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Sample records for blocker qx-314 produces

  1. Acid solution is a suitable medium for introducing QX-314 into nociceptors through TRPV1 channels to produce sensory-specific analgesic effects.

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    He Liu

    Full Text Available BACKGROUND: Previous studies have demonstrated that QX-314, an intracellular sodium channel blocker, can enter into nociceptors through capsaicin-activated TRPV1 or permeation of the membrane by chemical enhancers to produce a sensory-selective blockade. However, the obvious side effects of these combinations limit the application of QX-314. A new strategy for targeting delivery of QX-314 into nociceptors needs further investigation. The aim of this study is to test whether acidic QX-314, when dissolves in acidic solution directly, can enter into nociceptors through acid-activated TRPV1 and block sodium channels from the intracellular side to produce a sensory-specific analgesic effect. METHODOLOGY/PRINCIPAL FINDINGS: Acidic solution or noradrenaline was injected intraplantarly to induce acute pain behavior in mice. A chronic constrictive injury model was performed to induce chronic neuropathic pain. A sciatic nerve blockade model was used to evaluate the sensory-specific analgesic effects of acidic QX-314. Thermal and mechanical hyperalgesia were measured by using radiant heat and electronic von Frey filaments test. Spinal Fos protein expression was determined by immunohistochemistry. The expression of p-ERK was detected by western blot assay. Whole cell clamp recording was performed to measure action potentials and total sodium current in rats DRG neurons. We found that pH 5.0 PBS solution induced behavioral hyperalgesia accompanied with the increased expression of spinal Fos protein and p-ERK. Pretreatment with pH 5.0 QX-314, and not pH 7.4 QX-314, alleviated pain behavior, inhibited the increased spinal Fos protein and p-ERK expression induced by pH 5.0 PBS or norepinephrine, blocked sodium currents and abolished the production of action potentials evoked by current injection. The above effects were prevented by TRPV1 channel inhibitor SB366791, but not by ASIC channel inhibitor amiloride. Furthermore, acidic QX-314 employed adjacent to the

  2. Bupivacaine-induced cellular entry of QX-314 and its contribution to differential nerve block

    Science.gov (United States)

    Brenneis, C; Kistner, K; Puopolo, M; Jo, S; Roberson, DP; Sisignano, M; Segal, D; Cobos, EJ; Wainger, BJ; Labocha, S; Ferreirós, N; Hehn, C; Tran, J; Geisslinger, G; Reeh, PW; Bean, BP; Woolf, C J

    2014-01-01

    Background and Purpose: Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N-ethyl bromide (QX-314) through transient receptor potential V1 (TRPV1) channels into nociceptors. We screened local anaesthetics for their capacity to activate TRP channels, and characterized the nerve block obtained by combination with QX-314. Experimental Approach: We investigated TRP channel activation in dorsal root ganglion (DRG) neurons by calcium imaging and patch-clamp recordings, and cellular QX-314 uptake by MS. To characterize nerve block, compound action potential (CAP) recordings from isolated nerves and behavioural responses were analysed. Key Results: Of the 12 compounds tested, bupivacaine was the most potent activator of ruthenium red-sensitive calcium entry in DRG neurons and activated heterologously expressed TRPA1 channels. QX-314 permeated through TRPA1 channels and accumulated intracellularly after activation of these channels. Upon sciatic injections, QX-314 markedly prolonged bupivacaine's nociceptive block and also extended (to a lesser degree) its motor block. Bupivacaine's blockade of C-, but not A-fibre, CAPs in sciatic nerves was extended by co-application of QX-314. Surprisingly, however, this action was the same in wild-type, TRPA1-knockout and TRPV1/TRPA1-double knockout mice, suggesting a TRP-channel independent entry pathway. Consistent with this, high doses of bupivacaine promoted a non-selective, cellular uptake of QX-314. Conclusions and Implications: Bupivacaine, combined with QX-314, produced a long-lasting sensory nerve block. This did not require QX-314 permeation through TRPA1, although bupivacaine activated these channels. Regardless of entry pathway, the greatly extended duration of block produced by QX-314 and bupivacaine may be clinically useful. PMID:24117225

  3. The quaternary lidocaine derivative, QX-314, exerts biphasic effects on transient receptor potential vanilloid subtype 1 channels in vitro

    DEFF Research Database (Denmark)

    Rivera-Acevedo, Ricardo E; Pless, Stephan Alexander; Ahern, Christopher A

    2011-01-01

    BACKGROUND: Transient receptor potential vanilloid subfamily member 1 (TRPV1) channels are important integrators of noxious stimuli with pronounced expression in nociceptive neurons. The experimental local anesthetic, QX-314, a quaternary (i.e., permanently charged) lidocaine derivative, recently...... concentrations (less than 1 mM), QX-314 potently inhibited capsaicin-evoked TRPV1 currents with an IC₅₀ of 8.0 ± 0.6 μM. CONCLUSIONS: The results of this study show that the quaternary lidocaine derivative QX-314 exerts biphasic effects on TRPV1 channels, inhibiting capsaicin-evoked TRPV1 currents at lower...

  4. Beta Blockers

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

  5. H2 blockers

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

  6. Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels☆

    Science.gov (United States)

    Cuypers, Eva; Abdel-Mottaleb, Yousra; Kopljar, Ivan; Rainier, Jon D.; Raes, Adam L.; Snyders, Dirk J.; Tytgat, Jan

    2008-01-01

    In this study, we pharmacologically characterized gambierol, a marine polycyclic ether toxin which is produced by the dinoflagellate Gambierdiscus toxicus. Besides several other polycyclic ether toxins like ciguatoxins, this scarcely studied toxin is one of the compounds that may be responsible for ciguatera fish poisoning (CFP). Unfortunately, the biological target(s) that underlies CFP is still partly unknown. Today, ciguatoxins are described to specifically activate voltage-gated sodium channels by interacting with their receptor site 5. But some dispute about the role of gambierol in the CFP story shows up: some describe voltage-gated sodium channels as the target, while others pinpoint voltage-gated potassium channels as targets. Since gambierol was never tested on isolated ion channels before, it was subjected in this work to extensive screening on a panel of 17 ion channels: nine cloned voltage-gated ion channels (mammalian Nav1.1–Nav1.8 and insect Para) and eight cloned voltage-gated potassium channels (mammalian Kv1.1–Kv1.6, hERG and insect ShakerIR) expressed in Xenopus laevis oocytes using two-electrode voltage-clamp technique. All tested sodium channel subtypes are insensitive to gambierol concentrations up to 10 μM. In contrast, Kv1.2 is the most sensitive voltage-gated potassium channel subtype with almost full block (>97%) and an half maximal inhibitory concentration (IC50) of 34.5 nM. To the best of our knowledge, this is the first study where the selectivity of gambierol is tested on isolated voltage-gated ion channels. Therefore, these results lead to a better understanding of gambierol and its possible role in CFP and they may also be useful in the development of more effective treatments. PMID:18313714

  7. Calcium Channel Blockers

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

  8. Beta-blockers

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    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....

  9. Calcium channel blocker poisoning

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    Miran Brvar

    2005-04-01

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

  10. Calcium channel blocker overdose

    Science.gov (United States)

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

  11. The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices.

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    Smith, Maree T; Cabot, Peter J; Ross, Fraser B; Robertson, Alan D; Lewis, Richard J

    2002-03-01

    N-type calcium channels modulate the release of key pro-nociceptive neurotransmitters such as glutamate and substance P (SP) in the central nervous system. Considerable research interest has focused on the therapeutic potential of the peptidic omega-conopeptides, GVIA and MVIIA as novel analgesic agents, due to their potent inhibition of N-type calcium channels. Recently, the novel peptidic N-type calcium channel blocker, AM336, was isolated from the venom of the cone snail, Conus catus. Thus, the aims of this study were to (i) document the antinociceptive effects of AM336 (also known as CVID) relative to MVIIA following intrathecal (i.t.) bolus dosing in rats with adjuvant-induced chronic inflammatory pain of the right hindpaw and to (ii) quantify the inhibitory effects of AM336 relative to MVIIA on K+-evoked SP release from slices of rat spinal cord. Both AM336 and MVIIA inhibited the K+-evoked release of the pro-nociceptive neurotransmitter, SP, from rat spinal cord slices in a concentration-dependent manner (EC50 values=21.1 and 62.9 nM, respectively), consistent with the antinociceptive actions of omega-conopeptides. Following acute i.t. dosing, AM336 evoked dose-dependent antinociception (ED50 approximately 0.110 nmol) but the doses required to produce side-effects were an order of magnitude larger than the doses required to produce antinociception. For i.t. doses of MVIIA0.07 nmol, produced a dose-dependent decrease in antinociception but the incidence and severity of the side-effects continued to increase for all doses of MVIIA investigated, suggesting that dose-titration with MVIIA in the clinical setting, may be difficult.

  12. Can Beta Blockers Cause Weight Gain?

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

  13. How Do Beta Blocker Drugs Affect Exercise?

    Science.gov (United States)

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

  14. Calcium channel blockers and prostate cancer.

    Science.gov (United States)

    Loughlin, Kevin R

    2014-07-01

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

  15. Renoprotective effect of calcium channel blockers

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    Dimković Nada

    2009-01-01

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

  16. Misperceptions About β-Blockers and Diuretics

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

    2003-01-01

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

  17. β1-Adrenoceptor blocker aggravated ventricular arrhythmia.

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

    2013-11-01

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

  18. Nano-engineered microcapsules boost the treatment of persistent pain

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    Kopach, Olga; Zheng, Kayiu; Dong, Luo; Sapelkin, Andrei; Voitenko, Nana; Sukhorukov, Gleb B.; Rusakov, Dmitri A.

    2018-01-01

    Abstract Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10–20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments. PMID:29383961

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Discovery and Development of Calcium Channel Blockers

    OpenAIRE

    Godfraind, Théophile

    2017-01-01

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

  1. 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.

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

    Science.gov (United States)

    2017-10-01

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

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

    Science.gov (United States)

    Garg, Rakesh; Pandit, Anuja

    2017-06-01

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

  4. Detecting Anti Ad-blockers in the Wild

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    Mughees Muhammad Haris

    2017-07-01

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

  5. 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.

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

    Science.gov (United States)

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

    2016-02-25

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

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

    African Journals Online (AJOL)

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

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  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. © The Author(s) 2014.

