline. Survival with all of the drugs was superior to the 23.9% 2-year mortality seen in patients not receiving beta blockers. Beta blockade overall was associated with a 40% improvement in survival. Although the use of beta blockade after AMI has major prognostic importance, the present study suggests that the specific beta blocker chosen will have little influence on mortality.

  2. Roles of MgO release from polyethylene glycol 6000-based solid dispersions on microenvironmental pH, enhanced dissolution and reduced gastrointestinal damage of telmisartan.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Seung Aeon; Nho, Vo Hong; Chi, Sang-Cheol; Lee, Beom-Jin

    2011-05-01

    The roles of magnesium oxide (MgO) release from solid dispersions (SDs) in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and water were investigated to elucidate the enhanced dissolution and reduced intestinal damages of telmisartan as a model drug. The polyethylene glycol 6000 (PEG 6000) was used to prepare the SDs. Three SDs were prepared: SD1 (PEG, MgO, TEL), SD2 (PEG 6000, TEL), SD3 (MgO, TEL). The physical mixture (PM) consisting of SD2 and MgO was also prepared. A binary SD without MgO (SD2) was also prepared for comparison in microenvironmental pH (pH(M)) modulation. The faster MgO released, the less control of pH(M) and the less enhanced dissolution of TEL were in consequences. SD3 increased dissolution in SIF and water (about 67%). Interestingly, ternary SD1 showed almost complete dissolution in all three media but dissolution of PM was the lowest due to the fast release of MgO and poor modulation of pH(M). MgO did not change the drug crystallinity but did have a strong molecular interaction with the drug. Additionally, the SD3-bearing tablet quickly increased pH(M) but then gradually decreased due to faster release of MgO while the SD1-bearing tablet gradually increased pH(M) at all fractional dimensions of the tablet by the MgO slowly released. The pH(M) of PM-bearing tablets was not varied as a function of time. Thus, the MgO-bearing SD1 also minimized gastrointestinal tissue damage caused by the model drug.

  3. Statin, Calcium Channel Blocker and Beta Blocker Therapy May Decrease the Incidence of Tuberculosis Infection in Elderly Taiwanese Patients with Type 2 Diabetes

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    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.

  4. A different dihydropyridine calcium channel blocker in hypertensive patients who developed pedal edema on dihydropyridine calcium channel blocker therapy

    Directory of Open Access Journals (Sweden)

    Ayşe Yüksel

    2014-03-01

    Full Text Available Abstract Aim. Dihydropyridine calcium channel blockers (CCB are widely preferred for the treatment of hypertension for their efficacy, metabolic neutrality and low side effect profile. However pedal edema formation limits their usage. The aim of the present study is to evaluate the incidence of pedal edema formation with a different dihydropyridine CCB in hypertensive patients who developed pedal edema during a dihydropyridine CCB therapy. Method. Fifty-eight hypertensive patients (34 female, 24 male, mean age: 65.3±10.5 in whom pedal edema developed during treatment with a dihydropyridine CCB (amlodipine 10mg/day in 40 patients, amlodipine 5mg/day in 14 patients, nifedipine GITS 30mg/day in 4 patients were enrolled. CCB which caused pedal edema was withdrawn and a different CCB (felodipine or lacidipine were initiated after the resolution of the pedal edema. CCB therapy was continued as long as the patient tolerated pedal edema. Results. At the end of one year, 44 out of 58 patients (36 [81.8%] free of pedal edema, 8 [19.2%] with pedal edema continued CCB therapy. Eleven (37.9% patients in the felodipine group and 9 (31.0% patients in the lacidipine group developed pedal edema. In 7 patients in felodipine group and in 5 patients in the lacidipine group the study drug was withdrawn due to pedal edema. In two patients, study drug was withdrawn due to intractable headache (felodipine group or due to flushing (lacidipine group. Conclusion. A different group of dihydropyridine CCB be used as an alternative therapy for hypertension whenever pedal edema develops during treatment with a dihydropyridine CCB.

  5. β blockers and mortality after myocardial infarction in patients without heart failure: multicentre prospective cohort study

    Science.gov (United States)

    Riant, Elisabeth; Aissoui, Nadia; Soria, Angèle; Ducrocq, Gregory; Coste, Pierre; Cottin, Yves; Aupetit, Jean François; Bonnefoy, Eric; Blanchard, Didier; Cattan, Simon; Steg, Gabriel; Schiele, François; Ferrières, Jean; Juillière, Yves; Simon, Tabassome; Danchin, Nicolas

    2016-01-01

    Objective To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction. Design Multicentre prospective cohort study. Setting Nationwide French registry of Acute ST- and non-ST-elevation Myocardial Infarction (FAST-MI) (at 223 centres) at the end of 2005. Participants 2679 consecutive patients with acute myocardial infarction and without heart failure or left ventricular dysfunction. Main outcome measures Mortality was assessed at 30 days in relation to early use of β blockers (≤48 hours of admission), at one year in relation to discharge prescription, and at five years in relation to one year use. Results β blockers were used early in 77% (2050/2679) of patients, were prescribed at discharge in 80% (1783/2217), and were still being used in 89% (1230/1383) of those alive at one year. Thirty day mortality was lower in patients taking early β blockers (adjusted hazard ratio 0.46, 95% confidence interval 0.26 to 0.82), whereas the hazard ratio for one year mortality associated with β blockers at discharge was 0.77 (0.46 to 1.30). Persistence of β blockers at one year was not associated with lower five year mortality (hazard ratio 1.19, 0.65 to 2.18). In contrast, five year mortality was lower in patients continuing statins at one year (hazard ratio 0.42, 0.25 to 0.72) compared with those discontinuing statins. Propensity score and sensitivity analyses showed consistent results. Conclusions Early β blocker use was associated with reduced 30 day mortality in patients with acute myocardial infarction, and discontinuation of β blockers at one year was not associated with higher five year mortality. These findings question the utility of prolonged β blocker treatment after acute myocardial infarction in patients without heart failure or left ventricular dysfunction. Trial registration Clinical trials NCT00673036. PMID:27650822

  6. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

    OpenAIRE

    Ivanov, Vadim; Ivanova, Svetlana; KALINOVSKY, TATIANA; NIEDZWIECKI, ALEKSANDRA; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition...

  7. 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

  8. Ischaemic heart disease: how well are the risk profiles modulated by current beta blockers?

    Science.gov (United States)

    Leren, P

    1993-01-01

    In acute myocardial infarction, intravenous beta blocker therapy has been tested in about 30 controlled, randomized trials. Of these, the ISIS-1 using atenolol and the MIAMI trial using metoprolol are the most important. In a total of 26,437 patients, total deaths were reduced by 62 during day 1 and by 64 during the first week, i.e. 97% of the lives were saved during the first day of beta blocker treatment. In post-myocardial infarction, oral beta blocker maintenance treatment has been used in about 35,000 survivors in placebo-controlled trials. Of these, the timolol, metoprolol and propranolol (BHAT) trials are the most important. In the timolol trial lasting for 33 months, total death, total cardiac death and re-infarction rate were significantly reduced. In the metoprolol study lasting for 3 months, total and cardiac mortality were reduced, and in the BHAT study lasting for 25 months fatal and non-fatal re-infarction combined was significantly reduced. Primary prevention of coronary heart disease has been the intention in hypertension trials. Despite the fact that beta blockers are potent agents against elevated blood pressure, a well-established coronary risk factor, no controlled trial with a placebo or untreated control group has shown a definite preventive effect on coronary heart disease. The reason for this apparent paradox is not known, but many speculations have been aired that the lack of effect might be due to adverse metabolic effects of most beta blockers.

  9. USE OF BETA-BLOCKERS IN THE PERIOPERATIVE PERIOD: HOW STRONG ARE THE EVIDENCES?

    Directory of Open Access Journals (Sweden)

    V. V. Samoylenko

    2013-01-01

    Full Text Available Optimization of the pharmacotherapy in preoperative period is the cornerstone of the concept of risk modification of cardiovascular complications in the perioperative period. Therefore, special attention has recently been focused on the use of beta-blockers in the postoperative period. Nowadays convincing evidence base for the use of this class of drugs in the perioperative period that was the basis for the development of clinical guidelines is accumulated. Moreover, results of large randomized trials of beta-blockers are controversial. This has resulted in significant differences in the classes of recommendations and levels of evidence.Analysis of the results of basic researches and the provisions of recommendations of the international and national professional medical societies on the use of beta-blockers in patients with cardiovascular disease to reduce the risk of cardiac complications in the perioperative period for planned extracardiac surgical procedures is presented.

  10. Roxatidine, an H(2) receptor blocker, is an estrogenic compound--experimental evidence.

    Science.gov (United States)

    Agrawal, Shyam Sundar; Alvin Jose, Manonmani

    2010-08-01

    Roxatidine is an H(2) receptor blocker frequently used in the treatment of peptic ulcers. H(2) receptor blockers are reported to show antifertility activity. To examine the mechanism of antifertility, estrogenic and antiestrogenic activity was studied using an in vitro rat and rabbit uterine receptor binding assay and in vivo using the uterotrophic assay in immature Wistar rats. The results revealed that roxatidine showed mild receptor binding affinity to both rat and rabbit uterine receptors when compared to estradiol. Interstingly, in vivo roxatidine increases the wet uterine weight of immature Wistar rats significantly (Proxatidine treated group was somewhat similar to that of the estradiol treated group. Histopathological results and the structure of the roxatidine support that H(2) receptor blocker roxatidine is an estrogenic compound.

  11. USE OF BETA-BLOCKERS IN THE PERIOPERATIVE PERIOD: HOW STRONG ARE THE EVIDENCES?

    Directory of Open Access Journals (Sweden)

    V. V. Samoylenko

    2015-09-01

    Full Text Available Optimization of the pharmacotherapy in preoperative period is the cornerstone of the concept of risk modification of cardiovascular complications in the perioperative period. Therefore, special attention has recently been focused on the use of beta-blockers in the postoperative period. Nowadays convincing evidence base for the use of this class of drugs in the perioperative period that was the basis for the development of clinical guidelines is accumulated. Moreover, results of large randomized trials of beta-blockers are controversial. This has resulted in significant differences in the classes of recommendations and levels of evidence.Analysis of the results of basic researches and the provisions of recommendations of the international and national professional medical societies on the use of beta-blockers in patients with cardiovascular disease to reduce the risk of cardiac complications in the perioperative period for planned extracardiac surgical procedures is presented.

  12. Unambiguous observation of blocked states reveals altered, blocker-induced, cardiac ryanodine receptor gating

    Science.gov (United States)

    Mukherjee, Saptarshi; Thomas, N. Lowri; Williams, Alan J.

    2016-01-01

    The flow of ions through membrane channels is precisely regulated by gates. The architecture and function of these elements have been studied extensively, shedding light on the mechanisms underlying gating. Recent investigations have focused on ion occupancy of the channel’s selectivity filter and its ability to alter gating, with most studies involving prokaryotic K+ channels. Some studies used large quaternary ammonium blocker molecules to examine the effects of altered ionic flux on gating. However, the absence of blocking events that are visibly distinct from closing events in K+ channels makes unambiguous interpretation of data from single channel recordings difficult. In this study, the large K+ conductance of the RyR2 channel permits direct observation of blocking events as distinct subconductance states and for the first time demonstrates the differential effects of blocker molecules on channel gating. This experimental platform provides valuable insights into mechanisms of blocker-induced modulation of ion channel gating. PMID:27703263

  13. Use of statins and beta-blockers after acute myocardial infarction according to income and education

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Nørgaard; Gislason, Gunnar H; Rasmussen, Søren

    2007-01-01

    OBJECTIVE: To study the initiation of and long-term refill persistency with statins and beta-blockers after acute myocardial infarction (AMI) according to income and education. DESIGN AND SETTING: Linkage of individuals through national registers of hospitalisations, drug dispensation, income...... and education. PARTICIPANTS: 30 078 patients aged 30-74 years surviving first hospitalisation for AMI in Denmark between 1995 and 2001. MAIN OUTCOME MEASURES: Initiation of statin or beta-blocker treatment (out-patient claim of prescriptions within 6 months of discharge) and refill persistency (first break.......66-0.82) and medium (HR 0.82; 95% CI 0.74-0.92) income compared with low income, whereas there was a trend in the opposite direction concerning a break in beta-blocker treatment. There was no gradient in re-initiation of treatment. CONCLUSION: Patients with low compared with high income less frequently initiated...

  14. 以介孔硅为基质的固体分散体片剂的制备与性质考察%Preparations and properties of the tablets formed with telmisartan and mesoporous silica

    Institute of Scientific and Technical Information of China (English)

    陈美洁; 张彦卓; 韩旭; 李文静; 姜同英

    2013-01-01

    Objective To prepare the tablets containing telmisartan and mesoporous silica solid disperse system and investigate its stability. Methods Based on the screening formulation, the tablets were produced with direct compression method. XRD and DSC were used for the identification of the crystal transformation, together with HPLC methods to quantify the drug. Results Telmisartan and mesoporous silica solid disperse system 66 g,crosslinked polyvinylpyrrolidone 30 g,microcrystalline cellulose 50 g, mannitol 50 g and magnesium stearate 4 g were mixed and directly compressed to produce 1 000 tablets, content uniformity and dissolution met the requirement, and stability was well and telmisartan in tablets maintained amorphous state during 12 months storage. Conclusions For poorly soluble crystalline drugs,short mesoporous pore channels of MSN self-made can be used to prepare the amorphous state solid disperse system, and the drug in its subsequent preparation can exist as amorphous state at least 12 months.%目的 将替米沙坦与介孔硅制备成片剂,并考察片剂的稳定性.方法 在处方筛选的基础上,采用粉末直接压片法压制替米沙坦-介孔硅片剂;采用高效液相色谱法测定药物含量;采用示差扫描量热、X-射线衍射和溶出法考察制剂的晶型稳定性.结果 替米沙坦-介孔硅分散体66 g、交联聚乙烯吡咯烷酮30 g、微晶纤维素50 g、甘露醇50 g、硬脂酸镁4 g,混合均匀,压制成1 000片,含量均匀度和溶出度符合要求,在12个月内替米沙坦稳定性良好,且一直以无定型状态存在.结论 利用自制介孔硅制备固体分散体,介孔硅的孔道使难溶性药物长期以无定型状态存在,故制剂稳定性良好.

  15. Effects of beta-blockers on heart failure with preserved ejection fraction: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Feng Liu

    Full Text Available BACKGROUND: Effects of beta-blockers on the prognosis of the heart failure patients with preserved ejection fraction (HFpEF remain controversial. The aim of this meta-analysis was to determine the impact of beta-blockers on mortality and hospitalization in the patients with HFpEF. METHODS: A search of MEDLINE, EMBASE, and the Cochrane Library databases from 2005 to June 2013 was conducted. Clinical studies reporting outcomes of mortality and/or hospitalization for patients with HFpEF (EF ≥ 40%, being assigned to beta-blockers treatment and non-beta-blockers control group were included. RESULTS: A total of 12 clinical studies (2 randomized controlled trials and 10 observational studies involving 21,206 HFpEF patients were included for this meta-analysis. The pooled analysis demonstrated that beta-blocker exposure was associated with a 9% reduction in relative risk for all-cause mortality in patients with HFpEF (95% CI: 0.87 - 0.95; P < 0.001. Whereas, the all-cause hospitalization, HF hospitalization and composite outcomes (mortality and hospitalization were not affected by this treatment (P=0.26, P=0.97, and P=0.88 respectively. CONCLUSIONS: The beta-blockers treatment for the patients with HFpEF was associated with a lower risk of all-cause mortality, but not with a lower risk of hospitalization. These finding were mainly obtained from observational studies, and further investigations are needed to make an assertion.

  16. Heart rate and use of beta-blockers in stable outpatients with coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Ph Gabriel Steg

    Full Text Available BACKGROUND: Heart rate (HR is an emerging risk factor in coronary artery disease (CAD. However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR. METHODS AND FINDINGS: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of >50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle East, and Asia/Pacific were enrolled between November 2009 and July 2010. Most of the 33,177 patients included in this analysis were men (77.5%. Mean (SD age was 64.2 (10.5 years, HR by pulse was 68.3 (10.6 bpm, and by electrocardiogram was 67.2 (11.4 bpm. Overall, 44.0% had HR ≥ 70 bpm. Beta-blockers were used in 75.1% of patients and another 14.4% had intolerance or contraindications to beta-blocker therapy. Among 24,910 patients on beta-blockers, 41.1% had HR ≥ 70 bpm. HR ≥ 70 bpm was independently associated with higher prevalence and severity of angina, more frequent evidence of myocardial ischemia, and lack of use of HR-lowering agents. CONCLUSIONS: Despite a high rate of use of beta-blockers, stable CAD patients often have resting HR ≥ 70 bpm, which was associated with an overall worse health status, more frequent angina and ischemia. Further HR lowering is possible in many patients with CAD. Whether it will improve symptoms and outcomes is being tested.

  17. Transport of beta-blockers and calcium antagonists by diffusion in cat myocardium

    DEFF Research Database (Denmark)

    Haunsø, Stig; Sejrsen, Per; Svendsen, Jesper Hastrup

    1991-01-01

    Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion. In anesthet......Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion...

  18. Blockers for non-crossing spanning trees in complete geometric graphs

    CERN Document Server

    Keller, Chaya; Rivera-Campo, Eduardo; Urrutia-Galicia, Virginia

    2012-01-01

    In this paper we present a complete characterization of the smallest sets that block all the simple spanning trees (SSTs) in a complete geometric graph. We also show that if a subgraph is a blocker for all SSTs of diameter at most 4, then it must block all simple spanning subgraphs, and in particular, all SSTs. For convex geometric graphs, we obtain an even stronger result: being a blocker for all SSTs of diameter at most 3 is already sufficient for blocking all simple spanning subgraphs.

  19. Alpha 1-blockers vs 5 alpha-reductase inhibitors in benign prostatic hyperplasia. A comparative review

    DEFF Research Database (Denmark)

    Andersen, J T

    1995-01-01

    During recent years, pharmacological treatment of symptomatic benign prostatic hyperplasia (BPH) has become the primary treatment choice for an increasing number of patients. The 2 principal drug classes employed are alpha 1-blockers and 5 alpha-reductase inhibitors. Current information from...... of patients who will respond well to alpha 1-blockers have yet to be identified, and data concerning the long term effects of these drugs are not yet available. 5 alpha-Reductase inhibitors have a slow onset of effect, but treatment leads to improvement in symptoms, reduction of the size of the prostate gland...... or unwilling to undergo surgical resection of the prostate will benefit from such therapy....

  20. PRESCRIBING PATTERN OF ANTIHYPERTENSIVES IN INDIVIDUALS WITH HYPERTENSION ALONE AND WITH COEXISTING DIABETES MELLITUS – A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    J. Keerthi Sagar*, S. Narendranath, H.S. Somashekar, S.R. Reshma, Susheela Somappa Halemani and Prabhakar Adake

    2012-06-01

    Full Text Available Objective: Analysis of prescribing pattern of antihypertensives in patients with hypertension alone and with coexisting diabetes mellitus. Materials and Methods: A cross sectional study was conducted in an outpatient and inpatient department of general medicine at JJM Medical College hospital for a period of 3 months (July 2011 to September 2011. Prescriptions of the patients were collected and relevant data was entered in the preformed proforma and analyzed.Results: A total of 210 prescriptions were analyzed using chi square test. Out of which 126 prescriptions were of patients with hypertension alone which contain calcium channel blockers (30%, beta blockers (26%, angiotensin receptor blockers (15%, angiotensin converting enzyme inhibitors (4% and fixed dose combinations of angiotensin receptor blockers with hydrochlorothiazide (11% and combination of amlodipine with hydro-chlorothiazide (2.5%.84 Prescriptions of hypertension with coexisting diabetes mellitus had calcium channel blockers (24%, angiotensin converting enzyme inhibitors (19%, angiotensin receptor blockers (13%, beta blockers (13%, and fixed dose combinations of angiotensin receptor blockers with hydrochlorothiazide (18% and combination of amlodipine with hydrochlorothiazide (6%.[χ2=17.01, p=o.oo4] Conclusion- The present study shows that angiotensin converting enzyme inhibitors because of its beneficial effects which are well known are more commonly prescribed drugs in individuals with hypertension with coexisting diabetes mellitus. Calcium channel blockers and newly introduced angiotensin receptor blockers alone or in combination with hydrochlorothiazide are preferred drugs in both the study groups. Beta blockers are less preferred in patients of hypertension with coexisting diabetes mellitus for obvious reasons.

  1. 替米沙坦对小鼠巨噬细胞 M1/M2亚型极化的影响%Effect of Telmisartan on mice macrophage M1/M2 polarization

    Institute of Scientific and Technical Information of China (English)

    邢亦明; 胡泽平; 王邦宁; 周青; 汪渊

    2016-01-01

    Objective To investigate the effect of Telmisartan on the M1 /M2 polarization of mice macrophage . Methods Mice macrophage was induced to M1 /M2 polarization by LPS +IFN-γand IL-4 respectively, and tested by immunofluorescence.Meanwhile cells were treated with 0.1,1,10 μmol /L Telmisartan,blank control group and vehicle control group were established at the same time .The biomarkers iNOS and Arg Ⅰ were tested by Western blot, and the cytokines IL-6 and IL-10 were tested by ELISA assay.Results The biomarker iNOS and IL-6,secre-ted by M1 macrophage, were apparently increased in the macrophages induced by LPS +IFN-γ.However, after be-ing treated with Telmisartan,the expressions of iNOS and IL-6 were obviously decreased(P <0.05), as the concen-tration higher the expression lower .While, the expression of Arg I and IL-10, which represented the M2 macro-phage, increased ( P <0.05).Conclusion Telmisartan can inhibit the M1 polarization of mice macrophage RAW264.7 induced by LPS and IFN-γand transform M1 macrophage polarization to M2 macrophage polarization.%目的探讨替米沙坦对小鼠巨噬细胞 M1/M2亚型极化的影响。方法分别用脂多糖(LPS)联合干扰素-γ(IFN-γ)和白介素-4(IL-4)诱导小鼠巨噬细胞 M1/M2型极化,用免疫荧光法检测极化结果。在 M1型巨噬细胞中分别加入0.1、1、10μmol/L 替米沙坦,同时设立空白对照组及溶剂对照组,Western blot 法检测各组巨噬细胞亚型标志物诱导性一氧化氮合酶(iNOS)和精氨酸酶Ⅰ(Arg Ⅰ)的表达情况, ELISA 法检测各组培养液上清中 IL-6、IL-10表达情况。结果在 LPS +IFN-γ诱导的小鼠巨噬细胞中 M1型巨噬细胞标志物 iNOS、IL-6的表达水平明显升高,替米沙坦干预后,各干预组 M1型巨噬细胞标志物 iNOS、IL-6的表达水平下降(P <0.05),随着替米沙坦浓度的增加而降低,而代表 M2型巨噬细胞标志物的 Arg

  2. Brain death provokes very acute alteration in myocardial morphology detected by echocardiography: preventive effect of beta-blockers.

    Science.gov (United States)

    Ferrera, René; Hadour, Guylaine; Tamion, Fabienne; Henry, Jean-Paul; Mulder, Paul; Richard, Vincent; Thuillez, Christian; Ovize, Michel; Derumeaux, Geneviève

    2011-03-01

    Our objective was to evaluate immediate acute changes in myocardial function during the autonomic storm of brain death (BD). Wistar rats were divided into four groups (n = 8/group): controls without any treatment, β-blocker (Esmolol®, 10 mg/kg), calcium channel blocker (Diltiazem®, 10 mg/kg), or alpha-blocker (Prazosin®, 0.3 mg/kg). Treatments were administered intravenously 5 min before BD induction. Echocardiography (ATL-5000, 8 MHz) was performed to measure left ventricular (LV) dimensions and fractional shortening at baseline, during BD induction and 5 min and 15 min after BD. In controls, BD was immediately associated with an increase in wall thickness and a decrease in LV cavity dimension. This myocardial wall hypertrophy was completely prevented by β-blockers, but not with calcium- and alpha-blockers. Extensive myocardial interstitial edema was found in all groups, except in the β-blocker group. Myocardial wall hypertrophy was also prevented during a longer follow-up of 180 min after BD in β-blocker group as opposed to controls. In conclusion, BD is associated with an immediate and severe myocardial damage related to an important interstitial edema which is prevented by β-blockers.

  3. Evaluation of risk of falls and orthostatic hypotension in older, long-term topical beta-blocker users

    NARCIS (Netherlands)

    W.D. Ramdas (Wishal); N. van der Velde (Nathalie); T.J.M. van der Cammen (Tischa); R.C.W. Wolfs (Roger)

    2009-01-01

    textabstractBackground: Falls are a serious problem in the elderly, and have recently been described as cardiovascular-mediated side effects of beta-blocker eye drops. Therefore, we investigated the possible association between the long-term use of beta-blockers, prostaglandins and their combination

  4. Synthesis and Effects of Novel Dihydropyridines as Dual Calcium Channel Blocker and Angiotensin Antagonist on Isolated Rat Aorta

    Directory of Open Access Journals (Sweden)

    Farzin Hadizadeh

    2010-01-01

    Full Text Available Four novel losartan analogues 5a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of 5a and 5b on angiotensin receptors (AT1 and L-type calcium channels were investigated on isolated rat aorta. Materials and MethodsAortic rings were pre-contracted with 1 µM Angiotensin II or 80 mM KCl and relaxant effects of losartan, nifedipine, 5a and 5b were evaluated by cumulative addition of these drugs to the bath solution.ResultsThe results showed that compounds 5a and 5b have both L-type calcium channel and AT1 receptor blocking activity. Their effects on AT1 receptors are 1000 and 100,000 times more than losartan respectively. The activity of compound 5b on L-type calcium channel is significantly less than nifedipine but compound 5a has comparable effect with nifedipine. ConclusionFinally we concluded that these two new Compounds can be potential candidates to be used as effective antihypertensive agents.

  5. Effect of beta-blocker therapy on functional status in patients with heart failure--a meta-analysis

    DEFF Research Database (Denmark)

    Abdulla, Jawdat; Køber, Lars; Christensen, Erik

    2005-01-01

    BACKGROUND: The results of randomised control trials (RCTs) evaluating the effect of beta-blockers on functional status in patients with chronic heart failure are conflicting. AIM: To perform a systematic review and meta-analysis of RCTs evaluating the effect of beta-blockers on New York Heart...... Association (NYHA) classification and exercise tolerance in chronic heart failure. METHODS AND RESULTS: We selected 28 RCTs evaluating beta-blocker versus placebo in addition to ACE inhibitor therapy. Combined results of 23 RCTs showed that beta-blockers improved NYHA class by at least one class with odds...... ratio (OR) 1.80 (1.33-2.43) pbeta-blockers had no significant effect...

  6. SAFETY AND EFFICACY OF BETA-BLOCKERS IN THE TREATMENT OF STABLE ANGINA-PECTORIS

    NARCIS (Netherlands)

    DEMUINCK, ED; LIE, KI

    1990-01-01

    In stable exercise-induced angina pectoris, beta-blockers exert their beneficial effects mainly through a reduction in heart rate, blood pressure, and contractility. Additional beneficial effects are an improvement in myocardial oxygen supply through a redistribution of coronary flow, a lengthening

  7. Topical ophthalmic beta blockers may cause release of histamine through cytotoxic effects of inflammatory cells

    NARCIS (Netherlands)

    Beek, van L.M.; Mulder, M.; Haeringen, van N.J.; Kijlstra, A.

    2000-01-01

    Aim - To evaluate the effects of β blockers used in ophthalmology on the release of histamine from mixed cell preparations containing human leucocytes and basophils. Methods - A mixed leucocyte and basophil preparation was obtained from venous blood of healthy non-atopic volunteers. Cell preparation

  8. Bed blockers: A study on the elderly patients in a teaching hospital in India

    Directory of Open Access Journals (Sweden)

    Praveen Kumar N

    2010-07-01

    Full Text Available A cross-sectional study of in-patients over the age of 60 years was conducted at district McGann Hospital, Shimoga on patients who were classified as bed blockers. Level of dependency and cognitive function of these patients were assessed using Barthel scale and Abbreviated mental test (AMT respectively. Median age of the study population was 67 years; majority of them were men. Most of them were admitted in the medical ward and the median time to be labeled as bed blocker was 32 days. These bed blockers were a weak group of patients with an average 3.1 pathology per case. Majority of them suffered from neurological disorders and cardiovascular disease. High level of dependence was noted with a mean Barthel score of 29.68 (Range 0 -100. Low levels of cognitive function was also noted among these patients with a mean AMT of 4.76 (Range 0 -10.These findings demonstrate that the bed blockers in McGann hospital suffer not only from genuine health problems but also have a high dependency level in activities of daily living which hamper their discharge to the community. Community based rehabilitation using an intersectoral approach may help at least the less dependent to return home.

  9. Calcium channel blockers and cancer : A risk analysis using the UK Clinical Practice Research Datalink (CPRD)

    NARCIS (Netherlands)

    Grimaldi-Bensouda, Lamiae; Klungel, Olaf; Kurz, Xavier; De Groot, Mark C H; Afonso, Ana S Maciel; De Bruin, Marie L.; Reynolds, Robert; Rossignol, Michel

    2016-01-01

    OBJECTIVE: The evidence of an association between calcium channel blockers (CCBs) and cancer is conflicting. The objective of the present study was to evaluate the risk of cancer (all, breast, prostate and colon cancers) in association with exposure to CCB. METHODS: This is a population-based cohort

  10. Inhibitory effects of calcium channel blockers on thyroid hormone uptake in neonatal rat cardiomyocytes

    NARCIS (Netherlands)

    F.A. Verhoeven; E.P.C.M. Moerings (Ellis); J.M.J. Lamers (Jos); G. Hennemann; T.J. Visser (Theo); M.E. Everts (Maria)

    2001-01-01

    textabstractThe effects of the Ca2+ channel blockers verapamil, nifedipine, and diltiazem on triiodothyronine (T3) and thyroxine (T4) uptake were tested in cultured cardiomyocytes from 2-day-old rats. Experiments were performed at 37 degrees C in medium with 0.5% BSA for [125I]T3 (

  11. Incidence of ocular side effects of topical beta blockers in the Netherlands

    NARCIS (Netherlands)

    Beek, van L.M.; Keizer, de R.J.W.; Polak, B.C.P.; Elzenaar, P.R.; Haeringen, van N.J.; Kijlstra, A.

    2000-01-01

    Background - Several ocular side effects including uveitis, have been reported following topical β blocker treatment for glaucoma and ocular hypertension. The incidence of these side effects was investigated in the Netherlands. Methods - A prospective observational design was used whereby monthly qu

  12. 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...

  13. Renoprotective effect of combining angiotensin Ⅱ receptor blockers and statins in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    GAO Ping; JIA Ru-han; YANG Ding-ping; LIU Hong-yan; SONG En-feng; CHU Gui-li; DING Guo-hua

    2005-01-01

    @@ Recent studies suggest that treatment with angiotensin Ⅱ type 1 (AT1) receptor blockers and lipid lowering agents, namely the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins may have beneficial effects on renal function independent of lowering actions on blood pressure and cholesterol.

  14. Chronic beta-blocker treatment in patients with advanced heart failure - Effects on neurohormones

    NARCIS (Netherlands)

    Teisman, ACH; van Veldhuisen, DJ; Boomsma, F; de Kam, PJ; Pinto, YM; de Zeeuw, D; van Gilst, WH

    2000-01-01

    Background: To date, the use of beta-blockers in treating patients with chronic heart failure gains support, this since several large clinical trials reported reduced mortality after chronic beta-blockade. Part of these beneficial effects may result from inhibition of deleterious neurohormone activa

  15. INHIBITION OF KIDNEY DISORDERS IN CARDIOVASCULAR DISEASES: THE ROLE OF ANGIOTENSIN II RECEPTOR BLOCKERS

    Directory of Open Access Journals (Sweden)

    V. V. Fomin

    2008-01-01

    Full Text Available Mechanisms of renal disorders in cardiovascular diseases are presented. The main of these mechanisms is an endothelium dysfunction. It is related with some factors: arterial hypertension, insulin resistance syndrome, diabetes type 2, dyslipidemia, obesity. Approaches to prevention of kidney disorder and cardiovascular complications are discussed with focus on usage of angiotensin II receptor blockers.

  16. The use of guideline recommended beta-blocker therapy in primary prevention implantable cardioverter defibrillator patients

    DEFF Research Database (Denmark)

    Ruwald, Anne-Christine; Gislason, Gunnar Hilmar; Vinther, Michael

    2017-01-01

    Aims: We aimed to examine the use of guideline recommended beta-blocker therapy prior to and after primary prevention implantable cardioverter defibrillator (ICD) implantation in a 'real-life' setting. Methods and results: From the Danish Pacemaker and ICD Registry we identified all 1st-time prim......Aims: We aimed to examine the use of guideline recommended beta-blocker therapy prior to and after primary prevention implantable cardioverter defibrillator (ICD) implantation in a 'real-life' setting. Methods and results: From the Danish Pacemaker and ICD Registry we identified all 1st......-time primary prevention ICD and cardiac resynchronization therapy defibrillator (CRT-D) implantations in Denmark from 2007-12 (n = 2935). Use of beta-blocker, type and dose was acquired through the Danish Prescription Registry. According to guideline recommendations, we defined target daily doses as ≥50 mg...... carvedilol and ≥200 mg metoprolol. Prior to implantation 2427 of 2935 (83%) patients received beta-blocker therapy, with 2166 patients (89%) having initiated treatment 3 months or more prior to implantation. The majority of patients was prescribed carvedilol (52%) or metoprolol (41%). Patients on carvedilol...

  17. Treatment with beta-blockers in nurse-led heart failure clinics

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Schou, Morten; Videbaek, Lars

    2007-01-01

    BACKGROUND: Beta-blockers (BBs) are a cornerstone in the treatment of chronic heart failure (HF), but several surveys have documented that many patients are not offered treatment or are not titrated to target doses. In part to address this problem, specialized, nurse-led HF clinics have been...

  18. Playing with Performance: The Use and Abuse of Beta-Blockers in the Performing Arts

    Science.gov (United States)

    Patston, Tim; Loughlan, Terence

    2014-01-01

    This article discusses the use of beta-blockers by performing artists, the reasons why they are taken, and the potential associated risks. We argue that there are high levels of usage within sectors of the professional performing arts community and that there may be high levels of risk in using these medications, particularly without medical…

  19. [Influence of rifampicin on antihypertensive effects of dihydropiridine calcium-channel blockers in four elderly patients].

    Science.gov (United States)

    Yoshimoto, H; Takahashi, M; Saima, S

    1996-09-01

    Rifamicin, an antituberculosis agent, is one of the most potent inducers of hepatic drug-oxidation enzymes. Rifampicin can reduce the efficacy of several therapeutically important drugs (including verapamil and diltiazem) by accelerating systemic elimination or by increasing hepatic first-pass metabolism. Because dihydropyridine calcium-channel blockers are mainly metabolized by the liver, rifampicin may also increase the extraction of these drugs and thereby reduce their antihypertensive effects. Here we report four possible cases of interaction between rifampicin and dihydropiridine calcium-channel blockers. Rifampicin was given to treat tuberculosis in four elderly hypertensive patients whose blood pressure was well-controlled by one or more dihydropiridine calcium-channel blockers (nisoldipine, nifedipine, or barnidipine and manidipine), shortly after the start of antituberculosis therapy, their blood pressures rose. Either much greater doses of dihydropyridines or additional antihypertensive agents had to be given to keep blood pressure under control. After withdrawal of rifampicin, blood pressure fell in all patients and the doses of the antihypertensive agents had to be reduced. These findings indicate that rifampicin may lessen the antihypertensive effects of dihydropiridine calcium-channel blockers.

  20. Non-selective β-blockers do not affect mortality in cirrhosis patients with ascites

    DEFF Research Database (Denmark)

    Bossen, Lars; Krag, Aleksander; Vilstrup, Hendrik

    2016-01-01

    The safety of non-selective β-blockers (NSBBs) in advanced cirrhosis has been questioned. We used data from three satavaptan trials to examine whether NSBBs increase mortality in cirrhosis patients with ascites. The trials were conducted in 2006-2008 and included 1198 cirrhosis patients with asci...

  1. Comparison of the antagonistic effects of different angiotensin II receptor blockers in human coronary arteries

    DEFF Research Database (Denmark)

    Pantev, Emil; Stenman, Emelie; Wackenfors, Angelica;

    2002-01-01

    BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor and a deleterious factor in cardiovascular pathophysiology. Ang II receptor blockers (ARBs) have recently been introduced into clinical practice for treatment of hypertension and congestive heart failure. AIMS: This study was underta...

  2. Calcium-channel blockers for the prevention of stroke: from scientific evidences to the clinical practice

    Directory of Open Access Journals (Sweden)

    S. Taddei

    2013-05-01

    Full Text Available AIM OF THE REVIEW The present review aims to analyze the role of calcium-channel blockers, and particularly newer molecules, as first-line therapy for cerebrovascular disease. BACKGROUND Stroke is the leading cause of disability in the general population. Among traditional cardiovascular risk factors, hypertension has a key role in the genesis of both hemorrhagic and ischemic stroke and a direct correlation exists between blood pressure values and the risk of stroke. Moreover, blood pressure reduction has been demonstrated to be the most important route to reduce stroke incidence and recurrence. However, the mere reduction of blood pressure values does not normalize the cardiovascular risk of the hypertensive patient. It is therefore necessary to use drug classes that beyond their blood pressure-lowering effect have also an additional effect in terms of organ protection. Among these, calcium-channel blockers have a crucial profile. Firstly, they are effective in inducing left ventricular hypertrophy regression, with a strength at least equal to that of ACE-inhibitors. Secondly, they have an antithrombotic and an endothelium-protecting effect, mediated by their antioxidant activity. Finally, calcium-channel blockers are the most powerful drugs in preventing vascular remodeling. For these reasons this drug class has probably the strongest antiatherosclerotic effect, and it is the first-choice treatment mainly for cerebrovascular disease. Among different available calcium-channel blockers, the newer ones seem to possess pharmacokinetic characteristics allowing a more homogeneous 24 hours coverage as compared to older molecules, and preliminary data seem to suggest a greater beneficial effect also on left ventricular hypertrophy and lower incidence of side effects. CONCLUSIONS Although blood pressure reduction is the main tool to reduce cerebrovascular risk in hypertensive patients, some drug classes, such as calciumchannel blockers, seem to provide

  3. Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator

    OpenAIRE

    Hoogwegt, Madelein; Kupper, Nina; Theuns, Dominic; Jordaens, Luc; Pedersen, Susanne

    2012-01-01

    textabstractBeta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD. Between 2003 a...

  4. Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator

    DEFF Research Database (Denmark)

    Hoogwegt, Madelein T; Kupper, Nina; Theuns, Dominic A M J

    2012-01-01

    Beta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress. We...... investigated the association between beta-blocker therapy, including type and dosage, and symptoms of anxiety and depression in a consecutive cohort of patients receiving an ICD....

  5. Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverter-defibrillator

    NARCIS (Netherlands)

    M.T. Hoogwegt (Madelein); N. Kupper (Nina); D.A.M.J. Theuns (Dominic); L.J.L.M. Jordaens (Luc); S.S. Pedersen (Susanne)

    2012-01-01

    textabstractBeta-blockers are frequently prescribed to implantable cardioverter-defibrillator (ICD) patients. Beta-blocker therapy has been proposed to induce emotional distress such as depression and anxiety, but a paucity of studies has examined the relationship between beta-blockers and distress.

  6. Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 4: Alpha blockers v calcium blockers to increase spontaneous passage of renal calculi.

    Science.gov (United States)

    Stewart, Alexander; Ferguson, Craig

    2013-02-01

    A short cut review was carried out to establish the administration of an alpha-1 receptor antagonist or a calcium channel blocker would facilitate the most rapid and successful expulsion of a stone from a patient with uncomplicated renal colic. 597 articles were found using the reported search, of which five trials were selected as providing the best evidence to answer this question. The authors, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that in a patient with an uncomplicated ureteric calculus tamsulosin is more effective than nifedipine in promoting speedy and successful expulsion of the stone.

  7. Lack of effect of beta-blocker on flat dose response to thiazide in hypertension: efficacy of low dose thiazide combined with beta-blocker.

    OpenAIRE

    1983-01-01

    Increasing the dose of a thiazide diuretic used alone in patients with essential hypertension has little further effect on blood pressure but increases the deleterious metabolic consequences of the diuretic. The effect of a beta-blocker on this flat dose response is not known. In two randomised crossover studies the effect of 12.5 mg, 25 mg, and 50 mg hydrochlorothiazide combined with 400 mg acebutolol was assessed. The mean fall in supine blood pressure was about 15% and was the same whateve...

  8. Effects of chloride channel blockers on hypotonicity-induced contractions of the rat trachea

    Science.gov (United States)

    Coelho, Roberta R; Souza, Emmanuel P; Soares, Pedro M G; Meireles, Ana Vaneska P; Santos, Geam C M; Scarparo, Henrique C; Assreuy, Ana Maria S; Criddle, David N

    2003-01-01

    We have investigated the inhibitory effects of blockers of volume-activated (Clvol) and calcium-activated (ClCa) chloride channels on hypotonic solution (HS)-induced contractions of rat trachea, comparing their effects with those of the voltage-dependent calcium channel (VDCC) blocker nifedpine. HS elicited large, stable contractions that were partially dependent on the cellular chloride gradient; a reduction to 41.45±7.71% of the control response was obtained when extracellular chloride was removed. In addition, HS-induced responses were reduced to 26.8±5.6% of the control by 1 μM nifedipine, and abolished under calcium-free conditions, indicating a substantial requirement for extracellular calcium entry, principally via VDCCs. The established Clvol blockers tamoxifen (⩽10 μM) and 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (1–100 μM), at concentrations previously reported to inhibit Clvol in smooth muscle, did not significantly inhibit HS-induced contractions. In contrast, the recognized ClCa blocker niflumic acid (NFA; 1–100 μM) produced a reversible, concentration-dependent inhibition of HS responses, with a reduction to 36.6±6.4% of control contractions at the highest concentration. The mixed Clvol and ClCa blocker, 5-nitro 2-(3-phenylpropylamine) benzoic acid (NPPB; 10–100 μM) also elicited concentration-related inhibition of HS-induced contractions, producing a decrease to 35.9±11.3% of the control at 100 μM. Our results show that HS induces reversible, chloride-dependent contractions of rat isolated trachea that were inhibited by NFA and NPPB, while exhibiting little sensitivity to recognized blockers of Clvol. The data support the possibility that opening of calcium-activated chloride channels under hypotonic conditions in respiratory smooth muscle may ultimately lead to VDCC-mediated calcium entry and contraction. PMID:14691057

  9. Characterization of in vivo and in vitro electrophysiological and antiarrhythmic effects of a novel IKACh blocker, NIP-151: a comparison with an IKr-blocker dofetilide.

    Science.gov (United States)

    Hashimoto, Norio; Yamashita, Toru; Tsuruzoe, Nobutomo

    2008-02-01

    We investigated the electrophysiological and antiarrhythmic effects of a novel antiarrhythmic agent, NIP-151, and compared these effects with those of an IKr-blocker dofetilide. NIP-151 potently inhibited acetylcholine-activated K current (IKACh) with an IC50, with 1.6 nM in HEK293 cells expressing the GIRK1/4 channel, but it had little effect on IKr (IC50 = 57.6 microM). NIP-151 dose-dependently terminated AF both in vagal nerve stimulation-induced AF (at 5 and 15 microg/kg per minute) and aconitine-induced AF (at 30 and 100 microg/kg) models. This compound significantly prolonged the atrial effective refractory period (ERP), but it had no significant effects on ventricular ERP. There were no significant changes on electrocardiographic variables with NIP-151 (up to 1,000 microg/kg per minute) administration. In contrast, dofetilide had little effect in either AF model, even though this compound potently prolonged atrial ERP. Dofetilide also significantly prolonged ventricular ERP and the QT interval in anesthetized dogs, which are related to proarrhythmic risk. In conclusion, a novel antiarrhythmic agent NIP-151, which potently blocked IKACh, was highly effective in the two types of canine AF models with an atrial-specific ERP-prolonging profile. Therefore, NIP-151 might be useful for the treatment of AF with lower risk of proarrhythmia, compared with IKr blockers.

  10. Facile diverted synthesis of pyrrolidinyl triazoles using organotrifluoroborate: discovery of potential mPTP blockers.

    Science.gov (United States)

    Jung, Sun hwa; Choi, Kihang; Pae, Ae Nim; Lee, Jae Kyun; Choo, Hyunah; Keum, Gyochang; Cho, Yong Seo; Min, Sun-Joon

    2014-12-21

    This article describes the rapid and diversified synthesis of pyrrolidinyl triazoles for the discovery of mitochondrial permeability transition pore (mPTP) blockers. The 1,3-dipolar cycloaddition of ethynyl trifluoroborate with azidopyrrolidine produced a key intermediate, triazolyl trifluoroborate 4, which subsequently underwent a Suzuki-Miyaura coupling reaction to afford a series of 1,4-disubstituted triazoles 2. Subsequent biological evaluation of these derivatives indicated 2ag and 2aj as the most potent mPTP blockers exhibiting excellent cytochrome P450 (CYP) stability when compared to the previously reported oxime analogue 1. The present work clearly demonstrates that a 1,2,3-triazole can be used as a stable oxime surrogate. Furthermore, it suggests that late-stage diversification through coupling reactions of organotrifluoroborates is suitable for the rapid discovery of biologically active molecules.