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

    Directory of Open Access Journals (Sweden)

    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

  11. Discovery and Development of Calcium Channel Blockers

    Science.gov (United States)

    Godfraind, Théophile

    2017-01-01

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

  12. Discovery and Development of Calcium Channel Blockers.

    Science.gov (United States)

    Godfraind, Théophile

    2017-01-01

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

  13. Discovery and Development of Calcium Channel Blockers

    Directory of Open Access Journals (Sweden)

    Théophile Godfraind

    2017-05-01

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

  14. 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.

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

    Science.gov (United States)

    2016-10-01

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

  16. 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....

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

    Science.gov (United States)

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

    2011-12-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Science.gov (United States)

    Ram, C Ventika S

    2004-10-01

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Ni Putu Wirantari

    2013-07-01

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

  2. Beta-blockers in cirrhosis and refractory ascites

    DEFF Research Database (Denmark)

    Kimer, Nina; Feineis, Martin; Møller, Søren

    2015-01-01

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

  3. Cocaine-induced closures of single batrachotoxin-activated Na+ channels in planar lipid bilayers

    Science.gov (United States)

    1988-01-01

    Batrachotoxin (BTX)-activated Na+ channels from rabbit skeletal muscle were incorporated into planar lipid bilayers. These channels appear to open most of the time at voltages greater than -60 mV. Local anesthetics, including QX-314, bupivacaine, and cocaine when applied internally, induce different durations of channel closures and can be characterized as "fast" (mean closed duration less than 10 ms at +50 mV), "intermediate" (approximately 80 ms), and "slow" (approximately 400 ms) blockers, respectively. The action of these local anesthetics on the Na+ channel is voltage dependent; larger depolarizations give rise to stronger binding interactions. Both the dose-response curve and the kinetics of the cocaine-induced closures indicate that there is a single class of cocaine-binding site. QX-314, though a quaternary-amine local anesthetic, apparently competes with the same binding site. External cocaine or bupivacaine application is almost as effective as internal application, whereas external QX-314 is ineffective. Interestingly, external Na+ ions reduce the cocaine binding affinity drastically, whereas internal Na+ ions have little effect. Both the cocaine association and dissociation rate constants are altered when external Na+ ion concentrations are raised. We conclude that (a) one cocaine molecule closes one BTX-activated Na+ channel in an all-or-none manner, (b) the binding affinity of cocaine is voltage sensitive, (c) this cocaine binding site can be reached by a hydrophilic pathway through internal surface and by a hydrophobic pathway through bilayer membrane, and (d) that this binding site interacts indirectly with the Na+ ions. A direct interaction between the receptor and Na+ ions seems minimal. PMID:2851029

  4. The Impact of UPFC on Power Swing Blocker

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    African Journals Online (AJOL)

    Adele

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

  6. Norepinephrine transporter blocker atomoxetine increases salivary alpha amylase

    NARCIS (Netherlands)

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

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  10. 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...

  11. Evaluation of nitrendipine channel blocker a new calcium

    African Journals Online (AJOL)

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

  12. Calcium-channel blockers in pulmonary arterial hypertension.

    Science.gov (United States)

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

    2013-01-01

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

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

    CERN Multimedia

    CERN. Geneva

    2015-01-01

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

  14. 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 }.

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

    NARCIS (Netherlands)

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

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

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

    Directory of Open Access Journals (Sweden)

    A. A. Aleksandrov

    2008-01-01

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

  17. Use of β-Blockers in Pulmonary Hypertension.

    Science.gov (United States)

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

    2017-04-01

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yona Goldshmit

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    C. Müller

    2010-01-01

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

  2. 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.

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

    Science.gov (United States)

    Mohokum, Melvin; Hartmann, Peter; Schlattmann, Peter

    2012-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Sanjai Sinha

    2009-12-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    David C Evans

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  8. 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.

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

    Science.gov (United States)

    Mitsuda, M; Nomoto, M; Iwata, S

    1999-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Serkan Doğan

    2012-01-01

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

  11. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  14. Effects of Na+ channel blockers on the restitution of refractory period, conduction time, and excitation wavelength in perfused guinea-pig heart.

    Directory of Open Access Journals (Sweden)

    Oleg E Osadchii

    Full Text Available Na+ channel blockers flecainide and quinidine can increase propensity to ventricular tachyarrhythmia, whereas lidocaine and mexiletine are recognized as safe antiarrhythmics. Clinically, ventricular fibrillation is often precipitated by transient tachycardia that reduces action potential duration, suggesting that a critical shortening of the excitation wavelength (EW may contribute to the arrhythmic substrate. This study examined whether different INa blockers can produce contrasting effects on the rate adaptation of the EW, which would explain the difference in their safety profile. In perfused guinea-pig hearts, effective refractory periods (ERP, conduction times, and EW values were determined over a wide range of cardiac pacing intervals. All INa blockers tested were found to flatten the slope of ERP restitution, indicating antiarrhythmic tendency. However, with flecainide and quinidine, the beneficial changes in ERP were reversed owing to the use-dependent conduction slowing, thereby leading to significantly steepened restitution of the EW. In contrast, lidocaine and mexiletine had no effect on ventricular conduction, and therefore reduced the slope of the EW restitution, as expected from their effect on ERP. These findings suggest that the slope of the EW restitution is an important electrophysiological determinant which can discriminate INa blockers with proarrhythmic and antiarrhythmic profile.

  15. Effects of Na+ channel blockers on the restitution of refractory period, conduction time, and excitation wavelength in perfused guinea-pig heart.

    Science.gov (United States)

    Osadchii, Oleg E

    2017-01-01

    Na+ channel blockers flecainide and quinidine can increase propensity to ventricular tachyarrhythmia, whereas lidocaine and mexiletine are recognized as safe antiarrhythmics. Clinically, ventricular fibrillation is often precipitated by transient tachycardia that reduces action potential duration, suggesting that a critical shortening of the excitation wavelength (EW) may contribute to the arrhythmic substrate. This study examined whether different INa blockers can produce contrasting effects on the rate adaptation of the EW, which would explain the difference in their safety profile. In perfused guinea-pig hearts, effective refractory periods (ERP), conduction times, and EW values were determined over a wide range of cardiac pacing intervals. All INa blockers tested were found to flatten the slope of ERP restitution, indicating antiarrhythmic tendency. However, with flecainide and quinidine, the beneficial changes in ERP were reversed owing to the use-dependent conduction slowing, thereby leading to significantly steepened restitution of the EW. In contrast, lidocaine and mexiletine had no effect on ventricular conduction, and therefore reduced the slope of the EW restitution, as expected from their effect on ERP. These findings suggest that the slope of the EW restitution is an important electrophysiological determinant which can discriminate INa blockers with proarrhythmic and antiarrhythmic profile.

  16. Pharmacoepidemiological Beta-blockers consumer research in Ukraine

    Directory of Open Access Journals (Sweden)

    O. Ya. Mishchenko

    2012-12-01

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

  17. 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.

  18. Effect of alpha1-blockers on stentless ureteroscopic lithotripsy

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    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.

  19. 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 ...

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

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Morgan, Marsha Y.

    2017-01-01

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

  1. 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...

  2. 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....

  3. 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.

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

    Science.gov (United States)

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

    2003-06-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  6. 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

  7. Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  8. 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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  11. A comparison of the disconnection technique with continuous bronchial suction for lung deflation when using the Arndt endobronchial blocker during video-assisted thoracoscopy: A randomised trial.

    Science.gov (United States)

    El-Tahan, Mohamed R

    2015-06-01

    The use of the Arndt endobronchial blocker has not gained widespread acceptance during video-assisted thoracoscopic surgery (VATS) because of its high cost and longer time to operative lung collapse especially in patients with chronic obstructive pulmonary disease (COPD). The use of a ventilator disconnection technique has been shown to produce a comparable degree of lung collapse when used with either a double-lumen tube or an Arndt endobronchial blocker. We hypothesised that the use of bronchial suction through the suction port of the endobronchial blocker would be associated with a comparable time to achieve optimum lung collapse as the disconnection technique. A randomised, double-blind study. Single university hospital. Fifty-eight patients with spontaneous pneumothorax scheduled for elective VATS using the Arndt endobronchial blocker for one-lung ventilation (OLV). Patients were randomly assigned to one of two groups (n = 29 per group) to deflate the operative lung with either disconnection of the endotracheal tube from the ventilator for 60 s prior to inflation of the endobronchial blocker or connection of a suction pressure of -30 cmH2O to the suction port of the endobronchial blocker through the barrel of a 1 ml syringe. The primary outcome was the time to total lung collapse. Secondary outcomes included surgeon rating of lung collapse, overall surgeon satisfaction, need for further fibreoptic bronchial suction manoeuvres and intraoperative hypoxaemia. The bronchial suction technique was associated with a significantly shorter time to total lung collapse than the disconnection method [93 (95% confidence interval, 95% CI 81.3 to 103.7) vs. 197 (95% CI 157.4 to 237) s respectively; P < 0.001]. Both the disconnection and bronchial suction groups had a comparable surgical rating of excellent lung collapse 40 min after the start of OLV (65.5 vs. 79.3%, respectively; P = 0.24), overall surgeon satisfaction [median (interquartile range, IQR) 9 (8 to 10) vs. 9 (8

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

    Directory of Open Access Journals (Sweden)

    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.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-11-07

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  16. Pulmonary vasoconstrictor action of KCNQ potassium channel blockers

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    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

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

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    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

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

    Science.gov (United States)

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

    2017-08-01

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

  19. 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.

  20. 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...

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

    Directory of Open Access Journals (Sweden)

    Fitzgerald PJ

    2012-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Georg Nickenig

    2006-03-01

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

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

    Science.gov (United States)

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

    2017-12-13

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Chia, N; Fulcher, J; Keech, A

    2016-06-01

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

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

    Science.gov (United States)

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

    2014-03-01

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

  7. NERVE EXCITABILITY CHANGES AFTER NA(V)1.8 CHANNEL BLOCKER TREATMENT IN MICE DEFICIENT OF MYELIN PROTEIN P-0

    DEFF Research Database (Denmark)

    Moldovan, M.; Rosberg, M. R.; Alvarez Herrero, Susana

    2016-01-01

    Mice deficient of myelin protein zero (P0) are established models of demyelinating Charcot-Marie-Tooth (CMT) disease. Recent work form our laboratory indicated that in severely affected P0−/− as well as in P0+/− (modeling CMT1B), the neuropathy is aggravated by associated changes in voltage...... function up to 2 hours after the blockers. Overall, the baseline excitability measures were much more abnormal in P0−/− at 4 months as compared to P0+/− at 20 months. Nevertheless, in both models, the NaV1.8 blockers produced similar deviations in excitability at a dose of 100 mg/Kg. Most notably...