  11. The role of aldosterone receptor blocker therapy in hypertension and heart failure

    Directory of Open Access Journals (Sweden)

    Giuseppina Santese

    2015-09-01

    Full Text Available The aldosterone receptor blocker therapy as an “add-on” to hypotensive therapy is an excellent therapeutic strategy that has proved to be particularly effective in treating refractory hypertension, hypertension with organ damage and overweight hypertensive patients. Aldosterone receptor blockers are extremely useful in inhibiting hormonal activation linked with heart failure: they have cardioprotective effects not only during full-blown heart failure, but also in its early stages, and this effect can be observed even more frequently in heart failures with metabolic syndrome. The use of molecules such as canrenone with a favorable tolerability profile ensures a better tolerability ratio by providing benefits linked to fewer drug interactions, lower incidence of side effects and improved therapy adherence.

  12. Atrial fibrillation pharmacotherapy after hospital discharge between 1995 and 2004: a shift towards beta-blockers

    DEFF Research Database (Denmark)

    Hansen, Morten Lock; Gadsbøll, Niels; Gislason, Gunnar H;

    2008-01-01

    AIMS: To study evolvement in pharmacotherapy of atrial fibrillation from 1995 to 2004. METHODS AND RESULTS: All Danish patients were discharged following first-time atrial fibrillation and their pharmacotherapy was identified by individual-level-linkage of nationwide registers of hospitalization ...... and drug dispensing from pharmacies. A total of 108 791 patients survived 30 days after discharge and were included. In 1995-1996, 7.4% of the patients received beta-blockers, increasing to 44.3% in 2003-2004. The corresponding figures for amiodarone were 2.9 and 5.4%. In contrast, use...... has changed towards increased beta-blocker use with a coincident decrease in the use of other rate-limiting drugs and sotalol. Treatment with amiodarone or class 1C antiarrhythmics remained very low. Oral anticoagulant therapy increased considerably, but women and elderly were apparently undertreated....

  13. The gap junction blocker carbenoxolone enhances propofol and sevoflurane-induced loss of consciousness

    Institute of Scientific and Technical Information of China (English)

    Zhigang Liu; Yongfang Liu; Bo Zhao; Li Du; Zhongyuan Xia; Xiangdong Chen; Tao Luo

    2012-01-01

    General anesthetics induce loss of consciousness by inhibiting ascending arousal pathways, and they interfere with gap junction electrical coupling.The present study aimed to determine whether inhibition of gap junction-mediated signaling could influence general anesthetic-induced loss of consciousness.The general anesthetics sevoflurane and propofol were used.Intracerebroventricular administration of carbenoxolone, a gap junction blocker, significantly decreased the time to loss of the righting reflex (P < 0.05), but prolonged the time to recovery of the reflex (P < 0.05).Moreover, intracerebroventricular administration of carbenoxolone increased the sensitivity to sevoflurane, with a leftward shift of the loss of righting reflex dose-response curve, and decreased the 50% effective concentration of sevoflurane.These results suggest that the gap junction blocker carbenoxolone enhances propofol and sevoflurane-mediated general anesthesia.

  14. In Silico Predictions of hERG Channel Blockers in Drug Discovery

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Sørensen, Flemming Steen

    2011-01-01

    drugs with different therapeutic indications and recognized as hERG blockers were recently withdrawn due to the risk of QT prolongation, arrhythmia and Torsade de Pointes.In silico techniques can provide a priori knowledge of hERG blockers, thus reducing the costs associated with screening assays......The risk for cardiotoxic side effects represents a major problem in clinical studies of drug candidates and regulatory agencies have explicitly recommended that all new drug candidates should be tested for blockage of the human Ether-a-go-go Related-Gene (hERG) potassium channel. Indeed, several....... Significant progress has been made in structure-based and ligand-based drug design and a number of models have been developed to predict hERG blockage.Although approaches such as homology modeling in combination with docking and molecular dynamics bring us closer to understand the drug-channel interactions...

  15. In silico predictions of hERG channel blockers in drug discovery

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Jørgensen, Flemming Steen

    2011-01-01

    drugs with different therapeutic indications and recognized as hERG blockers were recently withdrawn due to the risk of QT prolongation, arrhythmia and Torsade de Pointes. In silico techniques can provide a priori knowledge of hERG blockers, thus reducing the costs associated with screening assays......The risk for cardiotoxic side effects represents a major problem in clinical studies of drug candidates and regulatory agencies have explicitly recommended that all new drug candidates should be tested for blockage of the human Ether-a-go-go Related-Gene (hERG) potassium channel. Indeed, several....... Significant progress has been made in structure-based and ligand-based drug design and a number of models have been developed to predict hERG blockage. Although approaches such as homology modeling in combination with docking and molecular dynamics bring us closer to understand the drug-channel interactions...

  16. Applying Theoretical Approach for Predicting the Selective Calcium Channel Blockers Pharmacological Parameter by Biopartitioning Micellar Chromatography

    Institute of Scientific and Technical Information of China (English)

    WANG Su-Min; YANG Geng-Liang; LI Zhi-Wei; LIU Hai-Yan; GUO Hui-Juan

    2006-01-01

    The usefulness of biopartitioning micellar chromatography (BMC) for predicting oral drug acute toxicity and apparent bioavailability was demonstrated. A logarithmic model (an LD50 model) and the second order polynomial models (apparent bioavailability model) have been obtained using the retention data of the selective calcium channel blockers to predict pharmacological properties of compounds. The use of BMC is simple, reproducible and can provide key information about the acute toxicity and transport properties of new compounds during the drug discovery process.

  17. Practical guidelines for treatment with beta-blockers and nitrates in patients with acute myocardial infarction

    OpenAIRE

    Simoons, Maarten; Serruys, Patrick; Fioretti, Paolo; Brand, Marcel; Hugenholtz, Paul

    1983-01-01

    textabstractTreatment of a patient with myocardial infarction might include opiates and sedatives to reduce pain and anxiety, heparin, antiarrhythmic drugs, diuretics which aim at improvement of myocardial function and drugs which might reduce the ischemic area at risk and thus mortality such as beta-blockers, vasodilators and possibly calcium antagonists. Obviously a selection of these and other therapeutic agents should be made for each individual patient. Guidelines for such a selection ar...

  18. I(Kur)/Kv1.5 channel blockers for the treatment of atrial fibrillation.

    Science.gov (United States)

    Tamargo, Juan; Caballero, Ricardo; Gómez, Ricardo; Delpón, Eva

    2009-04-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia. Anti-arrhythmic drugs remain the mainstay of therapy, but the available class I and III anti-arrhythmic drugs are only moderately effective in long-term restoring/maintaining sinus rhythm (SR) and can produce potentially fatal ventricular pro-arrhythmia. In an attempt to identify safer and more effective anti-arrhythmic drugs, drug discovery efforts have focused on 'atrial selective drugs' that target cardiac ion channel(s) that are exclusively or predominantly expressed in the atria. The ultra-rapid activating delayed rectifier K(+) current (I(Kur)), carried by Kv1.5 channels, is a major repolarizing current in human atria, but seems to play no role in the ventricle. This finding offers the possibility of developing selective I(Kur) blockers to restore and maintain SR without a risk of ventricular pro-arrhythmia. Several I(Kur) blockers are now being developed but clinical data are still limited, so the precise role of these agents in the treatment of AF remains to be defined. In this review we analyze the possible advantages and disadvantages of the developmental I(Kur) blockers as they represent the first step for the development of potential atrial selective drugs for a more effective and safer treatment and prevention of AF.

  19. [Central effects of five beta-adrenergic receptor blockers in healthy volunteers: a quantitative EEG study].

    Science.gov (United States)

    Sabot, C; Pechadre, J C; Beudin, P; Lauxerois, M; Trolese, J F; Kantelip, J P; Ducher, J L; Gibert, J

    1989-03-01

    The effects of five beta blockers on the central nervous system of healthy subjects was studied by computerized EEG analysis. All subjects underwent continuous recording with a Holter magnetic type recorder during the experimental period. For 10 consecutive days, five groups of subjects received alternately placebo and the beta blockers acebutolol 600 mg, carteolol 20 mg, metoprolol 200 mg, pindolol 30 mg and sotalol 320 mg. EEG recordings (C4/P4, P4/02 and C3/P3, P3/01) lasting 5 min were made between 8.30 and 9.30 a.m. Subjects were at rest with eyes closed and there was no vigilance control. The signal was recorded on a magnetic tape recorder and then processed by Nicolet MED 80 system. Comparisons of absolute and relative powers and of average frequencies were then made between the different sequences and groups. The possible correlations between the changes observed in the power spectrum and the clinical, pharmacological and pharmacokinetic specific properties of each beta blocker are discussed.

  20. Mortality and Reinfarction among Patients Using Different Beta-Blockers for Secondary Prevention after a Myocardial Infarction

    DEFF Research Database (Denmark)

    Andersen, Søren Skøtt; Hansen, Morten Lock; Gislason, Gunnar H

    2009-01-01

    Objectives: To study differences in the clinical efficacy of various brands of beta-blocker in secondary prevention after a myocardial infarction (MI). Methods: All patients hospitalized with a first MI between 1995 and 2002 who were still alive 30 days after discharge and had had at least one...... prescription for a beta-blocker filled were identified by individual-level linkage of nationwide registries of hospitalizations and drugs dispensed from pharmacies. A total of 32,259 MI patients were included in the study. Multivariable Cox proportional hazard models were used to analyze the risks of death...... and recurrent MI related to treatment with different beta-blockers. Results: The risks for death and recurrent MI were similar in patients using different beta-blockers, except that mortality from all causes among patients with a prescription for sotalol was higher. Subgroup analyses of high-risk patients...

  1. Telmisartan Tablets in Different Dissolution Medium Leaching Behavior Comparison%替米沙坦片在不同溶出介质中的溶出行为比较

    Institute of Scientific and Technical Information of China (English)

    蒋玲; 毕学苑; 葛畅; 梅丽; 刘玮

    2013-01-01

    Objective Compare the in-vitro dissolution of telmisartan tablets from dif erent manufacturers. Methods The dissolution of telmisartan tablets from A、B、C and D manufacturers was determined by UV, and similarity for dissolution was evaluated by f2 factor. Results Compared with Micardis made by Boehringer Ingelheim, the similarity factors of telmisartan tablets made by manufacturers B, C and D in distil ed water were 83.0、86.4、84.3、65.8 and 37.7, respectively. In the hydrochloric acid solution(pH1.2), the similarity factors were 70.4、70.0、75.7、64.7 and 37.3, respectively. In the phosphate buf er(pH6.8), the similarity factors were 69.8、66.3、65.7、59.2 and 41.9, respectively. Conclusion The dissolution characteristics of manufacturers B and C were similar to Boehringer Ingelheim, and the dissolution characteristic of manufacturer D was dif erent significantly.%目的对替米沙坦片的体外溶出行为进行比较。方法采用UV法分别测定A、B、C、D厂替米沙坦片在水、盐酸溶液(pH1.2)、磷酸盐缓冲液(pH6.8)为溶出介质的累积溶出度,使用FDA推荐的相似因子法对溶出度曲线进行相似性比较。结果以原研厂家勃林格殷格翰公司的替米沙坦片(美卡素)为参比制剂,以水为溶出介质B(3批)、C、D厂的相似因子分别为83.0、86.4、84.3、65.8、37.7;以盐酸溶液(pH1.2)为溶出介质的 B(3批)、C、D厂的相似因子分别为70.4、70.0、75.7、64.7、37.3;以磷酸盐缓冲液(pH6.8)为溶出介质的B(3批)、C、D厂的相似因子分别为69.8、66.3、65.7、59.2、41.9。结论 B厂3批替米沙坦片在水、盐酸溶液(pH1.2)、磷酸盐缓冲液(pH6.8)3种溶出介质的溶出行为均与参比制剂非常相似;C厂有一定的相似性;D厂则存在较大差异。

  2. Chronobiologically Explored Effects of Telmisartan#

    OpenAIRE

    2005-01-01

    Effects of Micardis (Telmisarian), alone or with low-dose aspirin, on blood pressure and other cardiovascular endpoints are examined in 20 patients with MESOR-hypertension in a crossover, double-blind, randomized study consisting of three Stages, each lasting 7 days: I-placebo, II-Micardis, and III-Micardis with low-dose aspirin. Treatment was administered each day at a different circadian stage, upon awakening, and 3, 6, 9, 12, 15 and 18 hr after awakening. During each stage, the following v...

  3. [Physiotherapy in correction of proatherogenic shifts in long-term administration of beta-blockers and thiazide diuretics].

    Science.gov (United States)

    Razumov, A N; Kniazeva, T A; Badtieva, V A

    2002-01-01

    A physiotherapeutic complex (laser therapy, dry carbon dioxide and iodine-bromine baths) addition to a course treatment with beta-blockers and thiazide diuretics produced positive changes in the levels of triglicerides, total cholesterol, beta- and alpha-cholesterol, lipid peroxidation in patients with proatherogenic shifts in the lipid spectrum and lipid peroxidation system secondary to long-term therapy with beta-blockers and thiazide diuretics, and therefore can be used for partial correction and prevention of the above shifts.

  4. Beta Blockers Suppress Dextrose-Induced Endoplasmic Reticulum Stress, Oxidative Stress, and Apoptosis in Human Coronary Artery Endothelial Cells.

    Science.gov (United States)

    Haas, Michael J; Kurban, William; Shah, Harshit; Onstead-Haas, Luisa; Mooradian, Arshag D

    Beta blockers are known to have favorable effects on endothelial function partly because of their capacity to reduce oxidative stress. To determine whether beta blockers can also prevent dextrose-induced endoplasmic reticulum (ER) stress in addition to their antioxidative effects, human coronary artery endothelial cells and hepatocyte-derived HepG2 cells were treated with 27.5 mM dextrose for 24 hours in the presence of carvedilol (a lipophilic beta blockers with alpha blocking activity), propranolol (a lipophilic nonselective beta blockers), and atenolol (a water-soluble selective beta blockers), and ER stress, oxidative, stress and cell death were measured. ER stress was measured using the placental alkaline phosphatase assay and Western blot analysis of glucose regulated protein 78, c-Jun-N-terminal kinase (JNK), phospho-JNK, eukaryotic initiating factor 2α (eIF2α), and phospho-eIF2α and measurement of X-box binding protein 1 (XBP1) mRNA splicing using reverse transcriptase-polymerase chain reaction. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. Cell viability was measured by propidium iodide staining method. The ER stress, SO production, and cell death induced by 27.5 mM dextrose were inhibited by all 3 beta blockers tested. The antioxidative and ER stress reducing effects of beta blockers were also observed in HepG2 cells. The salutary effects of beta blockers on endothelial cells in reducing both ER stress and oxidative stress may contribute to the cardioprotective effects of these agents.

  5. Effects of treatment with β-blocker and aldosterone antagonist on central and peripheral haemodynamics and oxygenation in cirrhosis

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander

    2011-01-01

    Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics and oxyg......Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with β-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics...

  6. Effects of treatment with β-blocker and aldosterone antagonist on central and peripheral haemodynamics and oxygenation in cirrhosis

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander;

    2011-01-01

    Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with ß-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics and oxyg......Patients with cirrhosis often exhibit abnormalities in cardiovascular regulation and oxygenation. Many of these patients are treated with ß-blockers and aldosterone antagonists that may influence the regulation of systemic haemodynamics, but the specific effects on systemic haemodynamics...

  7. 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

  8. 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.

  9. Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, biophysical and physiological relevance

    Institute of Scientific and Technical Information of China (English)

    Paul; Linsdell

    2014-01-01

    Dysfunction of the cystic fibrosis transmembrane con-ductance regulator(CFTR) chloride channel causes cys-tic fibrosis, while inappropriate activity of this channeloccurs in secretory diarrhea and polycystic kidney dis-ease. Drugs that interact directly with CFTR are there-fore of interest in the treatment of a number of diseasestates. This review focuses on one class of small mol-ecules that interacts directly with CFTR, namely inhibi-tors that act by directly blocking chloride movementthrough the open channel pore. In theory such com-pounds could be of use in the treatment of diarrheaand polycystic kidney disease, however in practice allknown substances acting by this mechanism to inhibitCFTR function lack either the potency or specificity forin vivo use. Nevertheless, this theoretical pharmaco-logical usefulness set the scene for the developmentof more potent, specific CFTR inhibitors. Biophysically,open channel blockers have proven most useful as ex-perimental probes of the structure and function of theCFTR chloride channel pore. Most importantly, the useof these blockers has been fundamental in developing afunctional model of the pore that includes a wide innervestibule that uses positively charged amino acid sidechains to attract both permeant and blocking anionsfrom the cell cytoplasm. CFTR channels are also subjectto this kind of blocking action by endogenous anionspresent in the cell cytoplasm, and recently this blocking effect has been suggested to play a role in the physio-logical control of CFTR channel function, in particular as a novel mechanism linking CFTR function dynamically to the composition of epithelial cell secretions. It has also been suggested that future drugs could target this same pathway as a way of pharmacologically increasing CFTR activity in cystic fibrosis. Studying open channel blockers and their mechanisms of action has resulted in significant advances in our understanding of CFTR as a pharmacological target in disease states, of

  10. Ozonation of reverse osmosis concentrate: kinetics and efficiency of beta blocker oxidation.

    Science.gov (United States)

    Benner, Jessica; Salhi, Elisabeth; Ternes, Thomas; von Gunten, Urs

    2008-06-01

    Reverse osmosis (RO) concentrate samples were obtained from a RO-membrane system that uses effluents of wastewater treatment plants (WWTP) as feed water for the production of drinking water. A number of different pharmaceuticals (e.g. antibiotics, contrast media, beta blockers) were found in the WWTP effluent as well as in the RO-concentrate. Overall, a concentration factor (feed:concentrate) of approximately 3-4 was measured. Beta blockers (acebutolol, atenolol, bisoprolol, celiprolol, metoprolol, propranolol, timolol) were found in the range of low ng/L to low microg/L. Because metoprolol and propranolol are classified as potentially toxic to aquatic organisms and all beta blocker molecules have moieties, which are reactive towards ozone (amine groups, activated aromatic rings), it was tested whether ozonation can be applied for their mitigation. Rate constants for the reaction of acebutolol, atenolol, metoprolol and propranolol with ozone and OH radicals were determined. At pH 7 acebutolol, atenolol and metoprolol react with ozone with an apparent second-order rate constant k(O)(3) of about 2,000 M(-1)s(-1), whereas propranolol reacts with approximately 10(5)M(-1)s(-1). The rate constants for the reaction of the selected compounds with OH radicals were determined to be 0.5-1.0 x 10(10)M(-1)s(-1). Experiments with RO concentrate showed that an ozone dose of only 5mg/L resulted in a quantitative removal of propranolol in 0.8s and 10mg O(3)/L oxidized 70% of metoprolol in only 1.2s. Tests with chlorinated and non-chlorinated WWTP effluent showed an increase of ozone stability but a decrease of hydroxyl radical exposure in the samples after chlorination. This may shift the oxidation processes towards direct ozone reactions and favor the degradation of compounds with high k(O)(3).

  11. COMPUTER AIDED DESIGN OF SELECTIVE CALCIUM CHANNEL BLOCKERS: USING PHARMACOPHORE - BASED AND DOCKING SIMULATIONS

    Directory of Open Access Journals (Sweden)

    Reetu

    2012-03-01

    Full Text Available In the present study, 3-D QSAR analysis was performed on the previously synthesized and evaluated derivatives of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers. Calcium Channel blockers is the molecular target responsible for the treatment of neuropathic and inflammatory pain. The 3D-QSAR study based on the principle of the alignment of pharmacophoric features by PHASE module of Schrodinger suite has been carried out on the same set of calcium channel blockers. Statistically significant 3-D QSAR model (R2=0.9288 were generated using 21 molecules in the training set. The predictive ability of model was determined using a randomly chosen test set of 6 molecules which gave predictive correlation coefficients (R2pred of 0.946 for 3-D models, indicating good predictive power. PHASE pharmacophore hypothesis AAHR.13 may correspond very closely to the interactions recorded in the active site of the ligand bound complex. These studies produced models with high correlation coefficient and good predictive abilities. Docking studies were also carried out wherein these analogues were docked into the active sites of COX-2 to analyze the receptor-ligand interactions that confer selectivity for COX-2. Compound 2 have the highest dock score (-7.28. In the active site, there are some strong hydrogen-bonding interactions observed between residues GLU67, ALA103, ASP96, SER184 and ASP22. Additionally a correlation of the quantitative structure –activity relationship data and the docking results is found to validate each other and suggest the importance of the binding step in overall drug action.

  12. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults

    Science.gov (United States)

    Anseeuw, Kurt; Cantrell, Frank Lee; Gilchrist, Ian C.; Hantson, Philippe; Bailey, Benoit; Lavergne, Valéry; Gosselin, Sophie; Kerns, William; Laliberté, Martin; Lavonas, Eric J.; Juurlink, David N.; Muscedere, John; Yang, Chen-Chang; Sinuff, Tasnim; Rieder, Michael; Mégarbane, Bruno

    2017-01-01

    Objective: To provide a management approach for adults with calcium channel blocker poisoning. Data Sources, Study Selection, and Data Extraction: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. Data Synthesis: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D–2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D). Conclusion: We offer recommendations for the stepwise management of calcium channel blocker

  13. Comparison of Alpha Blockers in Treatment of Premature Ejaculation: A Pilot Clinical Trial

    Science.gov (United States)

    Akin, Yigit; Gulmez, Hakan; Ates, Mutlu; Bozkurt, Aliseydi; Nuhoglu, Baris

    2013-01-01

    Background: Premature ejaculation (PE) is the most common sexual disorder in men and studies reported prevalence up to 30% (1, 2). PE is not a life-threatening medical condition but it influences the quality of life (QoL). Objectives: The aim of this study was to compare the efficiency, and safety of alpha blocker drugs in the treatment of patients with premature ejaculation (PE). Additionally we investigated the quality of life (QoL) in patients with PE who were treated with alpha blocker drugs. Materials and Methods: This study was a pilot clinical trial. Prospectively documented 108 patients with PE were treated and were followed-up in urology outpatient clinic. All patients were divided into 5 groups according to used alpha blocker agents which were determined by simple randomization. Silodosin 4mg (Group 1, n = 21), tamsulosin hydrochloride 0.4mg (Group 2, n = 23), alfuzosin 10mg (Group 3, n = 22), terazosin 5mg (Group 4, n = 21), doksazosin mesylate 4mg (Group5, n = 21), were used for treatment. The demographic parameters of patients, pre and post treatment intravaginal ejaculation latency time (IELT), PE Profile (PEP), and QoL index were recorded and evaluated. Effectiveness of treatment was evaluated by measuring IELT. Additionally, side effects of drugs were recorded. P IELT and decrease in PEP were provided more in Group 1 than other groups (P IELT), PE Profile (PEP), and QoL index were recorded and evaluated. Effectiveness of treatment was evaluated by measuring IELT. Additionally, side effects of drugs were recorded. P < 0.05 was considered statistically significant. PMID:24693363

  14. Incidence of medication error associated with the use of beta-blockers in Pakistan.

    Science.gov (United States)

    Nesar, Shagufta; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Rahim, Najia; Muhammad, Iyad Naeem

    2014-05-01

    Medication errors (ME) are human errors, which are very frequent in cardiovascular patients and result in patient morbidity and mortality. This study was focused to evaluate the quality of prescriptions and to emphasize the placement of clinical pharmacist in health care team. This study was carried out in different outpatient settings of (in) Karachi, Pakistan. The study period was June 2011 till June 2012. Retrospective data was analyzed for the outpatients' prescription of beta blocker drugs. During the study, prescriptions (n=450) were collected from different outpatient settings of (in) Karachi, Pakistan. Prescription containing beta-blockers were analyzed for the essential elements to be mentioned in prescription. Drug-drug interactions were identified by the Micromedex.2.0 Drug-Reax database and severity of medication error was determined by NCCMERP Index. A total of 1627 medication errors were identified in 450 prescriptions. The most frequent error was not mentioning the patient's weight (95%), followed by missing diagnosis (79.4%) and drug-drug interactions (69.5%). Twenty-two prescriptions were placed in the most severe category I (4.88%). Average number of drugs per prescription was 4.76. Significant difference was observed (χ(2)=52.418, p<0.05) using SPSS 19 for those prescription orders having more than 5 drugs with Beta-blockers. This indicates that the errors in prescription such as drug-drug interactions, wrong dose etc. was significantly increased with the number of drugs per prescription. Results showed that medication errors are very frequent in prescription written in outpatient setting of various hospitals and clinics in Karachi. This shows that the irrational prescribing is a common practice in developing countries. Placement of skilled pharmacist in the health care system is the only solution for avoidance of these medication related problems.

  15. Acrolein-mediated conduction loss is partially restored by K⁺ channel blockers.

    Science.gov (United States)

    Yan, Rui; Page, Jessica C; Shi, Riyi

    2016-02-01

    Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K(+) channels due to myelin damage leads to conduction block, and K(+) channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K(+) channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K(+) channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases.

  16. Electrically enhanced microextraction for highly selective transport of three β-blocker drugs.

    Science.gov (United States)

    Seidi, Shahram; Yamini, Yadollah; Rezazadeh, Maryam

    2011-12-15

    Facilitated transport of three β-blocker drugs including atenolol (ATE), betaxolol (BET) and propranolol (PRO) was investigated under electrical field across a supported liquid membrane (SLM) using phosphoric acid derivatives as selective ion carriers, dissolved in 2-nitro phenyl octyl ether (NPOE). In the presence of di-(2-ethylhexyl) phosphate (DEHP) and tris-(2-ethylhexyl) phosphate (TEHP) in the membrane phase, the three β-blockers showed completely different transport behaviors which enabled highly selective separation of the drugs. Each β-blocker migrated from 3 mL of sample solutions, through a thin layer of specific organic solvent immobilized in the pores of a porous hollow fiber, and into a 15 μL acidic aqueous acceptor solution present inside the lumen of the fiber. The influences of fundamental parameters affecting the transport of target drugs including type of ion carrier for selective separation of each drug and its concentration in the membrane phase, extraction voltage, time of transport, pH of donor and acceptor phases, stirring speed of donor phase and salt effect were studied and optimized. After microextraction process, the extracts were analyzed by high-performance liquid chromatography with ultraviolet detection. Under optimal conditions, ATE was selectively extracted from different saliva samples with recovery of 37%, which corresponded to preconcentration factor of 74. A good linearity was achieved for calibration curve with a coefficient of determination higher than 0.997. Limits of detection and intra-day precision (n=3) were less than 2 μg L(-1) and 8.8%, respectively.

  17. Comparative effects of sodium channel blockers in short term rat whole embryo culture

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, Mats F, E-mail: Mats.Nilsson@farmbio.uu.se [Department of Pharmaceutical Biosciences, Uppsala University (Sweden); Sköld, Anna-Carin; Ericson, Ann-Christin; Annas, Anita; Villar, Rodrigo Palma [AstraZeneca R and D Södertälje (Sweden); Cebers, Gvido [AstraZeneca R and D, iMed, 141 Portland Street, Cambridge, MA 02139 (United States); Hellmold, Heike; Gustafson, Anne-Lee [AstraZeneca R and D Södertälje (Sweden); Webster, William S [Department of Anatomy and Histology, University of Sydney (Australia)

    2013-10-15

    This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development.

  18. SU-E-I-08: Investigation of Deconvolution Methods for Blocker-Based CBCT Scatter Estimation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, C; Jin, M [University of Texas at Arlington, Arlington, TX (United States); Ouyang, L; Wang, J [UT Southwestern Medical Center at Dallas, Dallas, TX (United States)

    2015-06-15

    Purpose: To investigate whether deconvolution methods can improve the scatter estimation under different blurring and noise conditions for blocker-based scatter correction methods for cone-beam X-ray computed tomography (CBCT). Methods: An “ideal” projection image with scatter was first simulated for blocker-based CBCT data acquisition by assuming no blurring effect and no noise. The ideal image was then convolved with long-tail point spread functions (PSF) with different widths to mimic the blurring effect from the finite focal spot and detector response. Different levels of noise were also added. Three deconvolution Methods: 1) inverse filtering; 2) Wiener; and 3) Richardson-Lucy, were used to recover the scatter signal in the blocked region. The root mean square error (RMSE) of estimated scatter serves as a quantitative measure for the performance of different methods under different blurring and noise conditions. Results: Due to the blurring effect, the scatter signal in the blocked region is contaminated by the primary signal in the unblocked region. The direct use of the signal in the blocked region to estimate scatter (“direct method”) leads to large RMSE values, which increase with the increased width of PSF and increased noise. The inverse filtering is very sensitive to noise and practically useless. The Wiener and Richardson-Lucy deconvolution methods significantly improve scatter estimation compared to the direct method. For a typical medium PSF and medium noise condition, both methods (∼20 RMSE) can achieve 4-fold improvement over the direct method (∼80 RMSE). The Wiener method deals better with large noise and Richardson-Lucy works better on wide PSF. Conclusion: We investigated several deconvolution methods to recover the scatter signal in the blocked region for blocker-based scatter correction for CBCT. Our simulation results demonstrate that Wiener and Richardson-Lucy deconvolution can significantly improve the scatter estimation

  19. Leukocyte redistribution: effects of beta blockers in patients with chronic heart failure.

    Directory of Open Access Journals (Sweden)

    Stephan von Haehling

    Full Text Available BACKGROUND: Overproduction of pro-inflammatory cytokines is a well established factor in the progression of chronic heart failure (CHF. Changes in cellular immunity have not been widely studied, and the impact of standard medication is uncertain. Here we investigate whether a leukocyte redistribution occurs in CHF and whether this effect is influenced by beta-blocker therapy. METHODOLOGY: We prospectively studied 75 patients with systolic CHF (age: 68+/-11 years, left ventricular ejection fraction 32+/-11%, New York Heart Association class 2.5+/-0.7 and 20 age-matched healthy control subjects (age: 63+/-10 years. We measured the response of cells to endotoxin exposure in vitro, analysed subsets of lymphocytes using flow cytometry, and assessed plasma levels of the pro-inflammatory markers interleukin 1, 6, tumor necrosis factor-alpha, and soluble tumor necrosis factor receptors 1 and 2. PRINCIPAL FINDINGS: While no differences in the number of leukocytes were noted between patients with CHF and healthy controls, we detected relative lymphopenia in patients with CHF (p<0.001 vs. control, mostly driven by reductions in T helper cells and B cells (both p<0.05. The number of neutrophils was increased (p<0.01. These effects were pronounced in patients who were beta-blocker naïve (32% of all patients with CHF. Increased plasma levels of soluble tumor necrosis receptor-1 correlated with the relative number of lymphocyte subsets. CONCLUSIONS: In patients with CHF, we detected a redistribution of leukocyte subsets, i.e. an increase in neutrophils with relative lymphopenia. These effects were pronounced in patients who were beta-blocker naïve. The underlying mechanism remains to be elucidated.

  20. 替米沙坦对东莨菪碱模型小鼠学习记忆及脑内胆碱能神经的影响%Effects of telmisartan on learning-memory and brain cholinergic nerve in scopolamine-induced model of mice

    Institute of Scientific and Technical Information of China (English)

    李冰; 王浩; 洪浩

    2013-01-01

    OBJECTIVE To investigate the effects of telmisartan on learning-memory and brain cholinergic nerve in scopolamine-induced model of mice. METHODS Mice were randomly divided into 5 groups: normal control, scopolamine model, Aricept group (positive control) , high and low doses of telmisartan group (0. 70,0. 35 mg·kg-1·d-1 ). Telmisartan was orally administered after intraperitoneal injection with scopolamine (1.0 mg·kg-1·d-1). Learning-memory function was evaluated by Morris water maze test and Y maze test respectively. Changes in cholinergic system reactivity were also examined by measuring the acetylcholine (ACh) and acetylcholinesterase (AChE) in the hippocampus and cortex. RESULTS Compared with model group, treatment with telmisartan (0. 70,0. 35 mg·kg-1·d-1) significantly decreased the escape latency in invisible platform test, increased the time spent in the platform quadrant in the spatial probe test and the number of crossing times in the Morris water maze test, and increased the times of correct responses in the Y maze test. Telmisartan also significantly decreased AChE activity and increased ACh level in the hippocampus and cortex. CONCLUSION Telmisartan may improve learning-memory impairment induced by scopolamine through elevation of brain ACh levels resulting from inhibition of AChE activity in mice.%目的:探究替米沙坦对东莨菪碱模型小鼠学习记忆及脑内胆碱能神经的影响.方法:将小鼠按体质量随机分为5组:正常对照组(Sal+ Veh)、东莨菪碱模型组(Sco+ Veh)、多奈哌齐组(Sco+ Ari)、替米沙坦高剂量组(Sco+ Tel 0.70 mg·kg-1)及低剂量组(Sco+ Tel 0.35 mg·kg-1),灌胃给药,除正常对照组腹腔注射生理盐水外,其他各组注射东莨菪碱.采用Morris水迷宫和Y迷宫试验评价学习记忆能力,并测定脑内乙酰胆碱(ACh)、乙酰胆碱酯酶(AChE)水平.结果:替米沙坦(0.70,0.35 mg·kg-1·d-1)能显著缩短东莨菪碱模型鼠在隐藏平台试验的潜伏期,增加

  1. PRISMA-combined α-blockers and antimuscarinics for ureteral stent-related symptoms

    Science.gov (United States)

    Zhang, Yu-ming; Chu, Pei; Wang, Wen-jin

    2017-01-01

    Abstract Background: As a monotherpay, a-blockers and anti-muscarinics are both efficacy for ureteral stent-related symptoms (SRS). The aim of the study was to systematically evaluate their efficacy of a combination therapy for SRS. Methods: Relevant studies investigating α-blockers and/or anti-muscarinics for SRS were identified though searching online databases including PubMed, EMBASE, Cochrane Library, and other sources up to March 2016. The RevMan software was used for data analysis, and senesitivity analysis and inverted funnel plot were also adopted. Results: Seven randomized controlled trials (RCTs) and 1 prospective controlled trial including 545 patients were selected. Compared with α-blockers, the combination group achieved significant improvements in total International Prostate Symptom Score (IPSS) [–3.93 (2.89, 4.96), P < 0.00001], obstructive subscore [–1.29 (0.68, 1.89), P < 0.0001], irritative subscore [–2.93 (2.18, 3.68), P < 0.00001], and quality of life score [–0.99 (0.42, 1.55), P < 0.001]. Compared with antimuscarinics, there were also significant differences in total IPSS [–3.49 (2.43, 4.55), P < 0.00001], obstructive subscore [–1.40 (0.78, 2.01), P < 0.00001], irritative subscore [–2.10 (1.30, 2.90), P < 0.00001], and quality of life score [–1.18 (0.58, 1.80), P < 0.001] in favor of combination group. No significant difference was found in the visual analog pain score and the urinary symptoms score in Ureteral Stent Symptom Questionnaire (USSQ). No significant difference in complications was found. Conclusions: Current analysis shows significant advantages of combination therapy compared with monotherapy of α-blockers or antimuscarinics alone mainly based on IPSS. More RCTs adopting validated USSQ as outcome measures are warranted to support the finding. PMID:28207522

  2. POSITIONS OF CALCIUM CHANNEL BLOCKER LERCANIDIPINE ACCORDING TO EVIDENCE BASED CARDIOLOGY

    Directory of Open Access Journals (Sweden)

    Yu. V. Lukina

    2010-01-01

    Full Text Available Data of evidence based cardiology including results of international clinical trials on efficacy and safety of the modern calcium channel blocker (CCB, lercanidipine, are presented. Results of these trials show the firm position of lercanidipine in the modern cardiology and confirm that treatment with lercanidipine leads to significant reduction of systolic and diastolic blood pressure (BP with no effect on heart rate (HR. Peripheral edema (the common side effect of CCBs occurs rarer with lercanidipine treatment than this with any other CCB treatment. Lercanidipine can be recommended to patients with concomitant diseases due to its additional features.

  3. Clinical Pharmacology of Alpha-1 Blockers Improving Drug-profile through Novel Formulations.

    Science.gov (United States)

    Nerurkar, Rajan P; Ved, Jignesh K

    2014-09-01

    Clinical pharmacology is an essential consideration in chronic therapies, and may play a significant role in modifying the pharmacological characteristics of drug formulations. Improvement in drug formulations may ensure their safe and effective use over a period of time. This has been particularly observed with α-1 adrenergic blockers in hypertension management. Advancements in formulations like prazosin GITS, have resulted in improvement in tolerability profile and smoother, more effective blood pressure control, which reasonably translate into improvement in patient compliance and better clinical outcomes.

  4. Alpha blocker prazosin for the treatment of benign prostatic hypertrophy (BPH.

    Directory of Open Access Journals (Sweden)

    Punekar S

    1995-10-01

    Full Text Available In this study medical treatment with alpha blocker-prazosin is compared with transurethral resection of prostate (TURP in 62 patients suffering from benign enlargement of prostate with a gland size of less than 20 gms. After thorough interrogation patients were offered either TURP or prazosin therapy. Symptom scoring, residual volume of urine and urinary flow rates were estimated in both the groups before and 3 months after the therapy. 23.5% patients in prazosin group while 90% of patients in TURP group had significant improvement. This distinctly brings out the superiority of TURP for benign enlargement of prostate.

  5. Anticonvulsant activity of gap-junctional blocker carbenoxolone in albino rats

    Directory of Open Access Journals (Sweden)

    Suneel Kumar Reddy

    2014-08-01

    Conclusions: Carbenoxolone has in-vivo anticonvulsive effect and could be useful in both petitmal (absence seizures and grand mal (generalized tonic-clonic epilepsy seizures. The protective effect of carbenoxolone could be due to blockade of GJ channels that mediate electro tonic coupling and thereby prevent the neural synchronization that is characteristic of seizures. The study also supports the view that GJs have a functional role in the electrophysiology of seizures and GJ blockers have potential as a new class of antiepileptic drugs. [Int J Basic Clin Pharmacol 2014; 3(4.000: 711-717

  6. Participation of histamine in the step-through active avoidance response and its inhibition by H1-blockers.

    Science.gov (United States)

    Kamei, C; Tasaka, K

    1991-12-01

    The effects of intravenous and intracerebroventricular administrations of certain H1-blockers on the active avoidance response in rats were studied. Among the classic H1-blockers used in this study: pyrilamine, diphenydramine, promethazine and chlorpheniramine, promethazine was the most effective and chlorpheniramine the least in inhibiting the active avoidance response; namely, a variation of prolongation in the response latency of the avoidance response. Meanwhile, ketotifen most potently inhibited the active avoidance response when the drugs were administered intracerebroventricularly. Mequitazine, astemizole and oxatomide were weak depressants when administered by either route. Azelastine was less effective than the classic H1-blockers by intravenous injection, while by intracerebroventricular injection, the inhibition was almost identical to those induced by the classic H1-blockers. Intracerebroventricular injection of histamine was antagonized the prolonged latency in the avoidance response induced by pyrilamine or diphenhydramine. A similar effect was also produced by 2-methylhistamine, but 4-methylhistamine had no effect. Intracerebroventricular injection of acetylcholine was restored the retarded avoidance response induced by pyrilamine, but a dose 20 times greater than that of histamine was required. From these findings, it can be concluded that inhibition of the active avoidance response induced by H1-blockers may be exerted through interaction with H1-receptors in the brain.

  7. 替米沙坦对大鼠IgA肾病模型肾小管间质损伤及PPARγ表达的影响%Effect of telmisartan on tubulointerstital injury and expression of PPARγin rat renal tissue of IgA nephropathy model

    Institute of Scientific and Technical Information of China (English)

    邢丽; 柏林; 禹程远; 解汝娟

    2010-01-01

    Objective To observe the effect of telmisartan on the expression of PPARγin rat renal tissue of IgA nephropathy model and clarify the possible mechanism of telmisartan in tubulointerstitial injury.Methods The experimental rat model with IgA nephropathy was induced by bovine serum albumin ( BSA),lipopolysaccharide(LPS)and carbon tetrachloride(CCl4). Forty male SD rats were randomly divided into control group, IgA model group, rosiglitazone group, telmisartan group and losartan group. At preadministration, Weeks 4, 8 and 10, the quantity of 24-hour proteinuria was measured. The morphologic changes of renal tissues were evaluated by electron microscope. Immunohistochemistry was used to observe the expressions of PPARγ, TGF-β1 and α-smooth muscle actin (α-SMA) in different groups and RT-PCR to detect the expressions of PPARγ, TGF-β1 and monocyte chemoattractant protein-1 ( MCP-1 ) in different groups. Results Compared with control group, 24-hour proteinuria(mg) increased markedly in IgA model group( 14. 14 ± 1.99 vs 1.59 ±0. 18), but rosiglitazone group(2. 35 ±0. 33), telmisartan group( 1.88 ±0. 09)and losartan group( 2. 82 ± 0. 34 ) was much lower and telmisartan had the most significant effect (all P <0. 05). Compared with control group, there were varying degrees of mesangial proliferation and infiltration of inflammatory cell in IgA model group(3. 10 ±0. 18). The tubulointerstitial injury was notably alleviated in rosiglitazone group( 1.97 ±0. 23), telmisartan group( 1.57 ±0. 14) and losartan group (2. 15 ±0. 22) while telmisartan had the most significant effect (all P < 0.01 =. With immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), PPARγ, TGF-β1, α-SMA and MCP-1 had minimal expression on tubule and interstitium in normal group. But there was a high expression in model group. There was no difference between losartan and model groups. There was a lowered expression in rosiglitazone and telmisartan groups

  8. [Treatment of arrhythmia in coronary patients and hypertensives with beta blockers and Depasan retard].

    Science.gov (United States)

    Kandziora, J

    1981-05-14

    In the ambulatory of an internal specialist a number of patients suffering from angina pectoris or hypertonia together with arrhythmic troubles received an initial treatment with beta-blockers over a period of 21 days. In cases in which arrhythmia persisted after this initial period the treatment was continued for another 21 days with the addition of Depasan retard in function of a second medicament. This combined treatment in form of an open study was extended to a total number of 50 patients presenting ventricular extrasystolia in 45 cases and in 5 cases absolute arrhythmia in addition to the main disease. Treatment with Depasan retard showed good or satisfactory results in 39 out of 45 patients suffering from ventricular extrasystoles, whilst no effect could be obtained in the 5 cases with absolute arrhythmia. No signs of incompatibility or unwanted interactions were observed in the course of this open study. Based on these results it can be concluded that Depasan retard should be recommended in those cases where on account of persistent arrhythmical troubles and especially extrasystoles, during a treatment with beta-blockers in patients suffering from angina pectoris or hypertonia, and additional treatment with anti-arrhythmical medicaments appears to be indicated.

  9. Positive symptoms in multiple sclerosis: their treatment with sodium channel blockers, lidocaine and mexiletine.

    Science.gov (United States)

    Sakurai, M; Kanazawa, I

    1999-01-15

    Patients with multiple sclerosis (MS) often show positive symptoms of painful tonic seizure and dysesthesia as well as negative symptoms of paralysis and hypesthesia. Positive manifestation is paroxysmal and/or persistent. These are considered to be mediated by ectopic impulses generated at the site of demyelination, whereas negative symptoms are caused by conduction block. Conduction block at a demyelinated segment should reduce positive symptoms, but worsen negative ones. As reported previously, lidocaine, an Na channel blocker unmasks silent negative symptoms presumably by further reducing the action current in demyelinated portions and blocking conduction. Furthermore, because it blocks Na channels in a voltage- and frequency dependent manner, fibers that mediate positive symptoms are preferentially blocked. We administered lidocaine to 30 MS patients with positive symptoms. Lidocaine (mean plasma level, 2.4 pg/ml) almost completely abolished the paroxysmal manifestation of painful tonic seizures, neuralgic attacks, paroxysmal itching, and Lhermitte's sign. It also markedly alleviated persistent symptoms, but less so than paroxysmal symptoms. Similar effects were obtained with orally-administered mexiletine (300-400 mg/day), a derivative of lidocaine, but to a lesser extent. Na channel blockers have a dual effect on symptoms in MS, depending on whether symptoms are positive or negative. The mechanism that produces positive symptoms and the effects of the drugs on these symptoms are discussed.

  10. The pre-synaptic blocker toosendanin does not inhibit secretion in exocrine cells

    Institute of Scientific and Technical Information of China (English)

    Zong-Jie Cui; Xue-Hui He

    2002-01-01

    AIM: Toosendanin is a pre-synaptic blocker at theneuromuscular junction and its inhibitory effect is dividedinto an initial facilitative/stimulatory phase followed by aprolonged inhibitory phase. The present study investigatedwhether the subsequent inhibitory phase was due toexhaustion of the secretory machinery as a result of extensivestimulation during the initial facilitative phase. Morespecifically, this paper examined whether toosendanin coulddirectly inhibit the secretory machinery in exocrine cells.METHODS: Rat pancreatic acinar cells were isolated bycollagenase digestion. Secretion was assessed by measuringthe amount of amylase released into the extracellular mediumas a percentage of the total present in the cells beforestimulation. Cholecystokinin (CCK)-induced increases inintracellular calcium in single cells were measured with fura-2 microfluorometry.RESULTS: Effects of toosendanin on CCK-induced amylasesecretion and calcium oscillations were investigated.Toosendanin of 87-870 tM had no effect on 10 pM-100 nMCCK-stimulated amylase secretion, nor did 8.7-870 μMtoosendanin inhibit 5 pM CCK-induced calcium oscillations.In contrast, 10 nM CCK1 receptor antagonist FK 480 completelyblocked 5 pM CCK-induced calcium oscillations.CONCLUSION: The pre-synaptic "blocker" toosendanin is aselective activator of the voltage-dependent calcium channels,but does not interfere with the secretory machinery itself.