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

    Directory of Open Access Journals (Sweden)

    Juliana F. Silva

    2017-10-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Science.gov (United States)

    Iwata, S; Nomoto, M; Fukuda, T

    1993-03-01

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

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

    NARCIS (Netherlands)

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

    1994-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  13. 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.

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  17. 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.

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

    OpenAIRE

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

    2017-01-01

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

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

    Science.gov (United States)

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

    1998-01-01

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

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

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

    Science.gov (United States)

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

    2018-03-01

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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Robert Weiss

    2006-09-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

  4. Recombinant expression of margatoxin and agitoxin-2 in Pichia pastoris: an efficient method for production of KV1.3 channel blockers.

    Directory of Open Access Journals (Sweden)

    Raveendra Anangi

    Full Text Available The K(v1.3 voltage-gated potassium channel regulates membrane potential and calcium signaling in human effector memory T cells that are key mediators of autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. Thus, subtype-specific K(v1.3 blockers have potential for treatment of autoimmune diseases. Several K(v1.3 channel blockers have been characterized from scorpion venom, all of which have an α/β scaffold stabilized by 3-4 intramolecular disulfide bridges. Chemical synthesis is commonly used for producing these disulfide-rich peptides but this approach is time consuming and not cost effective for production of mutants, fusion proteins, fluorescently tagged toxins, or isotopically labelled peptides for NMR studies. Recombinant production of K(v1.3 blockers in the cytoplasm of E. coli generally necessitates oxidative refolding of the peptides in order to form their native disulfide architecture. An alternative approach that avoids the need for refolding is expression of peptides in the periplasm of E. coli but this often produces low yields. Thus, we developed an efficient Pichia pastoris expression system for production of K(v1.3 blockers using margatoxin (MgTx and agitoxin-2 (AgTx2 as prototypic examples. The Pichia system enabled these toxins to be obtained in high yield (12-18 mg/L. NMR experiments revealed that the recombinant toxins adopt their native fold without the need for refolding, and electrophysiological recordings demonstrated that they are almost equipotent with the native toxins in blocking K(V1.3 (IC(50 values of 201±39 pM and 97 ± 3 pM for recombinant AgTx2 and MgTx, respectively. Furthermore, both recombinant toxins inhibited T-lymphocyte proliferation. A MgTx mutant in which the key pharmacophore residue K28 was mutated to alanine was ineffective at blocking K(V1.3 and it failed to inhibit T-lymphocyte proliferation. Thus, the approach described here provides an efficient method of

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

    NARCIS (Netherlands)

    Brewster, Lizzy M.; Seedat, Yackoob K.

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  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. Differential effects of 3 beta blockers on lipid peroxidation in hyperthyroid muscle.

    Science.gov (United States)

    Asayama, K; Hayashibe, H; Dobashi, K; Kato, K

    1990-08-01

    To determine whether beta blockade protects against the acceleration of lipid peroxidation in hyperthyroid rat soleus (slow-oxidative) muscle, in vivo chronic (3 weeks) effects of 3 beta blockers with different ancillary properties on mitochondrial oxidative enzymes, antioxidant enzymes, and thiobarbituric acid-reactive substances were investigated. The rats were rendered hyperthyroid by the administration of thyroxine and treated simultaneously with either carteolol (a nonselective blocker with partial agonist activity; 30 mg/kg/day), atenolol (a beta 1-selective blocker; 50 mg/kg/day), or arotinolol (a nonselective blocker with weak alpha-blocking action; 50 mg/kg/day) over a 3 week period. Hyperthyroidism induced tachycardia, an increase in the mitochondrial oxidative enzymes, manganese (mitochondrial) superoxide dismutase and thiobarbituric acid-reactive substances, and a decrease in the other antioxidant enzymes. The tachycardia was alleviated completely by either atenolol or arotinolol, but partially by carteolol. Arotinolol, but neither carteolol nor atenolol, inhibited the increase in oxidative enzymes and thiobarbituric acid-reactive substances. The levels of antioxidant enzymes were minimally affected by the beta-blocker treatment. Beta 2-, and possibly alpha- as well, but not beta 1-, blockade suppressed mitochondrial hypermetabolism and protected against peroxidative injury in the hyperthyroid soleus muscle. Partial agonist activity was not beneficial.

  9. Use of Calcium Channel Blockers and Risk of Breast Cancer: A Population-based Cohort Study.

    Science.gov (United States)

    Azoulay, Laurent; Soldera, Sara; Yin, Hui; Bouganim, Nathaniel

    2016-07-01

    Several observational studies have associated use of calcium channel blockers with an increased risk of breast cancer, but this association remains controversial. The objective of this study was to determine whether these drugs are associated with an increased risk of breast cancer overall, and to assess whether this risk varies with cumulative duration of use. We identified a cohort of 273,152 women newly treated with antihypertensive drugs between 1 January 1995 and 31 December 2009, followed until 31 December 2010, using the UK Clinical Practice Research Datalink. We treated calcium channel blocker use as a time-varying variable, and lagged exposure by 1 year for latency considerations and to minimize reverse causality. We used time-dependent Cox proportional hazards models to estimate adjusted hazard ratios with 95% confidence intervals of incident breast cancer associated with use of calcium channel blockers overall and by cumulative duration of use (cancer (incidence rate: 2.9 per 1,000 per year). Compared with use of other antihypertensive drugs, use of calcium channel blockers was not associated with increased risk of breast cancer overall (hazard ratio: 0.97, 95% confidence interval: 0.91, 1.03). Similarly, there was no evidence of a duration-response relationship in terms of cumulative duration of use (P trend = 0.26). The results of this large population-based study indicate that long-term use of calcium channel blockers is not associated with an increased risk of breast cancer.

  10. Receptor blockers - general aspects with respect to their use in domestic animal reproduction.

    Science.gov (United States)

    Hoffmann, B; Schuler, G

    2000-07-02

    Receptor blockers compete with the respective agonist for binding to a given receptor without inducing complete signal transduction. In recent years, major interest has focused on sex-steroid hormone receptor blockers (antagonists). Indications have been obtained that inadequate changes in receptor conformation and subsequent failure of transcriptional activation are major events preventing hormonal activity. However, various subtypes and variants of receptors and receptor mutations have also been identified. Expression of antihormonal effects may vary depending on the type of receptor the blocker is bound to. Hence, receptor blockers may also have an inherent agonistic activity. Aglepristone is the first antiprogestin registered for veterinary use with the indication "interruption or prevention of pregnancy"; similarly, these types of compounds were successfully used for induction of parturition in the dog and cat and for conservative treatment of pyometra in the dog. Moreover, application of antiprogestins has clearly demonstrated the role of progesterone as a major factor controlling overt pseudopregnancy in dogs. With respect to farm animals, parturition was induced in cows without an increased incidence of retained fetal membranes. Other than antiprogestins, antioestrogens and antiandrogens are still in a more experimental phase. In particular for use in humans, high-affinity blockers binding to the oxytocin/vasopressin receptor are in development; they exert distinct tocolytic activities. Also, the release of GnRH can be inhibited by respective antagonists; however, their use in reproduction is still hampered by the high dose requirement and the side effects observed.

  11. [Can preoperative administration of H2 blocker reduce the incidence of postoperative nausea and vomiting (PONV)?].

    Science.gov (United States)

    Nozaki, Chisato; Morioka, Nobutada; Kinoshita, Maho; Takada, Mikiko; Ozaki, Makoto

    2007-10-01

    PONV is a complication that reduces a patient's quality of life (QOL). Recently, it was reported that PONV is reduced by preoperative administration of histamine receptor (H1 and H2) inhibitor. In the present study, based on the hypothesis that PONV might be reduced by preoperative administration of H2 blocker, we examined the effect of preoperative administration of H2 blocker only on the incidence of PONV. Eighty seven patients having regular operations were randomly assigned into two groups; the control (C), and the H2 blocker (F) groups. In the operating room, 20 min after intravenous injection of famotidine 20 mg as H2 blocker, anesthesia was maintened by sevofluorane, oxygen, nitrous oxide, and fentanyl following the induction by fentanyl, propofol, and vecuronium. The frequency and extent of vomiting were observed and the patients were interviewed at postoperative hours 0-6 and 6-12. The incidences between the two groups were examined using the chi-squared test. No significant difference in the appearance of PONV was found between the F group and the C group. In women in the F group, the incidence of vomiting was lower. Preoperative administration of H2 blocker tends to reduce PONV in women.

  12. Outcomes in adolescents with postural orthostatic tachycardia syndrome treated with midodrine and beta-blockers.

    Science.gov (United States)

    Lai, Cindy C; Fischer, Philip R; Brands, Chad K; Fisher, Jennifer L; Porter, Co-Burn J; Driscoll, Sherilyn W; Graner, Kevin K

    2009-02-01

    Postural orthostatic tachycardia syndrome (POTS) is associated with debilitating fatigue, dizziness, and discomfort in previously healthy adolescents. The effects of medical therapy have not been well studied in this patient population. This study assessed the relative efficacy and impact of drug therapy on the functioning and quality of life in adolescents with POTS. A retrospective, single center, chart review analysis with a follow-up written survey was conducted on a group of 121 adolescents who had undergone autonomic reflex screening at the Mayo Clinic from 2002 to 2005 as part of an evaluation for possible POTS. Of 121 surveys sent, 47 adolescents returned a completed survey. In this cohort of patients, the two most commonly prescribed drug therapies were midodrine (n = 13) and beta-blockers (n = 14). Patients in the midodrine group were comparable to patients in the beta-blocker group in gender, age, pretreatment postural heart rate changes, and months from initial evaluation to survey completion. More patients treated with a beta-blocker reported improvement after visiting Mayo Clinic (100% vs 62%, P = 0.016) and more attributed their progress to medication (63.6% vs 36.4%, P = 0.011) than did those treated with midodrine. Treatment with both midodrine and beta-blockers was associated with overall improvement in POTS patients' general health; however, adolescents taking beta-blockers were more likely than those taking midodrine to credit the role of medications in their improvement.