  11. Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons.

    Science.gov (United States)

    Hlubek, M D; Cobbett, P

    2000-09-15

    Recordings were made from magnocellular neuroendocrine cells dissociated from the supraoptic nucleus of the adult guinea pig to determine the role of voltage gated K(+) channels in controlling the duration of action potentials and in mediating frequency-dependent action potential broadening exhibited by these neurons. The K(+) channel blockers charybdotoxin (ChTx), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) increased the duration of individual action potentials indicating that multiple types of K(+) channel are important in controlling action potential duration. The effect of these K(+) channel blockers was almost completely reversed by simultaneous blockade of voltage gated Ca(2+) channels with Cd(2+). Frequency-dependent action potential broadening was exhibited by these neurons during trains of action potentials elicited by membrane depolarizing current pulses presented at 10 Hz but not at 1 Hz. 4-AP but not ChTx or TEA inhibited frequency-dependent action potential broadening indicating that frequency-dependent action potential broadening is dependent on increasing steady-state inactivation of A-type K(+) channels (which are blocked by 4-AP). A model of differential contributions of voltage gated K(+) channels and voltage gated Ca(2+) channels to frequency-dependent action potential broadening, in which an increase of Ca(2+) current during each successive action potential is permitted as a result of the increasing steady-state inactivation of A-type K(+) channels, is presented.

  12. A transcription blocker isolated from a designed repeat protein combinatorial library by in vivo functional screen.

    Science.gov (United States)

    Tikhonova, Elena B; Ethayathulla, Abdul S; Su, Yue; Hariharan, Parameswaran; Xie, Shicong; Guan, Lan

    2015-01-28

    A highly diverse DNA library coding for ankyrin seven-repeat proteins (ANK-N5C) was designed and constructed by a PCR-based combinatorial assembly strategy. A bacterial melibiose fermentation assay was adapted for in vivo functional screen. We isolated a transcription blocker that completely inhibits the melibiose-dependent expression of α-galactosidase (MelA) and melibiose permease (MelB) of Escherichia coli by specifically preventing activation of the melAB operon. High-resolution crystal structural determination reveals that the designed ANK-N5C protein has a typical ankyrin fold, and the specific transcription blocker, ANK-N5C-281, forms a domain-swapped dimer. Functional tests suggest that the activity of MelR, a DNA-binding transcription activator and a member of AraC family of transcription factors, is inhibited by ANK-N5C-281 protein. All ANK-N5C proteins are expected to have a concave binding area with negative surface potential, suggesting that the designed ANK-N5C library proteins may facilitate the discovery of binders recognizing structural motifs with positive surface potential, like in DNA-binding proteins. Overall, our results show that the established library is a useful tool for the discovery of novel bioactive reagents.

  13. Acute effect of calcium blocker on renal hemodynamics in diabetic spontaneously hypertensive rat.

    Science.gov (United States)

    Kaizu, K; Ling, Q Y; Uriu, K; Ikeda, M; Eto, S

    1995-01-01

    This study was done to examine the acute effect of a calcium channel blocker on renal hemodynamics in the diabetic spontaneously hypertensive rat (SHR). Streptozotocin was used to induce diabetes, and barnidipine (B) was used as a calcium blocker. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by a clearance method with paraaminohypurate (PAH) and inulin, respectively. Rats were divided into two groups: nondiabetic SHR, N-SHR; diabetic SHR, DM-SHR. B increased RBF in N-SHR (7.44 +/- 1.99 versus 8.50 +/- 1.97 mL/min/g.kw) while there was no change in DM-SHR. B reduced renovascular resistance (RVR) in DM-SHR and N-SHR. B increased GFR in N-SHR (1.15 +/- 0.24 versus 1.34 +/- 0.25 mL/min/g.kw), in spite of no changes in DM-SHR. B did not modify filtration fraction (FF) in both groups. These results indicate (1) in SHR, B exerts beneficial effects on hypertensive renal damage by reducing mean arterial pressure (MAP), RVR, RBF, and GFR; (2) in diabetic SHR, B is less effective in restoring renal hyperfiltration in spite of reducing RVR.

  14. An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure.

    Science.gov (United States)

    Thorneloe, Kevin S; Cheung, Mui; Bao, Weike; Alsaid, Hasan; Lenhard, Stephen; Jian, Ming-Yuan; Costell, Melissa; Maniscalco-Hauk, Kristeen; Krawiec, John A; Olzinski, Alan; Gordon, Earl; Lozinskaya, Irina; Elefante, Lou; Qin, Pu; Matasic, Daniel S; James, Chris; Tunstead, James; Donovan, Brian; Kallal, Lorena; Waszkiewicz, Anna; Vaidya, Kalindi; Davenport, Elizabeth A; Larkin, Jonathan; Burgert, Mark; Casillas, Linda N; Marquis, Robert W; Ye, Guosen; Eidam, Hilary S; Goodman, Krista B; Toomey, John R; Roethke, Theresa J; Jucker, Beat M; Schnackenberg, Christine G; Townsley, Mary I; Lepore, John J; Willette, Robert N

    2012-11-01

    Pulmonary edema resulting from high pulmonary venous pressure (PVP) is a major cause of morbidity and mortality in heart failure (HF) patients, but current treatment options demonstrate substantial limitations. Recent evidence from rodent lungs suggests that PVP-induced edema is driven by activation of pulmonary capillary endothelial transient receptor potential vanilloid 4 (TRPV4) channels. To examine the therapeutic potential of this mechanism, we evaluated TRPV4 expression in human congestive HF lungs and developed small-molecule TRPV4 channel blockers for testing in animal models of HF. TRPV4 immunolabeling of human lung sections demonstrated expression of TRPV4 in the pulmonary vasculature that was enhanced in sections from HF patients compared to controls. GSK2193874 was identified as a selective, orally active TRPV4 blocker that inhibits Ca(2+) influx through recombinant TRPV4 channels and native endothelial TRPV4 currents. In isolated rodent and canine lungs, TRPV4 blockade prevented the increased vascular permeability and resultant pulmonary edema associated with elevated PVP. Furthermore, in both acute and chronic HF models, GSK2193874 pretreatment inhibited the formation of pulmonary edema and enhanced arterial oxygenation. Finally, GSK2193874 treatment resolved pulmonary edema already established by myocardial infarction in mice. These findings identify a crucial role for TRPV4 in the formation of HF-induced pulmonary edema and suggest that TRPV4 blockade is a potential therapeutic strategy for HF patients.

  15. Predictors of response to TNF blockers in patients with polyarticular psoriatic arthritis.

    Science.gov (United States)

    Carvalho, Pedro David; Duarte, Cátia; Vieira-Sousa, Elsa; Cunha-Miranda, Luís; Avila-Ribeiro, Pedro; Santos, Helena; Bernardes, Miguel; Santos, Maria José; Cerqueira, Marcos; Mateus, Margarida; Nero, Patrícia; Águeda, Ana; Silva, José António Pereira da; Machado, Pedro

    2017-01-01

    Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease with a broad clinical spectrum. PsA can affect the axial skeleton, peripheral joints, entheses, synovial sheaths of tendons, skin, nails and extra-articular organs. Tumour necrosis factor alpha blockers (TNF blockers) were a breakthrough development in the treatment of PsA. Identifying predictors of response to biological therapies in patients with PsA is of utmost importance, especially in view of the costs and potential side effects of these agents. The aims of the present study were to determine baseline predictive factors of response to biological therapies, at 3 and 6 months, in PsA patients with polyarticular involvement (with or without axial involvement). Data were collected from the Rheumatic Diseases Portuguese Register (Reuma.pt). Eligible patients had to be anti-TNF-naive at baseline and to have at least 3 months of follow-up after the beginning of TNF blocker therapy. Only patients with information on at least one of the response measures (at 3 or 6 months of follow-up) were included in the analysis. Univariable logistic regression analysis of potential baseline predictors of European League Against Rheumatism (EULAR) good clinical response, EULAR good/moderate response, 28-joint Disease Activity Score with three variables including the erythrocyte sedimentation rate (DAS28-3V-ESR) remission and Health Assessment Questionnaire (HAQ) response were performed. Multivariable logistic regression using a forward selection procedure was used until the best-fit model was obtained, taking confounding effects into account. A total of 180 patients were eligible for the study (mean age 52 years, 54% women). In multivariable analysis at 3 months, females were less likely to attain a good EULAR response [OR=0.082 (95% CI=0.024, 0.278)], a DAS28-3V-ESR remission [OR=0.083 (95% CI=0.017, 0.416)], a moderate or good EULAR response [OR=0.091 (95% CI=0.011, 0.091)] and a HAQ response [OR=0.074 (95% CI

  16. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

    Science.gov (United States)

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  17. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Rasmussen, Jeppe Nørgaard; Abildstrøm, Steen Z

    2006-01-01

    AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995...... and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were...... still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials...

  18. Treatment with oral beta-blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction

    DEFF Research Database (Denmark)

    Ersbøll, A S; Hedegaard, M; Søndergaard, L

    2014-01-01

    OBJECTIVE: To investigate the effect on fetal growth of treatment with oral beta-blockers during pregnancy in women with congenital or acquired heart disease. DESIGN: Historical matched cohort study. SETTING: Centre for Pregnant Women with Heart Disease, Copenhagen University Hospital, Denmark....... POPULATION: A cohort of 175 women with heart disease, grouped according to beta-blocker treatment, and a cohort of 627 women from the overall population matched on seven birthweight-determining factors. METHODS: Differences between groups were tested by simple descriptive statistics and assessed using...... standard hypothesis tests. Associations were estimated by correlational analysis and multivariable regression. MAIN OUTCOME MEASURE: Proportion of infants born small for gestational age (SGA). RESULTS: More of the infants exposed to beta-blockers were SGA compared with non-exposed infants (29.4 versus 15...

  19. Intermediate and long-term memories of associative learning are differentially affected by transcription versus translation blockers in Lymnaea.

    Science.gov (United States)

    Sangha, Susan; Scheibenstock, Andi; McComb, Chloe; Lukowiak, Ken

    2003-05-01

    Aerial respiratory behaviour in the pond snail, Lymnaea stagnalis, can be operantly conditioned. This associative learning then undergoes consolidation into a long-lasting memory which, depending on the training procedure used, causes intermediate-term memory (ITM; lasting 3 h) or long-term memory (LTM; lasting >6 h) to be formed. We determined the differential susceptibility of these two forms of memory to translation and transcription blockers. The injection of a translation blocker, Anisomycin, 2.5 h before training prevents the establishment of both ITM and LTM. On the other hand, injection of the transcription blocker Actinomycin D, 2.5 h before training, did not prevent the establishment of ITM, but did, however, prevent LTM formation. Thus in Lymnaea, following associative learning, both ITM and LTM are dependent on new protein synthesis. ITM appears to be dependent on protein synthesis from preexisting transcription factors, whilst LTM is dependent on protein synthesis from new transcription messages.

  20. The effects of beta-blockers on dobutamine-atropine stress echocardiography: early protocol versus standard protocol

    Directory of Open Access Journals (Sweden)

    Weitzel Luis H

    2006-07-01

    Full Text Available Abstract Background To study the effects of Beta-blockers during Dobutamine Stress Echocardiography (DSE comparing the hemodynamic benefits of an early administration of atropine in patients taking or not Beta-blockers. Methods One hundred and twenty-one patients were submitted to dobutamine stress echocardiography for the investigation of myocardial ischemia. The administration of atropine was randomized into two groups: A or B (early protocol when atropine was administered at 10 and 20 mcg/kg/min of dobutamine, respectively and C (standard protocol with atropine at 40 mcg/kg/min of dobutamine. Analysis of the effects of Beta-blockers was done regarding the behavior pattern of heart rate and blood pressure, test time, number of conclusive and inconclusive (negative sub-maximum test results, total doses of atropine and dobutamine, and general complications. Results Beta-blocked patients who received early atropine (Group A&B had a significantly lower double product (p = 0.008, a higher mean test time (p = 0.010 and required a higher dose of atropine (p = 0.0005 when compared to the patients in this group who were not Beta-blocked. The same findings occurred in the standard protocol (Group C, however the early administration of atropine reduced test time both in the presence and absence of this therapy (p = 0.0001. The patients with Beta-blockers in Group A&B had a lower rate of inconclusive tests (26% compared to those in Group C (40%. Complications were similar in both groups. Conclusion The chronotropic response during dobutamine stress echocardiography was significantly reduced with the use of Beta-blockers. The early administration of atropine optimized the hemodynamic response, reduced test time in patients with or without Beta-blockers and reduced the number of inconclusive tests in the early protocol.

  1. T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers

    Science.gov (United States)

    Fung-Leung, Wai-Ping; Edwards, Wilson; Liu, Yi; Ngo, Karen; Angsana, Julianty; Castro, Glenda; Wu, Nancy; Liu, Xuejun; Swanson, Ronald V.; Wickenden, Alan D.

    2017-01-01

    Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers. PMID:28107393

  2. 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.

  3. [Effect of calcium channel blockers on developing nervous syndrome of high pressure and nitrogen narcosis in mice].

    Science.gov (United States)

    Sledkov, A I

    1997-01-01

    In the experiments conducted on mice which prior to compression in a heliox environment have been injected the blockers of various types of calcium channels (flunarezine, verapramil and nifedipine) as well as bemethyl (actoprotector) and oxymethacye (antioxidant) there escaped detection of noticeable effect of these drugs on developing the high pressure nervous syndrome (HPNS). On exposure to the hyperbaric nitrogen-oxygen environment verapromil (phenylalkulamine blocker of L-type calcium channels) had a protection effect with respect to a convulsive component of the nitrogen narcosis.

  4. Benefit of combination β-blocker and endoscopic treatment to prevent variceal rebleeding: A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Natalie; Funakoshi; Frédérique; Ségalas-Largey; Yohan; Duny; Frédéric; Oberti; Jean-Christophe; Valats; Michael; Bismuth; Jean-Pierre; Daurès; Pierre; Blanc

    2010-01-01

    AIM: To determine whether the association of β-blockers with endoscopic treatment is superior to endoscopic treatment alone for the secondary prophylaxis of oesophageal variceal bleeding. METHODS: Randomised controlled trials comparing sclerotherapy (SCL) with SCL plus β-blockers (BB) or banding ligation (BL) with BL plus BB were identif ied.Main outcomes were overall and 6, 12 and 24 mo rebleeding rates, as well as overall and 6, 12 and 24 mo mortality. Two statistical methods were used: Yusuf-Peto, and De...

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

    Science.gov (United States)

    Laviano, Alessandro

    2016-01-01

    Abstract 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. PMID:27625919

  6. ACE inhibition is superior to angiotensin receptor blockade for renography in renal artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Karanikas, Georgios; Becherer, Alexander; Wiesner, Karoline; Dudczak, Robert; Kletter, Kurt [Department of Nuclear Medicine, University of Vienna (Austria)

    2002-03-01

    Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much more sensitive than valsartan renography in detecting a clinically significant renal artery stenosis. Furthermore, our data suggest that other effects, such as that on the prostaglandin-bradykinin system, are of at least similar importance to ACE inhibition for the high diagnostic sensitivity of captopril renography regarding renovascular hypertension. (orig.)

  7. Maternal nutrient restriction and the fetal left ventricle: Decreased angiotensin receptor expression

    Directory of Open Access Journals (Sweden)

    Lang Alvin L

    2005-07-01

    Full Text Available Abstract Background Adequate maternal nutrition during gestation is requisite for fetal nutrition and development. While a large group of epidemiological studies indicate poor fetal nutrition increases heart disease risk and mortality in later life, little work has focused on the effects of impaired maternal nutrition on fetal heart development. We have previously shown that 50% global nutrient restriction from 28–78 days of gestation (early to mid-pregnancy; term = 147 days in sheep at mid-gestation retards fetal growth while protecting growth of heart and results in hypertensive male offspring at nine months of age. In the present study, we evaluate LV gene transcription using RNA protection assay and real-time reverse transcriptase polymerase chain reaction, and protein expression using western blot, of VEGF and AT1 and AT2 receptors for AngII at mid-gestation in fetuses from pregnant ewes fed either 100% (C or 50% (NR diet during early to mid-gestation. Results No difference between the NR (n = 6 and C (n = 6 groups was found in gene transcription of the AngII receptors. Immunoreactive AT1 (1918.4 +/- 154.2 vs. 3881.2 +/- 494.9; P Conclusion The present study demonstrates that VEGF, AT1 and AT2 message and protein are not tightly coupled, pointing to post-transcriptional control points in the mid gestation NR fetus. The present data also suggest that the role of VEGF and the renin-angiotensin system receptors during conditions inducing protected cardiac growth is distinct from the role these proteins may play in normal fetal cardiac growth. The present findings may help explain epidemiological studies that indicate fetuses with low birth weight carry an increased risk of mortality from coronary and cardiovascular disease, particularly if these individuals have reduced cardiovascular reserve due to an epigenetic decrease in vascularization.

  8. Differential roles of Angiotensinogen and Angiotensin Receptor type 1 polymorphisms in breast cancer risk.

    NARCIS (Netherlands)

    Gonzalez-Zuloet Ladd, A.M.; Arias Vasquez, A.; Siemes, C.; Yazdanpanah, M.; Coebergh, J.W.W.; Hofman, A.; Stricker, B.H.C.; Duijn, C.M. van

    2007-01-01

    While angiotensinogen (AGT) seems to have anti proliferative properties, angiotensin II (ATII) is a potent growth factor and it mediates its actions through the angiotensin type 1 receptor (AGTR1). In the AGT gene, the M235T polymorphism has been associated with the variation in angiotensinogen leve

  9. Predicting Kinase Activity in Angiotensin Receptor Phosphoproteomes Based on Sequence-Motifs and Interactions

    DEFF Research Database (Denmark)

    Bøgebo, Rikke; Horn, Heiko; Olsen, Jesper V;

    2014-01-01

    -arrestin dependent signalling. Two complimentary global phosphoproteomics studies have analyzed the complex signalling induced by the AT1aR. Here we integrate the data sets from these studies and perform a joint analysis using a novel method for prediction of differential kinase activity from phosphoproteomics data......Recent progress in the understanding of seven-transmembrane receptor (7TMR) signalling has promoted the development of a new generation of pathway selective ligands. The angiotensin II type I receptor (AT1aR) is one of the most studied 7TMRs with respect to selective activation of the β...... likely activated kinases. This suggested that AT1aR-dependent signalling activates 48 of the 285 kinases detected in HEK293 cells. Of these, Aurora B, CLK3 and PKG1 have not previously been described in the pathway whereas others, such as PKA, PKB and PKC, are well known. In summary, we have developed...

  10. Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial

    DEFF Research Database (Denmark)

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

    2010-01-01

    . Secondary outcome variables: Secondary effect variables include • the Barthel index (functional status) • EuroQol (quality of life) and • Mini-mental state examination (cognition) at 6-months • Health economic costs during the first 6-months FUNDING: The Scandinavian Candesartan Acute Stroke Trial receives......-European countries: Norway, Sweden, Denmark, Belgium, Germany, Poland, Lithuania, Estonia and Finland. STUDY OUTCOMES: There are two co-primary effect variables: • Functional status at 6-months, measured by the modified Rankin Scale, and • vascular death, myocardial infarction or stroke during the first 6-months...

  11. Intrarenal renin-angiotensin system modulates glomerular angiotensin receptors in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Wilkes, B.M.; Pion, I.; Sollott, S.; Michaels, S.; Kiesel, G. (North Shore Univ. Hospital and Cornell Univ. Medical College, Manhasset, NY (USA))

    1988-03-01

    The aim of this study was to test the hypothesis that the intrarenal renin-angiotensin system (RAS) modulates glomerular angiotensin II (ANG II) receptors. In one protocol ANG II receptors were measured 7 days after unilateral denervation of the left kidney in rats. There were 50% more receptors in the glomeruli from denervated compared with innervated kidneys, which was associated with a 63% reduction in left renal vein renin. The differences in ANG II receptors between the left and right kidneys were not longer present when angiotensin-converting enzyme was inhibited with enalapril or when pharmacological amounts of ANG II were infused. In a second protocol, renal cortical renin content was raised in the left kidney by placing a 0.20-mm clip on the left renal artery. At 7 days, glomerular ANG II receptors were reduced by 72.3% in the clipped compared with the contralateral kidneys. The differences in ANG II receptors were no longer present after enalapril treatment. Pharmacological maneuvers that either blocked ANG II formation or increased circulating ANG II resulted in an equal number of ANG II receptors in the right and left kidneys. The data indicate that the intrarenal RAS modulates the density of glomerular ANG II receptors and is a more important receptor modulation than plasma ANG II.

  12. Sodium intake, RAAS-blockade and progressive renal disease

    NARCIS (Netherlands)

    de Borst, Martin H; Navis, Gerjan

    2016-01-01

    Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the rena

  13. The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

    DEFF Research Database (Denmark)

    McMurray, John; Solomon, Scott; Pieper, Karen;

    2006-01-01

    OBJECTIVES: We attempted to compare the effect of an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) on atherosclerotic events. BACKGROUND: Angiotensin-converting enzyme inhibitors and ARBs interrupt the renin-angiotensin system by distinct mechanisms. It is n...

  14. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials

    DEFF Research Database (Denmark)

    Bangalore, Sripal; Kumar, Sunil; Kjeldsen, Sverre E;

    2011-01-01

    The risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs). We assessed the association between antihypertensive drugs and cancer risk in a comprehensive analysis of data from randomised clinical tr...

  15. Effectiveness of Angiotensin II Receptor Antagonists in a Cohort of Dutch Patients With Type 2 Diabetes Mellitus (ZODIAC-14)

    NARCIS (Netherlands)

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

    2015-01-01

    OBJECTIVE: There is limited evidence with respect to the between-group effects of various angiotensin receptor blockers (ARBs) on blood pressure and albuminuria in patients with type 2 diabetes mellitus. Therefore, we aimed to investigate the effects of differing ARBs on systolic blood pressure (SBP

  16. Olmesartan: Induced maculopapular rash

    Directory of Open Access Journals (Sweden)

    Aruna Bhushan

    2013-01-01

    Full Text Available Olmesartan medoxomil is an angiotensin receptor blocker (ARB which is shown to be effective and well tolerated in hypertensive patients. It is a frequently prescribed antihypertensive as it is considered safe. Here, we report the case of a patient who developed maculopapular rash during the course of the treatment with olmesartan medoxomil.

  17. Albuminuria and blood pressure, independent targets for cardioprotective therapy in patients with diabetes and nephropathy

    DEFF Research Database (Denmark)

    Holtkamp, Frank A; de Zeeuw, Dick; de Graeff, Pieter A

    2011-01-01

    The long-term cardioprotective effect of angiotensin receptor blockers (ARBs) is associated with the short-term lowering of its primary target blood pressure, but also with the lowering of albuminuria. Since the individual blood pressure and albuminuria response to an ARB varies between and withi...

  18. Effect of candesartan treatment on left ventricular remodeling after aortic valve replacement for aortic stenosis

    DEFF Research Database (Denmark)

    Dahl, Jordi S; Videbaek, Lars; Poulsen, Mikael K

    2010-01-01

    In hypertension, angiotensin receptor blockers can augment regression of left ventricular (LV) hypertrophy. It is not known whether this also is the case after aortic valve replacement (AVR) for severe aortic stenosis (AS). To test the hypothesis that treatment with candesartan in addition...

  19. New pharmacological strategies in chronic heart failure

    NARCIS (Netherlands)

    van de Wal, RMA; Voors, AA; Plokker, HWM; van Gilst, WH; van Veldhuisen, DJ

    2004-01-01

    Diuretics, ACE inhibitors and betablockers form the cornerstone of pharmacological treatment of chronic heart failure (CHF), while angiotensin receptor blockers are gaining ground. However, despite optimal treatment CHF remains a syndrome with poor prognosis. For this reason, a large number of new a

  20. Valsartan: the past, present and future

    DEFF Research Database (Denmark)

    Køber, Lars; Torp-Pedersen, Christian

    2005-01-01

    Valsartan (Diovan((R))) is a widely use angiotensin receptor blocker that prevents angiotensin II from binding to the subtype 1 receptor. Stimulation of the subtype 1 receptor is believed to mediate many of the deleterious effects accompanied by increased angiotensin II levels. Valsartan is effec...

  1. Irbesartan treatment does not influence plasma levels of the advanced glycation end products N(epsilon)(1-carboxymethyl)lysine and N(epsilon)(1-carboxyethyl)lysine in patients with type 2 diabetes and microalbuminuria. A randomized controlled trial

    DEFF Research Database (Denmark)

    Engelen, Lian; Persson, Frederik; Ferreira, Isabel;

    2011-01-01

    BACKGROUND: In vitro and animal experiments have shown inhibiting effects of angiotensin receptor blockers (ARBs) on the formation of advanced glycation end products (AGEs), which are known to be involved in the development of cardiovascular complications in diabetes. However, sufficient human data...

  2. Dual RAS Therapy Not on Target, but Fully Alive

    NARCIS (Netherlands)

    Lambers Heerspink, H. J.; de Zeeuw, D.

    2010-01-01

    Inhibitors of the renin-angiotensin system (RAS) form a cornerstone in the treatment of kidney disease. These drugs lower blood pressure and albuminuria, and afford renal protection. Dual therapy with an angiotensin-converting enzyme inhibitor and angiotensin receptor blocker have been shown to be m

  3. Increased serum potassium affects renal outcomes : a post hoc analysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial

    NARCIS (Netherlands)

    Miao, Y.; Dobre, D.; Lambers Heerspink, H. J.; Brenner, B. M.; Cooper, M. E.; Parving, H-H.; Shahinfar, S.; Grobbee, D.; de Zeeuw, D.

    2011-01-01

    To assess the effect of an angiotensin receptor blocker (ARB) on serum potassium and the effect of a serum potassium change on renal outcomes in patients with type 2 diabetes and nephropathy. We performed a post hoc analysis in patients with type 2 diabetes participating in the Reduction of Endpoint

  4. Efficacy and tolerability of a single-pill combination of telmisartan/hydrochlorothiazide 80/25 mg in Chinese and Korean patients with moderate to severe hypertension: a subgroup analysis of a randomized, double-blind, active-controlled trial

    Institute of Scientific and Technical Information of China (English)

    ZHU Ding-liang; GAO Ping-jin; LIU Shao-wen; Myung Ho Jeong; Michaela Mattheus; Birgit Voelker

    2013-01-01

    Background Hypertension is an important issue in Asia,responsible for up to 66% of cardiovascular disease cases.This randomized controlled trial subgroup analysis compared telmisartan 80 mg (T80)/hydrochlorothiazide 25 mg (H25) singlepill combination with T80 monotherapy,specifically in Chinese and Korean patients.Methods Patients with grade 2/3 hypertension were randomized to receive telmisartan 40 mg (T40)/hydrochlorothiazide 12.5 mg (H12.5) combination or T40 monotherapy for one week,before uptitrating the dose to T80/H25 or T80,respectively,for the remaining 6 weeks.The primary endpoint was systolic blood pressure (SBP) mean change from baseline.Secondary endpoints included mean diastolic blood pressure (DBP) change from baseline,and blood pressure (BP) goal achievement.Adverse events were recorded.Results Of a total 888 patients who were treated,efficacy analyses for Chinese and Korean patients included 127 patients treated with T80/H25 and 54 patients treated with T80.At week 7,mean SBP reductions from baseline were -37.5 mmHg (1 mmHg=0.133 kPa) and-26.9 mmHg in the T80/H25 and T80 groups (adjusted mean difference,-10.6 mmHg; 95% confidence interval (CO,-15.6 to-5.7).Mean DBP reductions were-19.0 and-14.1 mmHg in the T80/H25 and T80 groups (adjusted mean difference,-4.9 mmHg; 95% CI,-8.0 to-1.8).In total,56.7% of patients receiving T80/H25 achieved BP goal (<140/90 mmHg) compared with 35.2% receiving T80.SBP goal attainment (<140 mmHg) and DBP goal attainment (<90 mmHg) were also higher in the T80/H25 group compared with the T80 group (SBP:69.3% vs.48.1%; DBP:62.2% vs.46.3%).A small number of treatment-related adverse events were observed in both T80/H25 (nine patients,6.9%) and T80 monotherapy (two patients,3.6%) groups.Conclusions In Chinese and Korean patients with moderate-to-severe hypertension,treatment with T80/H25 provided large reductions in mean SBP and DBP,and high BP goal attainment rates.This once-daily combination is

  5. Telmisartan attrnuates ventilator-induced lung injury in rats%替米沙坦对大鼠呼吸机相关性肺损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    宋先斌; 肖军

    2012-01-01

    Objective To determine the effect of telmisartan on ventilator-induced lung injury ( VILI) in rats. Methods Forty healthy male SD rats were equally divided into four groups in random (A, B, C and D groups, n = 10). Group A served as control group, in which rats did not receive ventilation. Groups B, C and D received large-tide volume ventilation, but only rats from groups C and D received intraperitoneal injection with telmisartan solution (2. 5 and 5 mg/kg respectively. Telmisartan was dissolved in PBS) in 30 min before ventilation. Equal amount of PBS solution was given to rats in groups A and, B. A rat model of VILI was reproduced by volume-controlled mechanical ventilation with large tide volume ( Vt =40 ml/kg for 2 h) . Hemo-dynamic parameters and arterial blood gases of all the rats in the 4 groups were measured throughout the study period. After maintaining ventilation for 2 h, all rats were sacrificed and specimens of lung tissues and bron-choalveolar lavage fluid (BALF) were harvested. Lung pathological changes were observed by microscopy, and Smith score was estimated. The protein levels of peroxisome proliferator activated receptor-γ ( PPAR-γ) and Ang Ⅱ1 receptor (AT1R) in lung tissues were assayed with immunohistochemistry staining. Lung myeloperoxi-dase (MPO) activity and wet-dry weight ratio ( W/D) were measured. The levels of tumor necrosis factor-ot (TNF-α) and interleukin-8 (IL-8) in BALF were measured by enzyme-linked immunosorbent assay (ELISA). Results Mean Ph values in arterial blood from groups B, C and D tended to be higher than the base linevalue during the ventilation, while mean arterial pressure ( MAP) , mean partial pressure of carbon dioxide in arterial blood [ p ( C02) ] and mean partial pressure of oxygen in arterial blood [ p ( 02) ] were lower than baseline in these groups. MAP in groups C and D was significantly lower than in group B after 2 hours' ventilation( P < 0. 05 ). Smith score, mean MPO activity, mean W/D ratio

  6. Telmisartan Promotes Functional Activities of Endothelial Progenitor Cells via Activation of Phosphatei-Dylinositol-3-Kinase/Serine-Threonine Kinase%替米沙坦通过磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶途径改善内皮祖细胞的功能活性

    Institute of Scientific and Technical Information of China (English)

    曹政; 杨勇; 吴瑞霞; 陈彬; 华先平; 陈平英; 周选民

    2012-01-01

    Aim To investigate the functional effects of telmisartant on endothelial progenitor cells (EPC) functional activities. Methods Peripheral blood derived mononuclear cells containing EPC were isolated from healthy volunteers and then cultured on fibronectin-coated dishes with endothelial cell growth medium-2 ( EBM-2 ). The cells were cultured alone (control groups) ,with telmisartan (0.1 μmol/L, 1μmol/L, 10 μmol/L) , or telmisartan plus peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor( GW9662) or telmisartan plus PI3K-inhibitor(Ly294002). The proliferation, migration and adhesion activities of EPC were determined with MTT assay, transwell assay and adhesive assay, respectively. The expression of Akt and p-Akt were measured by Western Blot analysis. Results In the presence of telmisartan, numbers of colonies increased in a dose-dependent manner. Dil-ac-LDL uptake and lectin staining revealed that these proliferation colonies were EPC. The proliferative, migratory and adhesive activities of EPC were significantly enhanced after treated with telmisartan in a dose-dependent manner. The inhibition of PPARγ and Akt activa tion attenuated the effect of telmisartan on EPC functions. Meanwhile, the expression of p-Akt were significantly upregu-lated by the treatment of telmisartan. Conclusions Telmisartan could improve the proliferative, migratory and adhesive activities of EPC via the PDK/Akt pathway.of%目的 研究替米沙坦对内皮祖细胞增殖、迁移、黏附等生物学活性的影响并探讨其可能机制.方法 利用密度梯度离心法分离、培养人外周血单个核细胞,经FITC-UEA-I和Dil-acLDL双染色鉴定为正在分化的内皮祖细胞.将分离、培养的内皮祖细胞分为对照组、替米沙坦组(0.1 μmol/L、1μmol/L、10μmol/L)、过氧化体增殖物激活型受体γ抑制剂(GW9662)干预组和磷脂酰肌醇-3-羟基激酶抑制剂(Ly294002)干预组.采用MTT比色法、Transwell小室、细胞计数法

  7. Turbo Charge CPU Utilization in Fork/Join Using the ManagedBlocker

    CERN Document Server

    CERN. Geneva

    2017-01-01

    Fork/Join is a framework for parallelizing calculations using recursive decomposition, also called divide and conquer. These algorithms occasionally end up duplicating work, especially at the beginning of the run. We can reduce wasted CPU cycles by implementing a reserved caching scheme. Before a task starts its calculation, it tries to reserve an entry in the shared map. If it is successful, it immediately begins. If not, it blocks until the other thread has finished its calculation. Unfortunately this might result in a significant number of blocked threads, decreasing CPU utilization. In this talk we will demonstrate this issue and offer a solution in the form of the ManagedBlocker. Combined with the Fork/Join, it can keep parallelism at the desired level.

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

    Science.gov (United States)

    Doyle, Jefferson J; Doyle, Alexander J; Wilson, Nicole K; Habashi, Jennifer P; Bedja, Djahida; Whitworth, Ryan E; Lindsay, Mark E; Schoenhoff, Florian; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Ehsan, Hamid; Huso, David; Thomas, Craig J; Caulfield, Mark J; Van Eyk, Jennifer E; Judge, Daniel P; Dietz, Harry C

    2015-10-27

    Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.

  9. Antioxidant effect of T-type calcium channel blockers in gastric injury.

    Science.gov (United States)

    Bilici, Dilek; Banoğlu, Z Nur; Kiziltunç, Ahmet; Avci, Bahattin; Ciftçioğlu, Akif; Bilici, Sefa

    2002-04-01

    It is known that calcium ion has an important role in the cellular function. For this reason, calcium channel blockers may have a protective action against gastric injury which is induced by various stimuli. In this study, the influence of mibefradil on ethanol-induced gastric injury was investigated in rats. Mibefradil was given at a dose 50 mg/kg intraperitoneally 30 min before administration of 1 ml absolute ethanol given by gavage. We compared this effect of mibefradil with that of omeprazol. Ethanol-induced mucosal damage was evaluated using three different approaches: analysis of biochemical parameters and pathologic and macroscopic investigation. It was found that pretreatment with mibefradil significantly reduced ethanol-induced macroscopic, pathologic, and biochemical changes in the gastric mucosa. In conclusion, it is speculated that this findings may prove important in the development of new and improved therapies for the treatment and prevention of gastric ulcers in humans.

  10. Orgasm is preserved regardless of ejaculatory dysfunction with selective α1A-blocker administration

    Science.gov (United States)

    Kobayashi, K; Masumori, N; Kato, R; Hisasue, S; Furuya, R; Tsukamoto, T

    2009-01-01

    We evaluated whether ejaculatory dysfunction induced with a selective α1A-blocker influenced orgasm. Fifteen healthy male volunteers took silodosin or a placebo in a randomized, double-blind crossover design. We investigated the ejaculatory volume before and after administration of the agents. After each ejaculation, participants self-reported the answers to an original questionnaire, which was about discomfort on ejaculation, orgasm and satisfaction with the discomforting ejaculation. All participants on silodosin had a complete lack of seminal emission and expulsion. All participants felt orgasm in spite of a complete lack of seminal emission. Of the 15, 12 (80%) who had a somewhat uncomfortable feeling during orgasm were dissatisfied with this feeling, although 9 of the 12 reported that its degree was mild. Orgasm is preserved regardless of the loss of seminal emission with silodosin administration. Although most participants reported mild discomfort during orgasm, they were greatly dissatisfied with the loss of seminal emission. PMID:19536124

  11. Monte Carlo method for predicting of cardiac toxicity: hERG blocker compounds.

    Science.gov (United States)

    Gobbi, Marco; Beeg, Marten; Toropova, Mariya A; Toropov, Andrey A; Salmona, Mario

    2016-05-27

    The estimation of the cardiotoxicity of compounds is an important task for the drug discovery as well as for the risk assessment in ecological aspect. The experimental estimation of the above endpoint is complex and expensive. Hence, the theoretical computational methods are very attractive alternative of the direct experiment. A model for cardiac toxicity of 400 hERG blocker compounds (pIC50) is built up using the Monte Carlo method. Three different splits into the visible training set (in fact, the training set plus the calibration set) and invisible validation sets examined. The predictive potential is very good for all examined splits. The statistical characteristics for the external validation set are (i) the coefficient of determination r(2)=(0.90-0.93); and (ii) root-mean squared error s=(0.30-0.40).

  12. Use of clopidogrel and calcium channel blockers and risk of major adverse cardiovascular events

    DEFF Research Database (Denmark)

    Schmidt, Morten; Johansen, Martin B; Robertson, Douglas J

    2012-01-01

    Eur J Clin Invest 2011 ABSTRACT: Background  The CYP3A4 inhibition by calcium channel blockers (CCBs) may attenuate the effectiveness of clopidogrel. Using time-varying drug exposure ascertainment, we examined whether CCB use modified the association between clopidogrel use and major adverse......-month follow-up, we tracked the use of clopidogrel and CCBs and the rate of MACE (composite of myocardial infarction, ischaemic stroke, stent thrombosis, target lesion revascularization, or cardiac death). We used Cox regression to compute hazard ratios, controlling for potential confounders. Results......  Overall, the 12-month risk for MACE was 14·5%. The rate was 130 per 1000 person years for concomitant clopidogrel and CCB use, 106 for clopidogrel without CCB use, 213 for CCB without clopidogrel use, and 248 for no use of either drug. The adjusted hazard ratio for MACE comparing clopidogrel use...

  13. Angiotensin II receptor blocker-induced angioedema in the oral floor and epiglottis.

    Science.gov (United States)

    Shino, Masato; Takahashi, Katsumasa; Murata, Takaaki; Iida, Hideki; Yasuoka, Yoshihito; Furuya, Nobuhiko

    2011-01-01

    We report the rare case of angioedema (also known as Quincke edema), which was induced by valsartan, an angiotensin II receptor blocker (ARB). ARBs are a new class of antihypertensive agent that is developed to exclude the adverse effects of angiotensin-converting enzyme inhibitors. In theory, ARBs do not contribute to the occurrence of angioedema because they do not increase the serum level of bradykinin, the responsible substance for angioedema. However, some reports of ARB-induced angioedema have recently been published. In this study, we present the forth case and the first Asian case of angioedema due to valsartan, which is one of the ARBs. Otolaryngologist should be wary of the prescribing ARB and discontinue ARBs treatment soon, if angioedema is recognized.

  14. Effectiveness of beta-blocker therapy in daily practice patients with advanced chronic heart failure; is there an effect-modification by age?

    NARCIS (Netherlands)

    Dobre, D.; deJongste, M.J.L.; Lucas, C.; Cleuren, G.; van Veldhuisen, D.J.; Ranchor, A.V.; Haaijer-Ruskamp, F.

    2007-01-01

    Aims The effects of beta-blockers in daily practice patients with advanced chronic heart failure (CHF) and a broad range of ejection fraction (EF) are not well established. We aimed to assess, first, the association between beta-blocker prescription at discharge and mortality in a cohort of patients

  15. 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

    is presented to support the hypothesis that antihypertensive drugs that increase angiotensin II formation, such as diuretics, AT1-receptor blockers and dihydropyridines, may have greater brain anti-ischemic effects than antihypertensive drugs that decrease angiotensin II formation, such as beta-blockers...

  16. Efficiency, efficacy, and safety of EZ-blocker compared with left-sided double-lumen tube for one-lung ventilation

    NARCIS (Netherlands)

    Mourisse, J.M.; Liesveld, J.; Verhagen, A.F.T.M.; Rooij, G. van; Heide, S. van der; Schuurbiers, O.C.J.; Heijden, E. van der

    2013-01-01

    BACKGROUND: Double-lumen tubes (DLTs) or bronchial blockers are commonly used for one-lung ventilation. DLTs are sometimes difficult or even impossible to introduce, and the incidence of postoperative hoarseness and airway injuries is higher. Bronchial blockers are more difficult to position and nee

  17. A multiple ion channel blocker, NIP-142, for the treatment of atrial fibrillation.

    Science.gov (United States)

    Tanaka, Hikaru; Hashimoto, Norio

    2007-01-01

    Atrial fibrillation (AF) is one of the most frequent cardiac arrhythmia and is associated with increased cardiovascular morbidity and mortality, and the risk of stroke. Although currently available antiarrhythmic drugs are moderately effective in restoring normal sinus rhythm in patients with AF, excessive delay of ventricular repolarization by these agents may be associated with increased risk of proarrhythmia. Therefore, selective blockers of cardiac ion channel(s) that are exclusively present in the atria are highly desirable. NIP-142 is a novel benzopyrane derivative, which blocks potassium, calcium, and sodium channels and shows atrial specific action potential duration prolongation. NIP-142 preferentially blocks the ultrarapid delayed rectifier potassium current (I Kur) and the acetylcholine-activated potassium current (I KACh). Since I Kur and I KACh have been shown to be expressed more abundantly in the atrial than in the ventricular myocardium, the atrial-specific repolarization prolonging effect of NIP-142 is considered to be due to the blockade of these potassium currents. In canine models, NIP-142 was shown to terminate the microreentry type AF induced by vagal nerve stimulation and the macroreentry type atrial flutter induced by an intercaval crush. These effects of NIP-142 have been attributed to the prolongation of atrial effective refractory period (ERP), because this compound prolonged atrial ERP without affecting intraatrial and interatrial conduction times in these models. The ERP prolongation by NIP-142 was greater in the atrium than in the ventricle. NIP-142 also terminated the focal activity type AF induced by aconitine. In addition, NIP-142 reversed the atrial ERP shortening and the loss of rate adaptation induced by short-term rapid atrial pacing in anesthetized dogs. Thus, although clinical trials are required to provide evidence for its efficacy and safety, the novel multiple ion channel blocker, NIP-142, appears to be a useful agent for

  18. Removal of beta-blockers from aqueous media by adsorption onto graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Kyzas, George Z. [Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki (Greece); Koltsakidou, Anastasia [Laboratory of Environmental Pollution Control, Department of Chemistry, Aristotle University of Thessaloniki, GR–541 24 Thessaloniki (Greece); Nanaki, Stavroula G.; Bikiaris, Dimitrios N. [Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki (Greece); Lambropoulou, Dimitra A., E-mail: dlambro@chem.auth.gr [Laboratory of Environmental Pollution Control, Department of Chemistry, Aristotle University of Thessaloniki, GR–541 24 Thessaloniki (Greece)

    2015-12-15

    The aim of the present study is the evaluation of graphene oxide (GhO) as adsorbent material for the removal of beta-blockers (pharmaceutical compounds) in aqueous solutions. The composition and morphology of prepared materials were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). Atenolol (ATL) and propranolol (PRO) were used as model drug molecules and their behavior were investigated in terms of GhO dosage, contact time, temperature and pH. Adsorption mechanisms were proposed and the pH-effect curves after adsorption were discussed. The kinetic behavior of GhO-drugs system was analyzed after fitting to pseudo-first and -second order equations. The adsorption equilibrium data were fitted to Langmuir, Freundlich and Langmuir–Freundlich model calculating the maximum adsorption capacity (67 and 116 mg/g for PRO and ATL (25 °C), respectively). The temperature effect on adsorption was tested carrying out the equilibrium adsorption experiments at three different temperatures (25, 45, 65 °C). Then, the thermodynamic parameters of enthalpy, free energy and entropy were calculated. Finally, the desorption of drugs from GhO was evaluated by using both aqueous eluants (pH 2–10) and organic solvents. - Highlights: • Removal of beta-blockers by graphene oxide (GhO) from aqueous samples • Detailed adsorbent characterization and adsorption studies • Kinetic studies are performed and adsorption isotherms are determined and modeled. • GhO was proved to be an effective adsorbent for removal of atenolol and propranolol.