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

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Sørensen, Flemming Steen

    2011-01-01

    on current methods to predict hERG blockers and the need of consistent data to improve the quality and performance of the in silico models. Finally, integration of network-based analysis on drugs inducing potentially long-QT syndrome and arrhythmia will be discussed as a new perspective for a better......The risk for cardiotoxic side effects represents a major problem in clinical studies of drug candidates and regulatory agencies have explicitly recommended that all new drug candidates should be tested for blockage of the human Ether-a-go-go Related-Gene (hERG) potassium channel. Indeed, several...... drugs with different therapeutic indications and recognized as hERG blockers were recently withdrawn due to the risk of QT prolongation, arrhythmia and Torsade de Pointes.In silico techniques can provide a priori knowledge of hERG blockers, thus reducing the costs associated with screening assays...

  14. 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.

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

    Science.gov (United States)

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

    2015-07-01

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

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

    Science.gov (United States)

    2013-01-01

    Background Clinicians are encouraged to take an individualized approach when treating hypertension in patients of African ancestry, but little is known about why the individual patient may respond well to calcium blockers and diuretics, but generally has an attenuated response to drugs inhibiting the renin-angiotensin system and to β-adrenergic blockers. Therefore, we systematically reviewed the factors associated with the differential drug response of patients of African ancestry to antihypertensive drug therapy. Methods Using the methodology of the systematic reviews narrative synthesis approach, we sought for published or unpublished studies that could explain the differential clinical efficacy of antihypertensive drugs in patients of African ancestry. PUBMED, EMBASE, LILACS, African Index Medicus and the Food and Drug Administration and European Medicines Agency databases were searched without language restriction from their inception through June 2012. Results We retrieved 3,763 papers, and included 72 reports that mainly considered the 4 major classes of antihypertensive drugs, calcium blockers, diuretics, drugs that interfere with the renin-angiotensin system and β-adrenergic blockers. Pharmacokinetics, plasma renin and genetic polymorphisms did not well predict the response of patients of African ancestry to antihypertensive drugs. An emerging view that low nitric oxide and high creatine kinase may explain individual responses to antihypertensive drugs unites previous observations, but currently clinical data are very limited. Conclusion Available data are inconclusive regarding why patients of African ancestry display the typical response to antihypertensive drugs. In lieu of biochemical or pharmacogenomic parameters, self-defined African ancestry seems the best available predictor of individual responses to antihypertensive drugs. PMID:23721258

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

    DEFF Research Database (Denmark)

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

    1991-01-01

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

  19. DOGMAS AND UPDATES ON THE USE OF BETA-BLOCKERS IN SECONDARY PREVENTION. FIRST PART.

    Directory of Open Access Journals (Sweden)

    Alberto Morales Salinas

    2011-08-01

    Full Text Available There is consensus on clinical guidelines that beta-blockers (BB provide unquestionable benefits in several environments of secondary prevention, such as heart failure and myocardial infarction. However, in everyday practice they are underused in contexts where they are not contraindicated. Such is the case of heart failure with ejection fraction. This article presents an analysis on the available evidence of beta blockers’ effectiveness in heart failure with ejection fraction. It is concluded that overwhelming evidence favours the use of beta-blockers in chronic heart failure with ejection fraction, whereas in episodes of acute decompensated heart failure, their suspension should be avoided whenever it is possible.

  20. Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

    DEFF Research Database (Denmark)

    Thiele, Maja; Wiest, Reiner; Gluud, Lise Lotte

    2013-01-01

    carcinoma via a reduction of the inflammatory load from the gut to the liver and inhibition of angiogenesis. Due to their effect on the portal pressure, non-selective beta-blockers are used for prevention of esophageal variceal bleeding. Recently, non-hemodynamic effects of beta-blockers have received......-up. Observational studies carry a high risk of bias. The meta-analytic approach may be used if the incidence and mortality of hepatocellular carcinoma can be extracted from trials on variceal bleeding and if the combined sample size and follow up is sufficient....

  1. The value of β-blockers administration during recovery phase of dobutamine stress echocardiography: a review.

    Science.gov (United States)

    Nguyen, James; Juneman, Elizabeth; Movahed, Mohammad Reza

    2013-07-01

    Dobutamine stress echocardiography (DSE) is a successful technique for detection of ischemia in patients with suspected coronary artery disease (CAD). There are some data that administration of β-blocker after peak infusion of dobutamine can improve sensitivity. The goal of this manuscript is to review the current literature in regard to the mechanism and accuracy of post-dobutamine β-blocker administration for ischemia detection. In this review, we present 2 case reports followed by detailed review of the literature. © 2013. This article is a U.S. Government work and is in the public domain in the USA.

  2. 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....

  3. Beta-blocker use and fall risk in older individuals: Original results from two studies with meta-analysis

    NARCIS (Netherlands)

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

    2017-01-01

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

  4. The pharmaco-economics of peri-operative beta-blocker and statin ...

    African Journals Online (AJOL)

    at 2 years.16.17 Because all drugs have potential adverse side- effects, we have attempted to determine the overall incidences of adverse cardiovascular outcomes potentially attributable to beta-blocker administration, including hypotension and bradycardia needing treatment, congestive heart failure, bronchospasm and ...

  5. β-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery

    DEFF Research Database (Denmark)

    Jørgensen, Mads E; Hlatky, Mark A; Køber, Lars Valeur

    2015-01-01

     (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). RESULTS: The baseline characteristics of the 14,644 patients who received β-blockers (65% female, mean [SD...

  6. 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.

  7. 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.

  8. 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...

  9. Discontinuation of alpha-blocker therapy in male lower urinary tract symptoms: A systematic review

    NARCIS (Netherlands)

    Hordijk, I.; Korteschiel, L.; Steffens, M.; Lisman-van Leeuwen, Y.; Blanker, M.

    2016-01-01

    Hypothesis / aims of study Alpha-blockers are the cornerstone for the medical treatment of male LUTS [1]. Despite the positive recommendation in all relevant guidelines, the efficacy of these drugs has been debated [2]. The Dutch general practitioners guideline Male LUTS recommends the

  10. 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

  11. Polymer membrane electrodes for sensitive potentiometric determination of beta-blockers.

    Science.gov (United States)

    Wassil, Anwar A; Farag, Abd El-Ftaah Bastawy; Moukdad, Fatma A

    2007-01-01

    The construction of PVC matrix-type beta-blockers (sotalol, carvedilol, and betaxolol) ion selective electrodes and their use for direct potentiometry of their respective species are described. The proposed sensors are based on the complex ion associates of beta-blockers with tungstophosphate (TP) and Ammonium Reineckate (Rein) ionophoris in poly vinyl chloride membrane (PVC) with Dioctylphthalate (DOP) plasticizer. The four electrodes (Beta-TP), (Sota-TP), (Carve-TP), and (Cave-Rein) show stable potential response with near Nernstian slope of 50.8, 33.7, 32.35, and 33 mv per decade, range of concentration 10-2-10-7 M beta-blockers. Selectivity coefficients data obtained for 11 different organic and inorganic ions are presented. The electrodes have fast response time (30 and 40 s) and were used over wide range of pH 4.5-8.5. Validation of the method according to the quality assurance standers shows suitability of proposed sensors for use in the quality control assessment of these drugs. The results obtained for the determination of beta-blockers with the proposed electrodes show average recoveries of 100.78% and a mean standard deviation of +/-1.2. The nominal are obtained. The data agree well with those obtained by standard methods.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  13. 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

  14. Radioprotective effect of calcium channel blockers against late rectal bleeding in prostate cancer.

    Science.gov (United States)

    Massaccesi, Mariangela; Ippolito, Edy; Deodato, Francesco; Cilla, Savino; Digesù, Cinzia; Macchia, Gabriella; Caravatta, Luciana; Picardi, Vincenzo; Mattiucci, Gian Carlo; Di Lallo, Alessandra; Cuscunà, Daniele; Cellini, Numa; Valentini, Vincenzo; Morganti, Alessio G

    2014-05-01

    This study was done to assess the impact of clinical factors and in particular the use of drugs for concomitant illnesses on late radiation-induced rectal bleeding in patients with prostate cancer. Patients with histologically proven prostate adenocarcinoma treated with radical radiotherapy and followed up for at least 6 months were selected. The correlation between late rectal bleeding and a number of factors was investigated by univariate and multivariate analysis. A total of 278 patients who underwent radiotherapy at our institution between October 2002 and May 2011 were selected. At univariate analysis, delivery of radiation doses higher than 70 Gy and use of angiotensin-converting enzyme inhibitors were associated with a higher incidence of rectal bleeding. Conversely, patients who used calcium channel blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5 %, p = 0.043). At multivariate analysis, use of calcium channel blockers was found to have a protective effect with a hazard ratio of 0.3 (95 % CI 0.12-0.96). Delivery of higher radiation doses was associated with an increased risk of rectal bleeding (hazard ratio 3.02, 95 % CI 1.23-7.38). Use of calcium channel blockers during and after radiotherapy treatment might have a protective effect against late rectal bleeding. If these results are reconfirmed by larger clinical series, calcium channel blockers may be tested as radioprotector agents in clinical trials.

  15. The pharmaco-economics of peri-operative beta-blocker and statin ...

    African Journals Online (AJOL)

    We conducted a pharmaco-economic analysis of the prospective peri-operative studies of beta-blocker and statin administration for major elective non-cardiac surgery, using the Discovery Health claims costs for 2004. This analysis shows that acute peri-operative beta-blockade and statin therapy could result in a cost ...

  16. Structural adaptation to ischemia in skeletal muscle: effects of blockers of the renin-angiotensin system

    NARCIS (Netherlands)

    Scheidegger, K. J.; Nelissen-Vrancken, M. H.; Leenders, P. J.; Daemen, M. J.; Smits, J. F.; Wood, J. M.

    1997-01-01

    To investigate the effects of long-term treatment with blockers of the renin-angiotensin system on capillarization and growth of fibers in ischemic hind-limb muscles and in muscles under normal growth conditions. Ischemia was induced by partial ligation of the left common iliac artery. Ischemia

  17. Allergy, histamine 1 receptor blockers, and the risk of multiple sclerosis.

    Science.gov (United States)

    Alonso, Alvaro; Jick, Susan S; Hernán, Miguel A

    2006-02-28

    It is unclear whether allergic diseases are associated with multiple sclerosis (MS), but histamine 1 receptor blockers, used in the treatment of allergic conditions, decreased the severity of experimental autoimmune encephalomyelitis (an animal model of MS). To assess the association of allergy history and use of histamine 1 receptor blockers with the risk of MS. Using a case-control study nested in the United Kingdom-based General Practice Research Database cohort, the authors identified 163 incident cases of MS with at least 3 years of follow-up before their first symptoms (index date). Up to 10 controls matched to the cases by age, sex, general practice, and time in the cohort were selected. Previous history of allergic disease and use of histamine 1 receptor blockers in the 3 years before the index date were assessed through computerized medical records. History of any allergic condition in the 3 years before the index date was not associated with MS risk (adjusted odds ratio [OR] 1.2, 95% CI 0.8 to 1.8). However, use of sedating histamine 1 receptor blockers was associated with decreased MS risk (adjusted OR 0.2, 95% CI 0.1 to 0.8). These results do not support a strong link between allergic conditions and multiple sclerosis (MS) risk but suggest a possible beneficial effect of antihistamines on the onset of MS.

  18. Interaction among hERG channel blockers is a potential mechanism of death in caffeine overdose.

    Science.gov (United States)

    Zheng, Jifeng; Zhao, Wei; Xu, Kai; Chen, Qingmao; Chen, Yingying; Shen, Yueliang; Xiao, Liping; Jiang, Liqin; Chen, Yuan

    2017-04-05

    Caffeine overdose death is due to cardiac arrest, but its mechanism has not been explored in detail. In this study, our data showed that caffeine significantly prolonged the heart rate-corrected QT interval (QTc) of rabbits in vivo (PCaffeine was also found to be a hERG channel blocker with an IC 50 of 5.04mM (n=5). Although these two findings likely link caffeine overdose death with hERG channel blockade, the amount of caffeine consumption needed to reach the IC 50 is very high. Further study demonstrated that addition another hERG blocker could lower the consumption of caffeine significantly, no matter whether two hERG blockers share the same binding sites. Our data does not rule out other possibility, however, it suggests that there is a potential causal relationship between caffeine overdose death with hERG channel and the interaction among these hERG blockers. Published by Elsevier B.V.

  19. Beta-Blockers and the Kidney: Implications for Renal Function and Renin Release.

    Science.gov (United States)

    Epstein, Murray; And Others

    1985-01-01

    Reviews and discusses current information on the human renal response as related to beta-blockers (antihypertension agents). Topic areas considered include cardioselectivity, renal hemodynamics, systemic hemodynamics, changes with acute and chronic administration, influence of dose, and others. Implications and an 11-item multiple-choice self-quiz…

  20. Muscle cramps and elevated serum creatine phosphokinase levels induced by beta-adrenoceptor blockers.

    Science.gov (United States)

    Imai, Y; Watanabe, N; Hashimoto, J; Nishiyama, A; Sakuma, H; Sekino, H; Omata, K; Abe, K

    1995-01-01

    We have assessed the propensity of beta-adrenoceptor blockers to cause muscle cramps and to raise the serum creatine phosphokinase (CPK) level in 78 patients with essential hypertension. After a control period, a beta-adrenoceptor blocker without intrinsic sympathomimetic activity (ISA; propranolol, metoprolol or arotinolol) was administered for three months. Thereafter, the patients were randomised to receive a beta-adrenoceptor blocker with ISA (pindolol or carteolol) for three months or a beta-adrenoceptor blocker without ISA for a further three months. This pattern was continued until all beta-adrenoceptor blockers had been given. At the end of each period, CPK and CPK-MB levels were measured. Of the 78 subjects, muscle cramps occurred in 27 during treatment with pindolol and 32 during treatment with carteolol. No complaints were made by subjects treated with propranolol and arotinolol, but muscle cramps were reported in 2 treated with metoprolol. While muscle cramps were caused both by pindolol and carteolol in 16 subjects, they were caused by either of these drugs in the remainder of the subjects. Muscle cramp occurred mainly in the calves when the patients were in bed at night. Serum CPK and CPK-MB levels increased significantly during treatment with pindolol (control period vs pindolol, CPK = 96 vs 133 IU.ml-1, CPK-MB = 14 vs 18 IU.ml-1) or carteolol (CPK = 117 IU.ml-1, CPK-MB = 18 IU.ml-1) while the levels during treatment with propranolol, arotinolol and metoprolol did not change from those in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. 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

  2. Beta-blocker use and fall risk in older individuals: Original results from two studies with meta-analysis.

    Science.gov (United States)

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

    2017-10-01

    To investigate the association between use of β-blockers and β-blocker characteristics - selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism - and fall risk. Data from two prospective studies were used, including community-dwelling individuals, n = 7662 (the Rotterdam Study) and 2407 (B-PROOF), all aged ≥55 years. Fall incidents were recorded prospectively. Time-varying β-blocker use was determined using pharmacy dispensing records. Cox proportional hazard models adjusted for age and sex were applied to determine the association between β-blocker use, their characteristics - selectivity, lipid solubility, ISA and CYP2D6 enzyme metabolism - and fall risk. The results of the studies were combined using meta-analyses. In total 2917 participants encountered a fall during a total follow-up time of 89 529 years. Meta-analysis indicated no association between use of any β-blocker, compared to nonuse, and fall risk, hazard ratio (HR) = 0.97 [95% confidence interval (CI) 0.88-1.06]. Use of a selective β-blocker was also not associated with fall risk, HR = 0.92 (95%CI 0.83-1.01). Use of a nonselective β-blocker was associated with an increased fall risk, HR = 1.22 (95%CI 1.01-1.48). Other β-blocker characteristics including lipid solubility and CYP2D6 enzyme metabolism were not associated with fall risk. Our study suggests that use of a nonselective β-blocker, contrary to selective β-blockers, is associated with an increased fall risk in an older population. In clinical practice, β-blockers have been shown effective for a variety of cardiovascular indications. However, fall risk should be considered when prescribing a β-blocker in this age group, and the pros and cons for β-blocker classes should be taken into consideration. © 2017 The British Pharmacological Society.

  3. Efficacy of Methylene Blue in an Experimental Model of Calcium Channel Blocker Induced Shock

    Science.gov (United States)

    Jang, David H.; Donovan, Sean; Nelson, Lewis S.; Bania, Theodore C.; Hoffman, Robert S.; Chu, Jason

    2014-01-01

    BACKGROUND Calcium channel blocker poisonings account for a substantial number of reported deaths from cardiovascular drugs. While supportive care is the mainstay of treatment, experimental therapies such as high dose insulin-euglycemia and lipid emulsion have been studied in animal models and used in humans. In the most severe cases even aggressive care is inadequate and deaths occur. In both experimental models and clinical cases of vasodilatory shock, methylene blue improves hemodynamic measures. Methylene blue acts as both a nitric oxide scavenger and inhibits guanylate cyclase that is responsible for the production of cGMP. Excessive cGMP production is associated with refractory vasodilatory shock in sepsis and anaphylaxis. The aim of this study was to determine the efficacy of methylene blue in an animal model of amlodipine-induced shock. METHODS Sprague-Dawley rats were anesthetized, ventilated and instrumented for continuous blood pressure and heart rate monitoring. The dose of amlodipine that produced death within 60 minutes was 17 mg/kg/hour (LD50). Rats were divided into 2 groups: amlodipine followed by methylene blue or amlodipine followed by normal saline (NS) with 15 rats in each group. Rats received methylene blue at 2 mg/kg over 5 mins or an equivalent amount of NS in three intervals from the start of the protocol: Minute 5, 30, and 60. The animals were observed for a total of 2 hours after the start of the protocol. Mortality risk and survival time were analyzed using Fisher’s exact test and Kaplan Meier survival analysis with the log rank test. RESULTS Overall, 1/15 (7%) rats in the saline-treated group survived to 120 minutes compared with 5/15 (33%) rats in the methylene blue-treated group (difference −26%, 95% CI –54%, 0.3%). The median survival time for the NS group was 42 min (95% CI, 28.1,55.9) and the methylene blue group was 109 min (95% CI, 93.9,124.1). Heart rate and MAP differences between groups were analyzed until 60 minutes

  4. Beta-blockers and health-related quality of life in patients with peripheral arterial disease and COPD.

    Science.gov (United States)

    van Gestel, Yvette R B M; Hoeks, Sanne E; Sin, Don D; Stam, Henk; Mertens, Frans W; Bax, Jeroen J; van Domburg, Ron T; Poldermans, Don

    2009-01-01

    Beta-blockers are frequently withheld in patients with cardiovascular disease who also have chronic obstructive pulmonary disease (COPD) because of concerns that they might provoke bronchospasm and cause deterioration in health status. Although beta1-selective beta-blockers are associated with reduced mortality in COPD patients, their effects on health status are unknown. The aim of this study was to investigate the relationship between beta-blockers and health-related quality of life (HRQOL) in patients with peripheral arterial disease and COPD. Of the original cohort of 3371 vascular surgery patients, 1310 had COPD of whom 469 survived during long-term follow-up. These COPD patients were sent the Short Form-36 (SF-36) health-related quality of life questionnaire, which was completed and returned by 326 (70%) patients. No significant differences in any of the SF-36 domains were observed between COPD patients who did and did not use beta-blockers (p > 0.05 for all). Furthermore, beta-blockers were not associated with any impairment in HRQOL among patients with COPD. Beta-blockers had no material impact on the HRQOL of patients with peripheral arterial disease who also had COPD. This suggests that beta-blockers can, in most circumstances, be administered to patients with COPD without impairment in HRQOL.

  5. Impact of beta-blocker treatment and nutritional status on glycemic response during exercise in patients with type 2 diabetes.

    Science.gov (United States)

    Ferland, Annie; Brassard, Patrice; Croteau, Sara; Lemieux, Simone; Bergeron, Jean; Lacroix, Stéphanie; Fournier, Lison; Poirier, Paul

    2007-01-01

    Most individuals with type 2 diabetes are affected by hypertension and thus have higher risk of cardiac complications. In addition to behavioural modifications, such as healthy food choices and regular physical activity, beta-blocker treatment may be considered to reduce morbidity and mortality, especially after a cardiovascular event. However, this medication is generally associated with a deleterious impact on glucose metabolism. The objective of the study was to assess the impact of beta-blocker treatment on glucose response during exercise in patients with type 2 diabetes, free of cardiovascular complications. Ten sedentary men, treated with diet and/or hypoglycemic agents have performed four exercise sessions at 60% of their V O2peak, in the fasted state or 2 hours following a standardized breakfast, with and without beta-blockers (atenolol 100 mg id for five consecutive days). Blood samples were drawn during the resting period, at 15-min intervals during the exercise session and during the recovery period. A reduction of blood glucose levels was observed following the exercise session in the postprandial state (48% and 44% reduction with and without beta-blockers respectively; P exercise performed in the fasted state had a minimal impact on glucose and insulin levels, whether with or without beta-blockers. beta-blocker treatment was not associated with increased baseline blood glucose or insulin levels in the fasted or the postprandial situation. Dietary status has a more important impact on plasma glucose and insulin modulation than short-term use of beta-blockers.