  19. The influence of selenium and deiodinases blockers on juvenile rats body weight

    Directory of Open Access Journals (Sweden)

    Milanović Svetlana

    2014-01-01

    Full Text Available In this work there was investigated the influence of selenium and deodinases blockers on juvenile rats body weight during three months. The experiment was carried out on 64 rats divided into eight groups with eight individual animals per group. Following groups were formed: 1. Se+PTU-IA- (control group, 2. Se+PTU+IA+, 3. Se+PTU+IA-, 4. Se+PTU- IA+, 5. Se-PTU-IA-, 6. Se-PTU+IA+, 7. Se-PTU+IA- and 8. Se-PTU-IA+. The groups labeled (Se+ were selenium adequate and they were fed with food that contained 0.334 mg Se/kg. The groups labeled (Se- were selenium deficient and obtained food with 0.031 mg Se/kg. As deiodinases blockers there were used propylthiouracil (PTU+ in a dose of 150 mg/L of drinking water and iopanoic acid (IA+ in a dose of 6 mg/100 g TM intraperitoneally. Body weight of experimental rats was measured every seven days. After three weeks of treatment there were taken blood samples of animals from all experimental groups and following parameters were determined: selenium concentration in blood, thyroxine (T4, triiodothyronine (T3 and thyroidstimulating hormone (TSH in blood plasma. Analysis of the samples showed that the animals from the groups treated with PTU had lower body weight in regard to the control group, as well as lower concentration of T3 and T4 in plasma. Selenium deficient rats had lower average body weight compared to the selenium adequate ones after three weeks, but there were no differences in thyroid hormones concentration. The lowest average body weight was noticed in selenium deficient rats groups treated with PTU. [Projekat Ministartsva nauke Republike Srbije, br. TR31050 i br. TR31003

  20. The omega-atracotoxins: selective blockers of insect M-LVA and HVA calcium channels.

    Science.gov (United States)

    Chong, Youmie; Hayes, Jessica L; Sollod, Brianna; Wen, Suping; Wilson, David T; Hains, Peter G; Hodgson, Wayne C; Broady, Kevin W; King, Glenn F; Nicholson, Graham M

    2007-08-15

    The omega-atracotoxins (omega-ACTX) are a family of arthropod-selective peptide neurotoxins from Australian funnel-web spider venoms (Hexathelidae: Atracinae) that are candidates for development as biopesticides. We isolated a 37-residue insect-selective neurotoxin, omega-ACTX-Ar1a, from the venom of the Sydney funnel-web spider Atrax robustus, with high homology to several previously characterized members of the omega-ACTX-1 family. The peptide induced potent excitatory symptoms, followed by flaccid paralysis leading to death, in acute toxicity tests in house crickets. Using isolated smooth and skeletal nerve-muscle preparations, the toxin was shown to lack overt vertebrate toxicity at concentrations up to 1 microM. To further characterize the target of the omega-ACTXs, voltage-clamp analysis using the whole-cell patch-clamp technique was undertaken using cockroach dorsal unpaired median neurons. It is shown here for the first time that omega-ACTX-Ar1a, and its homolog omega-ACTX-Hv1a from Hadronyche versuta, reversibly block both mid-low- (M-LVA) and high-voltage-activated (HVA) insect calcium channel (Ca(v)) currents. This block occurred in the absence of alterations in the voltage-dependence of Ca(v) channel activation, and was voltage-independent, suggesting that omega-ACTX-1 family toxins are pore blockers rather than gating modifiers. At a concentration of 1 microM omega-ACTX-Ar1a failed to significantly affect global K(v) channel currents. However, 1 microM omega-ACTX-Ar1a caused a modest 18% block of insect Na(v) channel currents, similar to the minor block of Na(v) channels reported for other insect Ca(v) channel blockers such as omega-agatoxin IVA. These findings validate both M-LVA and HVA Ca(v) channels as potential targets for insecticides.

  1. Effects of Calcium Channel Blockers on Antidepressant Action of Alprazolam and Imipramine

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2007-01-01

    Full Text Available Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group. One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine; two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil; four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups. Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect. This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

  2. Anion-Channel Blockers Inhibit S-Type Anion Channels and Abscisic Acid Responses in Guard Cells.

    Science.gov (United States)

    Schwartz, A.; Ilan, N.; Schwarz, M.; Scheaffer, J.; Assmann, S. M.; Schroeder, J. I.

    1995-10-01

    The effects of anion-channel blockers on light-mediated stomatal opening, on the potassium dependence of stomatal opening, on stomatal responses to abscisic acid (ABA), and on current through slow anion channels in the plasma membrane of guard cells were investigated. The anion-channel blockers anthracene-9-carboxylic acid (9-AC) and niflumic acid blocked current through slow anion channels of Vicia faba L. guard cells. Both 9-AC and niflumic acid reversed ABA inhibition of stomatal opening in V. faba L. and Commelina communis L. The anion-channel blocker probenecid also abolished ABA inhibition of stomatal opening in both species. Additional tests of 9-AC effects on stomatal aperture in Commelina revealed that application of this anion-channel blocker allowed wide stomatal opening under low (1 mM) KCI conditions and increased the rate of stomatal opening under both low and high (100 mM) KCI conditions. These results indicate that anion channels can function as a negative regulator of stomatal opening, presumably by allowing anion efflux and depolarization, which prohibits ion up-take in guard cells. Furthermore, 9-AC prevented ABA induction of stomatal closure. A model in which ABA activation of anion channels contributes a rate-limiting mechanism during ABA-induced stomatal closure and inhibition of stomatal opening is discussed.

  3. Beta-Blockers and Outcome in Heart Failure and Atrial Fibrillation A Meta-Analysis : a meta-analysis

    NARCIS (Netherlands)

    Rienstra, Michiel; Damman, Kevin; Mulder, Bart A.; Van Gelder, Isabelle C.; McMurray, John J. V.; Van Veldhuisen, Dirk J.

    2013-01-01

    Objectives The purpose of this study was to analyze the effect of beta blockade on outcome in patients with heart failure (HF) and atrial fibrillation (AF). Background Beta-blockers are widely used in patients with HF and AF. Recommendation in current HF guidelines, however, is based on populations

  4. Is heart rate reduction more important than target dose in chronic heart failure therapy with a beta-blocker?

    Institute of Scientific and Technical Information of China (English)

    Yong-Fang Guo; Yi An

    2011-01-01

    1 IntroductionBeta-adrenoceptor blocking agents (beta-blockers) are now well established as cornerstone therapy in patients with systolic chronic heart failure (CHF).[1] Clinical data have overwhelmingly proven the beneficial effects of beta-blocker therapy in terms of improving patient prognosis,decreasing requirements for hospitalization,and postponing disease progression.[2-4] However,it remains unclear what the optimal efficacious and safe dose for an individual patient with CHF is,and whether this can simply be inferred from the target dose for each beta-blocking agent as used in the major clinical trials.Beta-blockers are a heterogeneous class of drugs,and due to the polymorphisms of beta-adrenoceptor gene expression,there is marked individual variation in responsiveness to specific agents.[5] If pharmacodynamic markers of responsiveness to beta-blockade (such as heart rate (HR) reduction) are more important than the achievement of a target dose,could they become another potential therapeutic target in beta-blocker therapy? We provide a discussion of the question in this article.

  5. Coronary computed tomography angiography - Tolerability of β-blockers and contrast media, and temporal changes in radiation dose

    DEFF Research Database (Denmark)

    Pedersen, Charlotte; Thomsen, Camilla F; Hosbond, Susanne Elisabeth

    2014-01-01

    was compared with the exposure 3 years before. Results: There was no significant difference in the symptoms (dizziness, lipothymia and palpitations) between patients in and patients without β-blocker pre-treatment. Compared to baseline values, s-creatinine decreased non-significantly (75.2 versus 74.6 µmol...

  6. Efficacy of beta-blocker therapy in symptomatic athletes with exercise-induced intra-ventricular gradients

    Directory of Open Access Journals (Sweden)

    Cotrim Carlos

    2010-09-01

    Full Text Available Abstract Background Upright exercise stress echocardiography (SE induces significant intraventricular gradient (IVG and systolic anterior motion (SAM in a large proportion of symptomatic athletes, who may therefore benefit from a negative inotropic therapy. The purpose of the present study was to assess the effect of chronic oral β blocker therapy on the occurrence of exercise-induced IVG and mitral valve SAM, in symptomatic athletes. Methods We enrolled 35 symptomatic athletes (age = 23 ± 11 years with IVG (>30 mmHg during SE off therapy. All repeated SE on chronic oral beta-blocker therapy (atenolol up to 50 mg, bisoprolol up to 10 mg, or metoprolol up to 100 mg daily according to physician-driven choice. Results On therapy, there was during SE a reduction in IVG (35 off vs 17 on beta blocker, p Conclusions In athletes with positive screening on medical evaluation for sports practice and IVG on exertion, treatment with oral beta blockers improved symptoms in the large majority of patients. Symptomatic benefit was mirrored by objective evidence of improvement of echocardiographic signs of obstruction (IVG and SAM and reduction of ischemia-like electrocardiographic changes.

  7. Stroke Prevention: Not all Antihypertensive Drugs are Created Equal

    Directory of Open Access Journals (Sweden)

    Franz H Messerli

    2005-03-01

    Full Text Available Reductions in blood pressure (BP through intervention can significantly reduce the risk of cardiovascular events in hypertensive patients. However, a number of trials indicate that beta-blockers, despite lowering BP, do not reduce the risk of stroke.A recent meta-analysis suggested that, over and beyond BP reduction, angiotensin-converting enzyme (ACE inhibitors appear superior to calcium channel blockers for prevention of coronary heart disease whereas calcium channel blockers appear superior to ACE inhibitors for prevention of stroke.Indeed, in the Syst-EUR study a 42% reduction in strokes was achieved in the calcium antagonist arm when compared to the placebo arm.It is hypothesised that antihypertensive agents that stimulate the AT2-receptor (thiazide diuretics, dihydropyridine calcium antagonists and angiotensin receptor blockers are more cerebroprotective than drug classes that do not stimulate the AT2-receptor (beta-blockers and ACE inhibitors.The angiotensin receptor blockers are the only drug class that have a dual mechanism of action that could be helpful in preventing strokes in that they not only inhibit the AT1-receptor but also allow stimulation of the AT2-receptor. Not surprisingly therefore, in trials such as LIFE, VALUE and MOSES, angiotensin receptor blockers showed excellent cerebroprotection.

  8. SU-D-12A-07: Optimization of a Moving Blocker System for Cone-Beam Computed Tomography Scatter Correction

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, L; Yan, H; Jia, X; Jiang, S; Wang, J [UT Southwestern Medical Center, Dallas, TX (United States); Zhang, H [Southern Medical University, Guangzhou, Guang Dong (China)

    2014-06-01

    Purpose: A moving blocker based strategy has shown promising results for scatter correction in cone-beam computed tomography (CBCT). Different parameters of the system design affect its performance in scatter estimation and image reconstruction accuracy. The goal of this work is to optimize the geometric design of the moving block system. Methods: In the moving blocker system, a blocker consisting of lead strips is inserted between the x-ray source and imaging object and moving back and forth along rotation axis during CBCT acquisition. CT image of an anthropomorphic pelvic phantom was used in the simulation study. Scatter signal was simulated by Monte Carlo calculation with various combinations of the lead strip width and the gap between neighboring lead strips, ranging from 4 mm to 80 mm (projected at the detector plane). Scatter signal in the unblocked region was estimated by cubic B-spline interpolation from the blocked region. Scatter estimation accuracy was quantified as relative root mean squared error by comparing the interpolated scatter to the Monte Carlo simulated scatter. CBCT was reconstructed by total variation minimization from the unblocked region, under various combinations of the lead strip width and gap. Reconstruction accuracy in each condition is quantified by CT number error as comparing to a CBCT reconstructed from unblocked full projection data. Results: Scatter estimation error varied from 0.5% to 2.6% as the lead strip width and the gap varied from 4mm to 80mm. CT number error in the reconstructed CBCT images varied from 12 to 44. Highest reconstruction accuracy is achieved when the blocker lead strip width is 8 mm and the gap is 48 mm. Conclusions: Accurate scatter estimation can be achieved in large range of combinations of lead strip width and gap. However, image reconstruction accuracy is greatly affected by the geometry design of the blocker.

  9. The period between beta-blocker use and physical activity changes training heart rate behavior

    Directory of Open Access Journals (Sweden)

    Naiane Ferraz Bandeira Alves

    2009-12-01

    Full Text Available The Brazilian Society of Cardiology (SBC proposes that hypertensive subjects who use beta-blockers and practice physical exercises must have their training heart rate (HR corrected due to the negative chronotropic effect of this drug. Nevertheless, if the physical activity is performed outside of plasmatic half-life, correction may not be necessary. This study investigated the exercise chronotropic response both inside and outside the beta-blocker plasmatic half-life. Nine subjects in use of atenolol or propranolol, and six controls, carried out three walking sessions in three days according to different schedules: EX2 (two hours after drug administration, at the plasmatic peak; EX11 (eleven hours after drug administration, at the end of plasmatic half-life; and EX23 (twenty-three hours after drug administration, outside the plasmatic half-life. The walking sessions were performed on an ergometric treadmill and HR was monitored by a heart rate monitor. During the exercises, mean HRs were 97.2, 108.4 and 109 for EX2, EX11 and EX23, respectively, with the value for EX2 statistically lower than the others (p0.05. The study concludes that the attenuation of the positive chronotropic response which occurs during exercise in subjects using beta-blockers, is less evident when the exercise is performed outside the plasmatic half-life of the drug.A Sociedade Brasileira de Cardiologia (SBC propõe que os hipertensos que utilizam beta-bloqueadores e praticam exercícios físicos devem ter sua frequência cardíaca de treinamento (HR corrigida devido ao efeito cronotrópico negativo desse fármaco. Contudo, se a atividade física é realizada fora da meia-vida plasmática do fármaco, a correção pode não ser necessária. Este estudo investigou a resposta cronotrópica ao exercício dentro e fora da meia-vida plasmática do beta-bloqueador. Nove indivíduos que usavam atenolol ou propranolol e seis controles, efetuaram três sessões de caminhada em tr

  10. Powdermill Nursing Home & Care Centre, Gunpowdermills, Ballincollig, Cork.

    LENUS (Irish Health Repository)

    Coveney, A P

    2011-03-01

    To examine the current medical management of arteriopathic patients attending a vascular surgical service at a university teaching hospital over a 6-month period. The prescribing of antiplatelets, statins, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers and beta-blockers was specifically examined. Vascular patients are often under the care of multiple specialties, and therefore the influence of different medical specialties on the patients\\' medical management was also examined.

  11. Lipid Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008393 Effects of angiotensin Ⅱ type 1 receptor blocker on triglyceride metabolism in the liver: experiment with Zucker fatty rats. RAN Jianmin(冉建民), et al. Dept Endocrinol, Guangzhou Red Cross Hosp, 4th Hosp Med Coll, Jinan Univ, Guangzhou 510220. Natl Med J China 2008;88(22):1557-1561. Objective To investigate the effects of angiotensin receptor blocker (ARB) on triglyceride (TG) metabolism and mechanism thereof.

  12. ACE up the sleeve - are vascular patients medically optimized?

    LENUS (Irish Health Repository)

    Coveney, A P

    2011-03-01

    To examine the current medical management of arteriopathic patients attending a vascular surgical service at a university teaching hospital over a 6-month period. The prescribing of antiplatelets, statins, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers and beta-blockers was specifically examined. Vascular patients are often under the care of multiple specialties, and therefore the influence of different medical specialties on the patients\\' medical management was also examined.

  13. 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.

  14. Impact of β-blocker selectivity on long-term outcomes in congestive heart failure patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Kubota Y

    2015-03-01

    Full Text Available Yoshiaki Kubota, Kuniya Asai, Erito Furuse, Shunichi Nakamura, Koji Murai, Yayoi Tetsuou Tsukada, Wataru Shimizu Department of Medicine (Division of Cardiology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan Background: Chronic obstructive pulmonary disease (COPD is present in approximately one-third of all congestive heart failure (CHF patients, and is a key cause of underprescription and underdosing of β-blockers, largely owing to concerns about precipitating respiratory deterioration. For these reasons, the aim of this study was to evaluate the impact of β-blockers on the long-term outcomes in CHF patients with COPD. In addition, we compared the effects of two different β-blockers, carvedilol and bisoprolol. Methods: The study was a retrospective, non-randomized, single center trial. Acute decompensated HF patients with COPD were classified according to the oral drug used at discharge into β-blocker (n=86; carvedilol [n=52] or bisoprolol [n=34] and non-β-blocker groups (n=46. The primary endpoint was all-cause mortality between the β-blocker and non-β-blocker groups during a mean clinical follow-up of 33.9 months. The secondary endpoints were the differences in all-cause mortality and the hospitalization rates for CHF and/or COPD exacerbation between patients receiving carvedilol and bisoprolol. Results: The mortality rate was higher in patients without β-blockers compared with those taking β-blockers (log-rank P=0.039, and univariate analyses revealed that the use of β-blockers was the only factor significantly correlated with the mortality rate (hazard ratio: 0.41; 95% confidence interval: 0.17–0.99; P=0.047. Moreover, the rate of CHF and/or COPD exacerbation was higher in patients treated with carvedilol compared with bisoprolol (log-rank P=0.033. In the multivariate analysis, only a past history of COPD exacerbation significantly increased the risk of re-hospitalization due to CHF and/or COPD exacerbation (adjusted hazard

  15. Anti-aging effect of simvastatin and telmisartan on retinas and its mechanism in rats%辛伐他汀和替米沙坦对大鼠视网膜衰老的延缓作用及其机制

    Institute of Scientific and Technical Information of China (English)

    王静; 康前雁

    2016-01-01

    Background Statins has prominent roles in regulating lipids,anti-inflammation,autoxidation and protecting vascular endothelial cells.Sartans can promote cell growth and the expression of cytokines.Since the pleiotropic effects of statins and sartans on a variety of cell types,it is inferred that the two medicines can delay retinal aging.Objective This study was to explore the anti-aging effect of simvastatin and telmisartan on the physiological aging of retina.Methods Sixty-six three-month-old healthy SD rats were selected in this study,and 6 of them served as the youth group and the right eyeballs were immediately enucleated.The other rats were raised until 9-month-old in the same conditions and then randomly divided into the simvastatin group,telmisartan group and the control group with 20 rats for each group.The simvastatin of 5 mg/kg and telmisartan of 8 mg/kg were given by intragastric administration once a day in the simvastatin group and the telmisartan group until 17-month-old,and the equal amount of normal saline was used in the control group in the same way.The number of survival rats was 12 in the simvastatin group,10 in the telmisartan group and 8 in the control group.The right eyes were enucleated after heart perfusion of 4% paraformaldehyde solution for the preparation of retinal paraffin sections.Retinal thickness was measured by pathological examination,and the expressions of the retinal neuron markers,including Thy-1,protein kinase C-α (PKC-ot),opsin and rhodopsin,were detected by immunofluorescence technique to evaluate the morphology of retinal ganglion cells (RGCs),bipolar cells as well as the thickness of the outer segment of photoreceptors.Results The retinal structure was clear in the rats of the youth group.However,the RGCs arrangement and inner segment (IS) and outer segment (OS) structure were abnormal in the simvastatin group,the telmisartan group and the control group.Compared with the rats of the youth group,the thickness of outer

  16. Cl- channel blockers NPPB and niflumic acid blunt Ca(2+)-induced erythrocyte 'apoptosis'.

    Science.gov (United States)

    Myssina, Svetlana; Lang, Philipp A; Kempe, Daniela S; Kaiser, Stefanie; Huber, Stephan M; Wieder, Thomas; Lang, Florian

    2004-01-01

    Exposure to Ca2+ ionophore ionomycin, osmotic shock, oxidative stress and glucose depletion trigger cell shrinkage and scramblase-mediated phosphatidylserine exposure at the outer leaflet of the erythrocyte cell membrane. The effects are partially due to activation of GARDOS channels and subsequent cellular K+ loss leading not only to cell shrinkage but also participating in the triggering of erythrocyte scramblase. As conductive loss of K+ would depend on the parallel loss of anions we hypothesised that activation of scramblase is similarly dependent on the activity of Cl- channels. To test this hypothesis, we used Cl- channel blockers NPPB and niflumic acid. It is shown here that treatment of erythrocytes with 1 microM ionomycin leads to cellular K+ loss, decrease of hematocrit and decrease of forward scatter in FACS analysis reflecting cell shrinkage as well as increase of annexin positive cells reflecting phosphatidylserine exposure. Those events were significantly blunted in the presence of 100 microM NPPB by 34% (K+ loss), 45% (hematocrit), 32% (forward scatter) and 69% (annexin binding), or in the presence of 100 microM niflumic acid by 15% (forward scatter) and 45% (annexin binding), respectively. Moreover, oxidative stress triggered annexin binding which was again significantly inhibited (by 51%) in the presence of 100 microM NPPB. In conclusion, Cl- channels presumably participate in the regulation of erythrocyte 'apoptosis'.

  17. 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.

  18. Degradation kinetics and pathways of three calcium channel blockers under UV irradiation.

    Science.gov (United States)

    Zhu, Bing; Zonja, Bozo; Gonzalez, Oscar; Sans, Carme; Pérez, Sandra; Barceló, Damia; Esplugas, Santiago; Xu, Ke; Qiang, Zhimin

    2015-12-01

    Calcium channel blockers (CCBs) are a group of pharmaceuticals widely prescribed to lower blood pressure and treat heart diseases. They have been frequently detected in wastewater treatment plant (WWTP) effluents and downstream river waters, thus inducing a potential risk to aquatic ecosystems. However, little is known about the behavior and fate of CCBs under UV irradiation, which has been adopted as a primary disinfection method for WWTP effluents. This study investigated the degradation kinetics and pathways of three commonly-used CCBs, including amlodipine (AML), diltiazem (DIL), and verapamil (VER), under UV (254 nm) irradiation. The chemical structures of transformation byproducts (TBPs) were first identified to assess the potential ecological hazards. On that basis, a generic solid-phase extraction method, which simultaneously used four different cartridges, was adopted to extract and enrich the TBPs. Thereafter, the photo-degradation of target CCBs was performed under UV fluences typical for WWTP effluent disinfection. The degradation of all three CCBs conformed to the pseudo-first-order kinetics, with rate constants of 0.031, 0.044 and 0.011 min(-1) for AML, DIL and VER, respectively. By comparing the MS(2) fragments and the evolution (i.e., formation or decay) trends of identified TBPs, the degradation pathways were proposed. In the WWTP effluent, although the target CCBs could be degraded, several TBPs still contained the functional pharmacophores and reached peak concentrations under UV fluences of 40-100 mJ cm(-2).

  19. Protonated form: the potent form of potassium-competitive acid blockers.

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    Hua-Jun Luo

    Full Text Available Potassium-competitive acid blockers (P-CABs are highly safe and active drugs targeting H+,K+-ATPase to cure acid-related gastric diseases. In this study, we for the first time investigate the interaction mechanism between the protonated form of P-CABs and human H+,K+-ATPase using homology modeling, molecular docking, molecular dynamics and binding free energy calculation methods. The results explain why P-CABs have higher activities with higher pKa values or at lower pH. With positive charge, the protonated forms of P-CABs have more competitive advantage to block potassium ion into luminal channel and to bind with H+,K+-ATPase via electrostatic interactions. The binding affinity of the protonated form is more favorable than that of the neutral P-CABs. In particular, Asp139 should be a very important binding site for the protonated form of P-CABs through hydrogen bonds and electrostatic interactions. These findings could promote the rational design of novel P-CABs.

  20. Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

    Science.gov (United States)

    Liu, Shuyuan; Yue, Longtao; Gu, Wenrui; Li, Xiuyun; Zhang, Liuping; Sun, Shujuan

    2016-01-01

    Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers), amlodipine (AML), nifedipine (NIF), benidipine (BEN) and flunarizine (FNZ) with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1) expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI) fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin) and YVC1 (encoding calcium channel protein in vacuole membrane).