  6. Comparison the Efficacy of Four Different Alpha Blockers in the Treatment of Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Fatih Fırat

    2011-05-01

    Full Text Available Aim: Benign prostatic hyperplasia (BPH also known as nodular hyperplasia, benign enlargement of the prostate refers to the increase in size of the prostate in middle aged and elderly men. Although four different types of specific alpha blocker have been used in the treatment of BPH it remains controversial that which alpha adrenergic blocker is effective than others. The aim of this study is to compare the efficacy of 4 different alpha blockers agents on the treatment of BPH. Material and Methods: Between June 2005 and December 2008 a total of 135 consecutive patients with diagnosed of BPH were evaluated in our clinic. Patients were randomized into four groups according to alpha blocker types as fallows: group I, doxazosin 4 mg; group II, tamsulosin 0.4 mg; group III, terazosin 5 mg; and group IV, alfuzosin 10 mg. All patients were followed up with International Prostatic Symptom Score (IPSS, maximal urinary flow rates (Qmax and adverse effects were determined at baseline and again at least 3 months as efficacy parameters. Results: The mean age of the patients were 59.8±5.4 years, 58.9±6.4 years, 58.7±5.1 years, and 59.2±5.5 years in group I, group II, group III, and group IV, respectively (p>0.05. After 3 months treatment with alpha blockers the improvements in IPSS were found as 2.73, 3.73, 3.55 and 4.44 in group I, group II, group III, and group IV, respectively. Maximum urine flow rates increased as 2.81 ml/sec, 3.24 ml/sec, 3.88 ml/sec and 4.49 ml/sec in group I, group II, group III, and group IV, respectively. However, among 4 alpha blockers statistically significant difference was found only between doxazosin and alfuzosin groups according to uroflowmetry and IPSS results. According to these results, when compared adverse effect, the significant difference was observed only in tamsulosine group. Conclusions: As a result we can say that except retrograde ejaculation in tamsulosine group, adverse effects are not different between the

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

    Science.gov (United States)

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

    2017-01-01

    Effective medical expulsion for ureteric stones with α-blockers offers numerous advantages over surgical alternatives. However, its effectiveness remains uncertain and with the publication of new trial data, the available evidence requires reappraisal. The aim of this study was to assess the efficacy of α-blockers the management of ureteric lithiasis. A systematic review of the literature, with predefined search criteria, was conducted using PubMed and Embase. All randomised trials comparing α-blocker monotherapy to placebo or standard therapy were included. Stone expulsion rate was the primary outcome measure. Secondary outcome measures were time to stone expulsion, analgesic usage and pain scores. Subgroup analyses assessed individual adrenergic antagonists and variations in standard therapy. Sensitivity analysis was based on stone location, stone size, Cochrane Risk of Bias score and study protocol. Summary effects were calculated using a random-effect model and presented as Relative risks (RR) and mean differences (MD) for dichotomous and continuous outcome measures, respectively. Sixty-seven studies randomising 6654 patients were included in the meta-analysis. Stone expulsion rates improved with α-blockers (RR, 1.49; 95% CI 1.38-1.61). Contrast enhanced funnel showed evidence of publication bias. Stone expulsion time was 3.99 days (CI -4.75 to -3.23) shorter with α-blockers. Similarly, patients required 106.53 mg [CI -148.20 to -64.86] less diclofenac compared with control/placebo, and had 0.80 [CI -1.07 to -0.54] fewer pain episodes. Visual Analogue Scores were also reduced, -2.43 [CI -3.87 to -0.99]. All formulations of α-antagonists all demonstrated beneficial effects over conservative treatment/placebo. Sensitivity analysis demonstrated significant effects of stone location, stone size and study design. Despite the opposing results of recently published trial, current evidence continues to demonstrate a potential benefit of α-blocker treatment

  8. Antiproliferative effects of β-blockers on human colorectal cancer cells.

    Science.gov (United States)

    Coelho, M; Moz, M; Correia, G; Teixeira, A; Medeiros, R; Ribeiro, L

    2015-05-01

    Colon cancer is the fourth and third most common cancer, respectively in men and women worldwide and its incidence is on the increase. Stress response has been associated with the incidence and development of cancer. The catecholamines (CA), adrenaline (AD) and noradrenaline (NA), are crucial mediators of stress response, exerting their effects through interaction with α- and β-adrenergic receptors (AR). Colon cancer cells express β-AR, and their activation has been implicated in carcinogenesis and tumor progression. Interest concerning the efficacy of β-AR blockers as possible additions to cancer treatment has increased. The aim of this study was to investigate the effect of several AR agonists and β-blockers following cell proliferation of HT-29 cells, a human colon adenocarcinoma cell line. For this purpose, HT-29 cells were incubated in the absence (control) or in the presence of the AR-agonists, AD, NA and isoprenaline (ISO) (0.1-100 µM) for 12 or 24 h. The tested AR agonists revealed proliferative effects on HT-29 cells. In order to study the effect of several β-blockers following proliferation induced by AR activation, the cells were treated with propranolol (PRO; 50 µM), carvedilol (CAR; 5 µM), atenolol (ATE; 50 µM), or ICI 118,551 (ICI; 5 µM) for 45 min prior, and simultaneously, to incubation with each of the AR agonists, AD and ISO, both at 1 and 10 µM. The results suggested that adrenergic activation plays an important role in colon cancer cell proliferation, most probably through β-AR. The β-blockers under study were able to reverse the proliferation induced by AD and ISO, and some of these blockers significantly decreased the proliferation of HT-29 cells. The elucidation of the intracellular pathways involved in CA-induced proliferation of colon cancer cells, and in the reversion of this effect by β-blockers, may contribute to identifying promising strategies in cancer treatment.

  9. Calcium channel blocker enhances beneficial effects of an angiotensin II AT1 receptor blocker against cerebrovascular-renal injury in type 2 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Kazi Rafiq

    Full Text Available Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-A(y mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB disruption, albuminuria, glomerular sclerosis and podocyte injury. These brain and renal injuries were associated with increased gene expression of NADPH oxidase components, NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day reduced blood pressure in saline-drinking KK-A(y mice and attenuated cognitive decline, BBB disruption, glomerular injury and albuminuria, which were associated with a reduction of NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Furthermore, a suppressive dose of azelnidipine (3 mg/kg/day exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associated cerebrovascular-renal protective effects through suppression of NADPH oxidase-dependent oxidative stress in type 2 diabetes.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    OBJECTIVE: To study the initiation of and long-term refill persistency with statins and beta-blockers after acute myocardial infarction (AMI) according to income and education. DESIGN AND SETTING: Linkage of individuals through national registers of hospitalisations, drug dispensation, income...... and education. PARTICIPANTS: 30 078 patients aged 30-74 years surviving first hospitalisation for AMI in Denmark between 1995 and 2001. MAIN OUTCOME MEASURES: Initiation of statin or beta-blocker treatment (out-patient claim of prescriptions within 6 months of discharge) and refill persistency (first break...... in treatment lasting at least 90 days, and re-initiation of treatment after a break). RESULTS: When simultaneously estimating the effect of income and education on initiation of treatment, the effect of education attenuated and a clear income gradient remained for both drugs. Among patients aged 30-64 years...

  12. Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies

    DEFF Research Database (Denmark)

    Bergman, Jorieke E H; Lutke, L Renée; Gans, Rijk O B

    2018-01-01

    the risk of specific congenital anomalies in offspring. METHODS: A population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data...... compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies. RESULTS: The signals from the literature (congenital heart defects, oral clefts, neural......-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm...

  13. Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance.

    Science.gov (United States)

    Cohen-Solal, Alain; Jacobson, Arnold F; Piña, Ileana L

    2017-11-01

    Extent of cardiac sympathetic activation can be estimated from physiological parameters, blood biomarkers, and imaging findings. This study examined the prognostic value of three markers of sympathetic activity and their relationship to beta blocker dose in heart failure patients. A post hoc analysis of 858 heart failure subjects in the ADMIRE-HF trial was performed. Variables related to sympathetic activity were plasma norepinephrine, baseline heart rate, the heart to mediastinum (H/M) ratio of 123 I-mIBG uptake, and beta blocker dose. Univariate and multivariate analyses for occurrence of mortality (all-cause and cardiac) and arrhythmic events were performed. Beta blocker dose was significantly related to age, heart rate, b-type natriuretic peptide (negatively), body mass index, body weight and plasma norepinephrine. Univariate predictors of all-cause and cardiac mortality were baseline heart rate (χ 2  = 4.5, P = 0.029 and χ 2  = 5 .2, P = 0.022, respectively), plasma norepinephrine level (χ 2  = 8.9, P = 0.0006 and χ 2  = 8.6, P = 0.003, respectively), and H/M (χ = 22.4, P heart rate, mean heart rate >67 b.p.m. was associated with significantly higher cardiac mortality. Higher beta blocker dose was associated with lower mortality, but of the variables associated with sympathetic activity examined, cardiac 123 I-mIBG uptake was the most powerful prognostic marker in heart failure patients. Elevated heart rate was associated with greater risk for cardiac death. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  14. Interactions between calcium channel blockers and the anticonvulsants carbamazepine and phenytoin.

    Science.gov (United States)

    Bahls, F H; Ozuna, J; Ritchie, D E

    1991-05-01

    We describe a retrospective analysis of the frequency of adverse interactions between calcium channel blockers and anticonvulsant drugs (phenytoin and carbamazepine) in a series of 43 patients. Ten patients receiving carbamazepine and three patients receiving phenytoin exhibited symptoms or signs of toxicity. Toxicity occurred with both diltiazem and verapamil, but not with nifedipine. These results emphasize the need for careful clinical and laboratory monitoring of patients receiving both classes of medication.

  15. Growth inhibition of human cancer cells in vitro by T-type calcium channel blockers.

    Science.gov (United States)

    Lee, Jae Yeol; Park, Seong Jun; Park, Sung Jun; Lee, Min Joo; Rhim, Hyewhon; Seo, Seon Hee; Kim, Ki-Sun

    2006-10-01

    This paper describes the preliminary biological results that novel T-type calcium channel blockers inhibit the growth of human cancer cells by blocking calcium influx into the cell, based on unknown mechanism on the cell cycle responsible for cellular proliferation. Among the selected compounds from compound library, compound 9c (KYS05041) was identified to be nearly equipotent with Cisplatin against some human cancers in the micromolar range.

  16. Recent developments in HPLC analysis of β-blockers in biological samples.

    Science.gov (United States)

    Saleem, Kishwar; Ali, Imran; Kulsum, Umma; Aboul-Enein, Hassan Y

    2013-09-01

    β-Adrenergic blockers represent a very important class of drugs that are used worldwide for treating various cardiac diseases. The present article describes the state-of-the art of analyses of β-adrenergic blockers using high-performance liquid chromatography (HPLC). Sample preparation techniques such as liquid-liquid extraction, solid-phase extraction and solid-phase microextraction have been discussed, which are essential prior to HPLC analysis. Additionally, applications of liquid chromatography coupled with tandem mass spectrometry are included. HPLC methods have been reported to include 0.6-26 min as the run times and 0.01 ng/mL to 25 µg/mL as detection limits. The most commonly used columns were C18 with various buffers as the mobile phases, along with various organic modifiers. The optimization of HPLC conditions has been discussed. It has been observed that the reported methods are quite satisfactory for the analyses of β-adrenergic blockers in biological samples. Future perspectives in the hyphenation of solid-phase microextraction-nano-liquid chromatography-tandem mass spectrometry have also been highlighted to achieve detections at nanogram and picogram levels. The present article is very useful for academicians, scientists, drug and pharmaceutical personnel and government regulatory authorities.

  17. Management of untreatable ventricular arrhythmias during pharmacologic challenges with sodium channel blockers for suspected Brugada syndrome.

    Science.gov (United States)

    Poli, Stefano; Toniolo, Mauro; Maiani, Massimo; Zanuttini, Davide; Rebellato, Luca; Vendramin, Igor; Dametto, Ermanno; Bernardi, Guglielmo; Bassi, Flavio; Napolitano, Carlo; Livi, Ugolino; Proclemer, Alessandro

    2018-02-01

    Pharmacologic challenge with sodium channel blockers is part of the diagnostic workout in patients with suspected Brugada syndrome. The test is overall considered safe but both ajmaline and flecainide detain well known pro-arrhythmic properties. Moreover, the treatment of patients with life-threatening arrhythmias during these diagnostic procedures is not well defined. Current consensus guidelines suggest to adopt cautious protocols interrupting the sodium channel blockers as soon as any ECG alteration appears. Nevertheless, the risk of life-threatening arrhythmias persists, even adopting a safe and cautious protocol and in absence of major arrhythmic risk factors. The authors revise the main published case studies of sodium channel blockers challenge in adults and in children, and summarize three cases of untreatable ventricular arrhythmias discussing their management. In particular, the role of advanced cardiopulmonary resuscitation with extra-corporeal membrane oxygenation is stressed as it can reveal to be the only reliable lifesaving facility in prolonged cardiac arrest. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  18. β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon.

    Science.gov (United States)

    Richards, John R; Hollander, Judd E; Ramoska, Edward A; Fareed, Fareed N; Sand, I Charles; Izquierdo Gómez, María Manuela; Lange, Richard A

    2017-05-01

    Cocaine abuse remains a significant worldwide health problem. Patients with cardiovascular toxicity from cocaine abuse frequently present to the emergency department for treatment. These patients may be tachycardic, hypertensive, agitated, and have chest pain. Several pharmacological options exist for treatment of cocaine-induced cardiovascular toxicity. For the past 3 decades, the phenomenon of unopposed α-stimulation after β-blocker use in cocaine-positive patients has been cited as an absolute contraindication, despite limited and inconsistent clinical evidence. In this review, the authors of the original studies, case reports, and systematic review in which unopposed α-stimulation was believed to be a factor investigate the pathophysiology, pharmacology, and published evidence behind the unopposed α-stimulation phenomenon. We also investigate other potential explanations for unopposed α-stimulation, including the unique and deleterious pharmacologic properties of cocaine in the absence of β-blockers. The safety and efficacy of the mixed β-/α-blockers labetalol and carvedilol are also discussed in relation to unopposed α-stimulation.

  19. Agile Blocker and Clock Jitter Tolerant Low-Power Frequency Selective Receiver with Energy Harvesting Capability.

    Science.gov (United States)

    Hasan, Abul; Helaoui, Mohamed; Ghannouchi, Fadhel M

    2017-08-29

    In this article, a novel tunable, blocker and clock jitter tolerant, low power, quadrature phase shift frequency selective (QPS-FS) receiver with energy harvesting capability is proposed. The receiver's design embraces and integrates (i) the baseband to radio frequency (RF) impedance translation concept to improve selectivity over that of conventional homodyne receiver topologies and (ii) broadband quadrature phase shift circuitry in the RF path to remove an active multi-phase clock generation circuit in passive mixer (PM) receivers. The use of a single local oscillator clock signal with a passive clock division network improves the receiver's robustness against clock jitter and reduces the source clock frequency by a factor of N, compared to PM receivers using N switches (N≥4). As a consequence, the frequency coverage of the QPS-FS receiver is improved by a factor of N, given a clock source of maximum frequency; and, the power consumption of the whole receiver system can eventually be reduced. The tunable QPS-FS receiver separates the wanted RF band signal from the unwanted blockers/interferers. The desired RF signal is frequency down-converted to baseband, while the undesired blocker/interferer signals are reflected by the receiver, collected and could be energy recycled using an auxiliary energy harvesting device.

  20. Cochrane Corner: Antihypertensive efficacy of beta-1 selective beta blockers for primary hypertension.

    Science.gov (United States)

    Nogueira-Silva, Luís; Marques, Pedro Sousa; Lima, Maria João

    2017-05-01

    Beta blockers are commonly used to treat hypertension. This Cochrane systematic review assessed the effect of beta-1 selective beta blockers on blood pressure (BP), pulse pressure (PP), heart rate (HR) and withdrawal due to adverse effects in patients with primary hypertension. Fifty-six randomized placebo-controlled trials were included, with a total of 7812 patients. These drugs reduced systolic/diastolic BP by 10/8 mmHg, PP by 2 mmHg and HR by 11 bpm; no difference was found between treatment and placebo regarding withdrawal due to adverse effects. Differences in efficacy were observed between the various beta-1 selective beta blockers, which may be due to methodological differences in the trials. The choice of an antihypertensive drug should take into account not only its efficacy in reducing BP but also its tolerability, its efficacy in preventing cardiovascular events, and other factors such as undesirable metabolic effects. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats.

    Science.gov (United States)

    Ludens, J H; Clark, M A; Lawson, J A

    1995-06-01

    Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats were observed. Effects of K+ channel modulation on glomerular filtration rate and electrolyte excretion were studied using the adenosine-triphosphate- (ATP)-sensitive K+ channel blocker 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U-37883A) in conscious rats previously equipped with catheters for clearance studies. In saline-loaded rats, i.v. doses of U-37883A of 1.7, 5.0 and 15 mg/kg increased absolute and fractional Na+ excretion dose-dependently without changing K+ excretion. The glomerular filtration rate remained constant during diuresis. In water-loaded (hypotonic dextrose) rats, free-water clearance studies revealed that the ATP-sensitive K+ channel blocker significantly decreased an index of solute reabsorption (free-water clearance adjusted for chloride clearance) in the diluting segment during peak natriuretic activity. In addition, U-37883A significantly decreased the osmolality of renal papillary interstitial fluid, indicative of an effect in the medullary portion of the diluting segment. Together, these findings suggest that ATP-sensitive K+ channels, possibly those located at the apical boarder, play a pivotal role in Na+ reabsorption in the thick ascending limb of the loop of Henle.

  2. The effect of calcium channel blockers on prevention of preeclampsia in pregnant women with chronic hypertension.

    Science.gov (United States)

    Jiang, N; Liu, Q; Liu, L; Yang, W W; Zeng, Y

    2015-01-01

    Pregnant women with chronic hypertension are at increased risk for complications. This study aims to investigate whether calcium channel blockers plus low dosage aspirin therapy can reduce the incidence of complications during pregnancy with chronic hypertension and improve the prognosis of neonates. From March 2011 to June 2013, 33 patients were selected to join this trial according to the chronic hypertension criteria set by the Preface Bulletin of American College of Obstetricians and Gynecologists, (ACOG). Patients were administrated calcium channel blockers plus low-dosage aspirin and vitamin C. The statistic data of baseline and prognosis from the patients were retrospectively reviewed and compared. Blood pressure of patients was controlled by these medicines with average systolic pressure from 146.3 to 148.7 mmHg and average diastolic pressure from 93.8 to 97.9 mmHg; 39.4% patients complicated mild preeclampsia; however, none of them developed severe preeclampsia or eclampsia, or complicate placental abruption. 30.3% patients delivered at preterm labour; 84.8% patients underwent cesarean section. The neonatal average weight was 3,008 ± 629.6 g, in which seven neonatal weights were less than 2,500 g. All of the neonatal Apgar scores were 9 to 10 at one to five minutes. Small for gestational age (SGA) occurred in five (15%). Calcium channel blockers can improve the outcome of pregnancy women with chronic hypertension to avoid the occurrence of severe pregnancy complication or neonatal morbidity.

  3. L-Carnitine for the treatment of a calcium channel blocker and metformin poisoning.

    Science.gov (United States)

    St-Onge, Maude; Ajmo, Ian; Poirier, Diane; Laliberté, Martin

    2013-09-01

    The object of the current communication is to discuss the theory and the evidence for the use of L-carnitine in calcium channel blocker and metformin poisonings. A 68-year-old male known for hypertension and type II diabetes was admitted to the critical care unit of a community hospital following an overdose of amlodipine and metformin. The patient was intubated, ventilated, and hemodynamically supported with vasopressors. Despite calcium, glucagon, high-dose insulin (HDI), and lipid emulsion for calcium channel blocker and bicarbonate for metabolic acidosis, the patient remained hemodynamically unstable. The patient was considered too unstable to initiate continuous renal replacement therapy; and without access to extracorporeal life support, the administration of L-carnitine was administered as a last resort. One hour after L-carnitine, the norepinephrine requirements started to decrease, the patient began to improve and was subsequently extubated successfully without apparent sequelae in less than 4 days. L-Carnitine combined with HDI may have helped with the calcium channel blocker (CCB) poisoning by decreasing insulin resistance, promoting intracellular glucose transport, facilitating the metabolism of free fatty acids, and increasing calcium channel sensitivity. It may have also stimulated oxidative utilization of glucose instead of converting pyruvate into lactate and contributed to decrease lactate production with metformin poisoning.