  1. Removal of beta-blockers from aqueous media by adsorption onto graphene oxide.

    Science.gov (United States)

    Kyzas, George Z; Koltsakidou, Anastasia; Nanaki, Stavroula G; Bikiaris, Dimitrios N; Lambropoulou, Dimitra A

    2015-12-15

    The aim of the present study is the evaluation of graphene oxide (GhO) as adsorbent material for the removal of beta-blockers (pharmaceutical compounds) in aqueous solutions. The composition and morphology of prepared materials were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). Atenolol (ATL) and propranolol (PRO) were used as model drug molecules and their behavior were investigated in terms of GhO dosage, contact time, temperature and pH. Adsorption mechanisms were proposed and the pH-effect curves after adsorption were discussed. The kinetic behavior of GhO-drugs system was analyzed after fitting to pseudo-first and -second order equations. The adsorption equilibrium data were fitted to Langmuir, Freundlich and Langmuir-Freundlich model calculating the maximum adsorption capacity (67 and 116 mg/g for PRO and ATL (25 °C), respectively). The temperature effect on adsorption was tested carrying out the equilibrium adsorption experiments at three different temperatures (25, 45, 65 °C). Then, the thermodynamic parameters of enthalpy, free energy and entropy were calculated. Finally, the desorption of drugs from GhO was evaluated by using both aqueous eluants (pH2-10) and organic solvents.

  2. Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

    Directory of Open Access Journals (Sweden)

    Shuyuan Liu

    Full Text Available Candidiasis has increased significantly recently that threatens patients with low immunity. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of fungal resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapy is one of the most widely used and effective strategy to alleviate this problem. In this paper, we were aimed to evaluate the combined antifungal effects of four CCBs (calcium channel blockers, amlodipine (AML, nifedipine (NIF, benidipine (BEN and flunarizine (FNZ with fluconazole against C. albicans by checkerboard and time-killing method. In addition, we determined gene (CCH1, MID1, CNA1, CNB1, YVC1, CDR1, CDR2 and MDR1 expression by quantitative PCR and investigated the efflux pump activity of resistant candida albicans by rhodamine 6G assay to reveal the potential mechanisms. Finally, we concluded that there was a synergy when fluconazole combined with the four tested CCBs against resistant strains, with fractional inhibitory concentration index (FICI <0.5, but no interaction against sensitive strains (FICI = 0.56 ~ 2. The mechanism studies revealed that fluconazole plus amlodipine caused down-regulating of CNA1, CNB1 (encoding calcineurin and YVC1 (encoding calcium channel protein in vacuole membrane.

  3. Efficacy and safety of calcium channel blockers in hypertensive patients with concomitant left ventricular dysfunction.

    Science.gov (United States)

    Parmley, W W

    1992-04-01

    The use of calcium channel blockers (CCBs) in the treatment of hypertension and concomitant left ventricular dysfunction is reviewed. Some CCBs, particularly second-generation dihydropyridine agents such as felodipine, isradipine, nicardipine, nimodipine, and nitrendipine, have properties that enhance their usefulness in these patients. All CCBs have a similar mechanism of action. Differences in their selective action at various tissue sites determine which are most appropriate for patients with concomitant hypertension and left ventricular dysfunction. Most CCBs do not produce reflex stimulation of the heart or induce intravascular expansion. While all CCBs produce arteriolar dilation, all local beds and regional circulations in target organs are not affected equally. Most CCBs can decrease cardiac mass, and second-generation CCBs tend to have little or no negative inotropic effects at therapeutic dosages. In addition, they increase blood flow and reduce myocardial oxygen requirements. Because of differences in functional and electrophysiologic effects, specific CCBs may not be appropriate for all patients. Since second-generation dihydropyridine CCBs lack clinically relevant negative inotropic effects, and have been shown to improve exercise tolerance and coronary artery perfusion, they are appropriate for hypertensive patients with left ventricular dysfunction, angina, and coronary heart disease. Second-generation CCBs tend to lack cardiodepressant side effects and are less likely to react with digoxin than are first-generation CCBs.

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

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    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.

  5. Topically Applied Hsp90 Blocker 17AAG Inhibits Autoantibody-Mediated Blister-Inducing Cutaneous Inflammation.

    Science.gov (United States)

    Tukaj, Stefan; Bieber, Katja; Kleszczyński, Konrad; Witte, Mareike; Cames, Rebecca; Kalies, Kathrin; Zillikens, Detlef; Ludwig, Ralf J; Fischer, Tobias W; Kasperkiewicz, Michael

    2017-02-01

    Cell stress-inducible Hsp90 has been recognized as key player in mediating inflammatory responses. Although its systemic blockade was successfully used to treat autoimmune diseases in preclinical models, efficacy of a topical route of Hsp90 inhibitor administration has so far not been evaluated in chronic inflammatory and autoimmune-mediated dermatoses. Here, effects of the Hsp90 blocker 17-allylamino-demethoxygeldanamycin (17AAG) applied topically to the skin were determined in experimental inflammatory epidermolysis bullosa acquisita (EBA), an anti-type VII collagen autoantibody-induced blistering skin disease. Topical 17AAG ameliorated clinical disease severity when given before or during the occurrence of skin lesions without causing cutaneous or systemic toxicity in mice with antibody transfer- and immunization-induced EBA. In both EBA models and in the setting of locally induced inflammation, topical 17AAG treatment was associated with (i) reduced neutrophilic infiltrates, (ii) decreased NF-κB activation, (iii) lowered expression of matrix metalloproteinases and Flii, and (iv) induction of anti-inflammatory Hsp70 in the skin. Our results suggest that topical delivery of Hsp90 antagonists, offering the benefit of a reduced risk of systemic adverse effects of Hsp90 inhibition, may be useful for the control of EBA and possibly other related inflammatory skin disorders.

  6. Neuroprotection in the treatment of glaucoma--A focus on connexin43 gap junction channel blockers.

    Science.gov (United States)

    Chen, Ying-Shan; Green, Colin R; Danesh-Meyer, Helen V; Rupenthal, Ilva D

    2015-09-01

    Glaucoma is a form of optic neuropathy and a common cause of blindness, affecting over 60 million people worldwide with an expected rise to 80 million by 2020. Successful treatment is challenging due to the various causes of glaucoma, undetectable symptoms at an early stage and inefficient delivery of drugs to the back of the eye. Conventional glaucoma treatments focus on the reduction of elevated intraocular pressure (IOP) using topical eye drops. However, their efficacy is limited to patients who suffer from high IOP glaucoma and do not address the underlying susceptibility of retinal ganglion cells (RGC) to degeneration. Glaucoma is known as a neurodegenerative disease which starts with RGC death and eventually results in damage of the optic nerve. Neuroprotective strategies therefore offer a novel treatment option for glaucoma by not only preventing neuronal loss but also disease progression. This review firstly gives an overview of the pathophysiology of glaucoma as well as current treatment options including conventional and novel delivery strategies. It then summarizes the rational for neuroprotection as a novel therapy for glaucomatous neuropathies and reviews current potential neuroprotective strategies to preserve RGC, with a focus on connexin43 (Cx43) gap junction channel blockers.

  7. Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization.

    Science.gov (United States)

    Lee, Hyang-Ae; Hyun, Sung-Ae; Park, Sung-Gurl; Kim, Ki-Suk; Kim, Sung Joon

    2016-01-01

    Dihydropyridine (DHP) calcium channel blockers (CCBs) have been widely used to treat of several cardiovascular diseases. An excessive shortening of action potential duration (APD) due to the reduction of Ca(2+) channel current (I Ca) might increase the risk of arrhythmia. In this study we investigated the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on the cardiac APD in rabbit Purkinje fibers, voltage-gated K(+) channel currents (I Kr, I Ks) and voltage-gated Na(+) channel current (I Na). The concentration-dependent inhibition of Ca(2+) channel currents (I Ca) was examined in rat cardiomyocytes; these CCBs have similar potency on I Ca channel blocking with IC50 (the half-maximum inhibiting concentration) values of 0.142, 0.229, and 0.227 nM on NIC, ISR, and AML, respectively. However, ISR shortened both APD50 and APD90 already at 1 µM whereas NIC and AML shortened APD50 but not APD90 up to 30 µM. According to ion channel studies, NIC and AML concentration-dependently inhibited I Kr and I Ks while ISR had only partial inhibitory effects (NIC and AML could compensate for the AP shortening effects due to the block of I Ca.

  8. A comparative ex vivo drug permeation study of beta-blockers through porcine buccal mucosa.

    Science.gov (United States)

    Amores, Sonia; Lauroba, Jacinto; Calpena, Ana; Colom, Helena; Gimeno, Alvaro; Domenech, José

    2014-07-01

    Apparent permeability coefficients (kp) of a series of beta-blockers: acebutolol, atenolol, labetalol, metoprolol, oxprenolol and propranolol, through porcine buccal mucosa were determined. The aim of the study was to determine the permeation parameters (apparent permeability coefficient, kp; flux, J; and lag time, TL) as a measure of the intrinsic permeability of porcine buccal mucosa to these drugs, in order to predict the efficacy of their possible administration through human buccal mucosa. A positive linear correlation was observed between the apparent permeability coefficient, kpand the partition coefficient, P. Oxprenolol and propranolol are the drugs that presented the highest values of kp: 0.3231×10(2) cm/h and 0.5666×10(2) cm/h, respectively. Multiple linear regression (MLR) using least square estimation was performed on the data set with logkpas dependent variable and the descriptors as predictor variables. The potential systemic capacity after a buccal administration was predicted by estimating the plasma concentrations at steady-stated (Css). Considering the entire process of permeation ex vivo, propranolol and oxprenolol would seem to be the best candidates for administration through the buccal mucosa.

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

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    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.

  10. Straightforward approach to produce recombinant scorpion toxins-Pore blockers of potassium channels.

    Science.gov (United States)

    Nekrasova, Oksana; Kudryashova, Ksenia; Fradkov, Arkadiy; Yakimov, Sergey; Savelieva, Maria; Kirpichnikov, Mikhail; Feofanov, Alexey

    2017-01-10

    Scorpion venom peptide blockers (KTx) of potassium channels are a valuable tool for structure-functional studies and prospective candidates for medical applications. Low yields of recombinant KTx hamper their wide application. We developed convenient and efficient bioengineering approach to a large-scale KTx production that meets increasing demands for such peptides. Maltose-binding protein was used as a carrier for cytoplasmic expression of folded disulfide-rich KTx in E. coli. TEV protease was applied for in vitro cleavage of the target peptide from the carrier. To produce KTx with retained native N-terminal sequence, the last residue of TEV protease cleavage site (CSTEV) was occupied by the native N-terminal residue of a target peptide. It was shown that decreased efficiency of hydrolysis of fusion proteins with non-canonical CSTEV can be overcome without by-product formation. Disulfide formation and folding of a target peptide occurred in cytoplasm eliminating the need for renaturation procedure in vitro. Advantages of this approach were demonstrated by producing six peptides with three disulfide bonds related to four KTx sub-families and achieving peptide yields of 12-22mg per liter of culture. The developed approach can be of general use for low-cost production of various KTx, as well as other disulfide-rich peptides and proteins.

  11. Management of Agitation Following Aneurysmal Subarachnoid Hemorrhage: Is There a Role for Beta-Blockers?

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    Fayaz Ibrahim

    2012-01-01

    Full Text Available Introduction. Stroke is a leading cause of mortality and morbidity in the United States. About 20% of the stroke is hemorrhagic and about 50% of these is due to aneurysmal subarachnoid hemorrhage. A troublesome neuropsychiatric complication of subarachnoid hemorrhage is agitation/aggression. Case Presentation. A 45-year-old man with no prior psychiatric history, sustained subarachnoid hemorrhage. After initial stabilization for 2 days, he underwent craniotomy and clipping of anterior cerebral communicating artery aneurysm. Treatment was continued with labetalol, nimodipine, and levetiracetam. Beginning postoperative day 4, patient developed episodes of confusion and agitation/aggression. Switching of Levetiracetam to valproate did not show any improvement. Psychiatry team tried to manage him with intense nursing intervention and different medications like olanzapine, valproate, lorazepam, and haloperidol. However, patient continued to be agitated and aggressive. Switching from labetalol to metoprolol resulted in dramatic improvement within 3 days. Discussion. Antipsychotics and benzodiazepines are often not sufficiently effective in the control of agitation/aggression in patients with traumatic brain injury and similar conditions. Our case report and the literature review including a cochrane review suggests that beta-blockers may be helpful in this situation.

  12. Patient medication adherence and physician prescribing among congestive heart failure patients of Yemen

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    K M Alakhali

    2013-01-01

    Full Text Available Congestive heart failure has been associated with high morbidity and mortality requiring hospitalisation and is further complicated by noncompliance and under prescriptions. We aim to determine medication adherence and percentage deviation among Asians population in general and Yemenis in particular. A cross-sectional, prospective observational study with purposive sampling was conducted at two cardiac outpatient centers in 70 congestive heart failure patients for a period of 3 months. An Arabic translated Morisky 4 item scale assessed the adherence of patients. Deviation in prescribing was determined by chart review. All 70 patients had mean age of 56.6΁16 years. Morisky 4 item scale predicted low adherence (n=33; 47.1% and overall nonadherencerate (n=38; 54.2% was slightly higher than adherence. Percentage nonadherence versus adherence was high with diuretics (53 vs. 46% and, digoxin (40 vs. 29%. The adherence percentage of angiotensin receptor blockers (9% and beta blockers (8% was low. Diuretics were the most prescribed drugs (n=69; 99%, followed by angiotensin converting enzyme inhibitors (n=51; 73%, cardiac glycoside (n=48; 69%, few patients were on angiotensin receptor blockers (n=8; 11% and (n=9; 13% beta blockers. The maximum prescribing rate deviation was seen with angiotensin receptor blockers (−89% and beta blockers (−87% followed by nitrates (−77%. Digoxin (−31% and angiotensin converting enzymes (−27% deviated comparatively less. Prescribing as well as utilisation rates generally were low resulting in nonachievement of therapeutic goals which could be resolved using multimodel approach.

  13. Patient Medication Adherence and Physician Prescribing among Congestive Heart Failure Patients of Yemen

    Science.gov (United States)

    Alakhali, K. M.; Daniel, P. S; Noohu, A. M.; Sirajudeen, S. A.

    2013-01-01

    Congestive heart failure has been associated with high morbidity and mortality requiring hospitalisation and is further complicated by noncompliance and under prescriptions. We aim to determine medication adherence and percentage deviation among Asians population in general and Yemenis in particular. A cross-sectional, prospective observational study with purposive sampling was conducted at two cardiac outpatient centers in 70 congestive heart failure patients for a period of 3 months. An Arabic translated Morisky 4 item scale assessed the adherence of patients. Deviation in prescribing was determined by chart review. All 70 patients had mean age of 56.6±16 years. Morisky 4 item scale predicted low adherence (n=33; 47.1%) and overall nonadherencerate (n=38; 54.2%) was slightly higher than adherence. Percentage nonadherence versus adherence was high with diuretics (53 vs. 46%) and, digoxin (40 vs. 29%). The adherence percentage of angiotensin receptor blockers (9%) and beta blockers (8%) was low. Diuretics were the most prescribed drugs (n=69; 99%), followed by angiotensin converting enzyme inhibitors (n=51; 73%), cardiac glycoside (n=48; 69%), few patients were on angiotensin receptor blockers (n=8; 11%) and (n=9; 13%) beta blockers. The maximum prescribing rate deviation was seen with angiotensin receptor blockers (−89%) and beta blockers (−87%) followed by nitrates (−77%). Digoxin (−31%) and angiotensin converting enzymes (−27%) deviated comparatively less. Prescribing as well as utilisation rates generally were low resulting in nonachievement of therapeutic goals which could be resolved using multimodel approach. PMID:24403656

  14. 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...

  15. "Oral ascorbic acid in combination with beta blockers in prevention of atrial fibrillation after Coronary Artery Bypass Graft "

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    Mousavi M

    2007-04-01

    Full Text Available Background: Adrenergic beta antagonists are not sufficient to prevent atrial fibrillation after coronary artery bypass graft (CABG. This study was designed to evaluate the effect of ascorbic acid as an adjunct to beta-blockers in prevention of post-CABG atrial fibrillation Methods: Patients who were more than 50 years old and scheduled to undergo CABG were included if they were treated with beta-blockers at least 1 week before surgery. Patients with previous history of atrial fibrillation, AV block, heart rate <50 /min, end-stage renal disease, severe pulmonary or liver disease and those who were taking digoxin or class I and III anti-arrhythmics or had pacemakers were not included. Ascorbic acid group were prescribed 2 gm of ascorbic acid, the night before the surgery, and 1 gm twice daily for 5 days after surgery. Beta blockers continued in both group after surgery. Telemetry monitoring was performed in ICU and Holter monitoring was performed for 4 days. Results: Fifty patients completed the study as ascorbic acid and 50 as control group. The population was 60.19 ± 7.14 years old and 67% were male. The incidence of postoperative atrial fibrillation was 4% in the ascorbic acid group and 26% in control group (odds ratio=0.119, 95% confidence interval: 0.025 to 0.558, P=0.002 Conclusion: Ascorbic acid is well-tolerated, relatively safe and seems effective. Therefore it can be prescribed as an adjunct to beta-blockers for prophylaxis of post-CABG atrial fibrillation.

  16. β1-blockers lower norepinephrine release by inhibiting presynaptic, facilitating β1-adrenoceptors in normotensive and hypertensive rats

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    Torill eBerg

    2014-04-01

    Full Text Available Peripheral norepinephrine release is facilitated by presynaptic β-adrenoceptors (AR, believed to involve the β2-subtype exclusively. However, β1-selective blockers are the most commonly used β-blockers in hypertension. Here I tested the hypothesis that β1AR may function as presynaptic, release-facilitating auto-receptors. Since β1AR-blockers are injected during myocardial infarction, their influence on the cardiovascular response to acute norepinephrine release was also studied. By a newly established method, using tyramine-stimulated release through the norepinephrine transporter (NET, presynaptic control of catecholamine release was studied in normotensive and spontaneously hypertensive rats. β1AR-selective antagonists (CGP20712A, atenolol, metoprolol reduced norepinephrine overflow to plasma equally efficient as β2AR-selective (ICI-118551 and β1+2AR (nadolol antagonists in both strains. Neither antagonist lowered epinephrine secretion. Atenolol, which does not cross the blood-brain barrier, reduced norepinephrine overflow after adrenalectomy, adrenalectomy+ganglion blockade, losartan or nephrectomy. Atenolol and metoprolol reduced resting cardiac work load. During tyramine-stimulated norepinephrine release, they had little effect on work load, and increased the transient rise in total peripheral vascular resistance, particularly atenolol when combined with losartan. In conclusion, β1AR, like β2AR, stimulated norepinephrine but not epinephrine release, independent of adrenal catecholamines, ganglion transmission, or renal renin release/angiotensin AT1-receptor activation. β1AR therefore functioned as a peripheral, presynaptic, facilitating auto-receptor. Like tyramine, hypoxia may induce NET-mediated release. Augmented tyramine-induced vasoconstriction, as observed after injection of β1AR-blocker, particularly atenolol combined with losartan, may hamper organ perfusion, and may have clinical relevance in hypoxic conditions such as

  17. The effect of TNF-alpha blockers on psychometric measures in ankylosing spondylitis patients: a preliminary observation.

    Science.gov (United States)

    Arısoy, Ozden; Bes, Cemal; Cifci, Cigdem; Sercan, Mustafa; Soy, Mehmet

    2013-07-01

    There is a high co-morbidity between chronic inflammatory disorders and depression. Proinflammatory cytokines like TNF-α seem to play a central role in the pathogenesis of these disorders, and its neutralization provides a potent treatment for inflammatory disorders. Few studies showed that TNF-α blockers also caused an improvement in depressive symptoms associated with these chronic inflammatory disorders. To evaluate the effectiveness of TNF-α blockers on symptoms of ankylosing spondylitis (AS), depression, anxiety and quality of life, 9 AS patients resistant to classical therapy were enrolled and followed-up at 2nd and 6th weeks after a TNF-α blocker was started. Hamilton Depression and Anxiety Scales (HAM-D, HAM-A), Hospital Depression and Anxiety Questionnaire (HAD), Quality of Life Scale (SF36) and AS severity index (BASDAI) were applied to the patients at weeks 0, 2 and 6. ESR and CRP were evaluated to monitor biological disease activity. There was a significant reduction in HAM-D (p = 0.00), HAM-A (p = 0.00), HAD anxiety scores (p = 0.02) and a significant improvement in SF36 physical function (p = 0.00), physical role limitations (p = 0.00), bodily pain (p = 0.05), general health (p = 0.01), vitality (p = 0.03) and emotional role limitations (p = 0.00) subscales, BASDAI scores (p = 0.00), ESR (p = 0.00) and CRP (p = 0.00). Change in clinical disease activity (BASDAI) was not correlated with change in depression-anxiety scores, while change in biological disease activity (CRP) was correlated with change in depression-anxiety scores. TNFα blockers may have a potential antidepressant effect besides its anti-inflammatory effect that seems to be independent of its clinical effect.

  18. Comparison of the Tocolytic Effects of Ritodrine and Ca++ Channel Blockers on Serum Oestradiol and Progesterone Levels

    OpenAIRE

    2003-01-01

    Experimental pregnancy was induced with gonadal steroids in in vivo ovariectomized rats. Conditions for premature delivery were established by giving a salt-rich diet and administering oxytocin to induce high-risk pregnancy. In order to avoid early delivery, a betamimetic ritodrine and the Ca++ channel blockers nitrendipine and nicardipine were administered to three separate groups. The effects of these three tocolytic agents were examined by determining serum oestradiol and progesterone ...

  19. Angiotensin II receptor blockers and cardiovascular protection: Focus on left ventricular hypertrophy regression and atrial fibrillation prevention

    Directory of Open Access Journals (Sweden)

    Cesare Cuspidi

    2008-02-01

    Full Text Available Cesare Cuspidi1,2, Francesca Negri2, Alberto Zanchetti31Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy; 2Policlinico di Monza; 3Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università di Milano, and Istituto Auxologico Italiano, Milan, ItalyAbstract: Left ventricular hypertrophy (LVH and atrial fibrillation (AF are strong predictors of cardiovascular (CV morbidity and mortality, independently of blood pressure levels and other modifiable and nonmodifiable risk factors. The actions of circulating and tissue angiotensin II, mediated by AT1 receptors, play an important role in the development of a wide spectrum of cardiovascular alterations, including LVH, atrial enlargement and AF. Growing experimental and clinical evidence suggests that antihypertensive drugs may exert different effects on LVH regression and new onset AF in the setting of arterial hypertension. Since a number of large and adequately designed studies have found angiotensin II receptor blockers (ARBs to be more effective in reducing LVH than beta-blockers and data are also available showing their effectiveness in preventing new or