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

    Science.gov (United States)

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

    2018-01-25

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

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

    DEFF Research Database (Denmark)

    Winkler, Christine; Hobolth, Lise; Krag, Aleksander

    2011-01-01

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

  6. HIGH SELECTIVE LONG-ACTING Β1-BLOCKER WITH A VASODILATING EFFECT NEBIVOLOL IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    V. P. Lupanov

    2012-01-01

    Full Text Available Review is devoted to the role of modern beta-blocker nebivolol in the treatment of stable ischemic heart disease (IHD. The mode of nebivolol anti-ischemic activity is considered, as well as its use particularities in IHD patients with different concomitant diseases. Nebivolol effects are compared with these of other beta-blockers and other antianginal drugs in terms of angina symptoms reduction, quality of life improvement and decrease in cardiovascular complications risk.

  7. HIGH SELECTIVE LONG-ACTING Β1-BLOCKER WITH A VASODILATING EFFECT NEBIVOLOL IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    V. P. Lupanov

    2015-12-01

    Full Text Available Review is devoted to the role of modern beta-blocker nebivolol in the treatment of stable ischemic heart disease (IHD. The mode of nebivolol anti-ischemic activity is considered, as well as its use particularities in IHD patients with different concomitant diseases. Nebivolol effects are compared with these of other beta-blockers and other antianginal drugs in terms of angina symptoms reduction, quality of life improvement and decrease in cardiovascular complications risk.

  8. Chiral separation of beta-blockers after derivatization with (-)-menthyl chloroformate by reversed-phase high performance liquid chromatography.

    Science.gov (United States)

    Kim, K H; Choi, P W; Hong, S P; Kim, H J

    1999-12-01

    Optimum conditions of chiral derivatization reaction of beta-blockers acebutolol, arotinolol, beta-xolol, bisoprolol, celiprolol, metoprolol and pindolol) with (-)-menthyl chloroformate were investigated for the resolution by HPLC. With more than 30 times molar excess of (-)-menthyl chloroformate chiral derivatization reactions were completed within one hour at room temperature except arotinolol and celiprolol. Diastereomeric derivatives of beta-blockers were well resolved on the ODS column using acetonitrile-methanol-water as a mobile phase.

  9. Barriers to Beta-Blocker Use and Up-Titration Among Patients with Heart Failure with Reduced Ejection Fraction.

    Science.gov (United States)

    Levitan, Emily B; Van Dyke, Melissa K; Loop, Matthew Shane; O'Beirne, Ronan; Safford, Monika M

    2017-12-01

    For patients with heart failure with reduced ejection fraction (HFrEF), guidelines recommend use of beta-blockers with gradual up-titration. However, many patients with HFrEF do not use beta-blockers and up-titration is rare. Our purpose was to identify and rank barriers to beta-blocker use and up-titration from the perspective of primary care physicians. We conducted 4 moderated, structured group discussions among 19 primary care physicians using the nominal group technique; 16 participants also completed a survey. Participants generated lists of barriers to beta-blocker use and up-titration among patients with HFrEF. Each participant had six votes with three votes assigned to the item ranked most important, two to the second most important item, and one to the third most important item. Investigators characterized items into themes. The percentage of available votes was calculated for each theme. Fifteen of 16 participating primary care physicians who completed the survey reported that management of beta-blockers was their responsibility. Treatment/side effects, particularly hypotension, were identified as the most important barrier for beta-blocker use (72% of available votes) followed by polypharmacy (11%), healthcare system barriers (10%), and comorbidities (6%). Barriers to up-titration included treatment/side effects (49% of available votes), patient communication/buy-in (21%), polypharmacy (13%), and healthcare system barriers (8%). Many barriers to guideline concordant use of beta-blockers among patients with HFrEF identified by primary care providers are not readily modifiable. Addressing these barriers may require development, testing, and dissemination of protocols for beta-blocker initiation and up-titration that are safe and appropriate in primary care.

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

    Directory of Open Access Journals (Sweden)

    Laurent Azoulay

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

  11. 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.

  12. Disconnection technique with a bronchial blocker for improving lung deflation: a comparison with a double-lumen tube and bronchial blocker without disconnection.

    Science.gov (United States)

    Yoo, Ji Young; Kim, Dae Hee; Choi, Ho; Kim, Kun; Chae, Yun Jeong; Park, Sung Yong

    2014-08-01

    One-lung ventilation (OLV) is accomplished with a double-lumen tube (DLT) or a bronchial blocker (BB). The authors compared the effectiveness of lung collapse using DLT, BB, and BB with the disconnection technique. Prospective, randomized, blind trial. A university hospital. Fifty-two patients undergoing elective pneumothorax surgery. Patients were assigned randomly to 1 of 3 groups: The DLT group (group 1), the BB group (group 2), and the BB with the disconnection technique group (group 3). The authors modified the disconnection technique in group 3 as follows: (1) turned off the ventilator and opened the adjustable pressure-limiting valve, allowing both lungs to collapse and (2) after loss of the CO2 trace on the capnograph, inflated the blocker cuff and turned on the ventilator, allowing only dependent-lung ventilation. Five and ten minutes after OLV, the degree of lung collapse was assessed by the surgeon, who was blinded to the isolation technique. The quality of lung collapse at 5 and 10 minutes was significantly better in groups 1 and 3 than in group 2. No significant differences were observed for the degree of lung collapse at any time point between groups 1 and 3. The average time for loss of the CO2 trace on the capnograph was 32.3±7.0 seconds in group 3. A BB with spontaneous collapse took longer to deflate and did not provide equivalent surgical exposure to the DLT. The disconnection technique could be helpful to accelerate lung collapse with a BB. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Long-term effects of beta-blocker use on lung function in Japanese patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Oda N

    2017-04-01

    Full Text Available Naohiro Oda,1 Nobuaki Miyahara,1,2 Hirohisa Ichikawa,3 Yasushi Tanimoto,4 Kazuhiro Kajimoto,5 Makoto Sakugawa,6 Haruyuki Kawai,7 Akihiko Taniguchi,1 Daisuke Morichika,1 Mitsune Tanimoto,1 Arihiko Kanehiro,1 Katsuyuki Kiura1 1Department of Allergy and Respiratory Medicine, Okayama University Hospital, 2Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama, 3Department of Respiratory Medicine, KKR Takamatsu Hospital, Takamatsu, 4Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center, Okayama, 5Department of Respiratory Medicine, Kobe Red Cross Hospital, Kobe, 6Department of Respiratory Medicine, Okayama Red Cross Hospital, 7Department of Respiratory Medicine, Okayama Saiseikai Hospital, Okayama, Japan Background: Some recent studies have suggested that beta-blocker use in patients with chronic obstructive pulmonary disease (COPD is associated with a reduction in the frequency of acute exacerbations. However, the long-term effects of beta-blocker use on lung function of COPD patients have hardly been evaluated. Patients and methods: We retrospectively reviewed 31 Japanese COPD patients taking beta-blockers for >1 year and 72 patients not taking them. The association between beta-blocker use and the annual change in forced expiratory volume in 1 second (FEV1 was assessed. Results: At baseline, patient demographic characteristics were as follows: 97 males (mean age 67.0±8.2 years; 32 current smokers; and Global Initiative for Chronic Obstructive Lung disease (GOLD stages I: n=26, II: n=52, III: n=19, and IV: n=6. Patients taking beta-blockers exhibited a significantly lower forced vital capacity (FVC, FEV1, and %FVC, and a more advanced GOLD stage. The mean duration of beta-blocker administration was 2.8±1.7 years. There were no differences in the annual change in FEV1 between patients who did and did not use beta-blockers (-7.6±93.5 mL/year vs -4.7±118.9 m

  14. Efficacy of methylene blue in an experimental model of calcium channel blocker-induced shock.

    Science.gov (United States)

    Jang, David H; Donovan, Sean; Nelson, Lewis S; Bania, Theodore C; Hoffman, Robert S; Chu, Jason

    2015-04-01

    Calcium channel blocker poisonings account for a substantial number of reported deaths from cardiovascular drugs. Although supportive care is the mainstay of treatment, experimental therapies such as high-dose insulin-euglycemia and lipid emulsion have been studied in animal models and used in humans. In the most severe cases, even aggressive care is inadequate and deaths occur. In both experimental models and clinical cases of vasodilatory shock, methylene blue improves hemodynamic measures. It acts as a nitric oxide scavenger and inhibits guanylate cyclase that is responsible for the production of cyclic guanosine monophosphate (cGMP). Excessive cGMP production is associated with refractory vasodilatory shock in sepsis and anaphylaxis. The aim of this study is to determine the efficacy of methylene blue in an animal model of amlodipine-induced shock. Sprague-Dawley rats were anesthetized, ventilated, and instrumented for continuous blood pressure and pulse rate monitoring. The dose of amlodipine that produced death within 60 minutes was 17 mg/kg per hour (LD50). Rats were divided into 2 groups: amlodipine followed by methylene blue or amlodipine followed by normal saline solution, with 15 rats in each group. Rats received methylene blue at 2 mg/kg during 5 minutes or an equivalent amount of normal saline solution in 3 intervals from the start of the protocol: minutes 5, 30, and 60. The animals were observed for a total of 2 hours after the start of the protocol. Mortality risk and survival time were analyzed with Fisher's exact test and Kaplan-Meier survival analysis with the log rank test. Overall, 1 of 15 rats (7%) in the saline solution-treated group survived to 120 minutes compared with 5 of 15 (33%) in the methylene blue-treated group (difference -26%; 95% confidence interval [CI] -54% to 0.3%). The median survival time for the normal saline solution group was 42 minutes (95% CI 28.1 to 55.9 minutes); for the methylene blue group, 109 minutes (95% CI 93.9 to

  15. Costs of tumor necrosis factor blockers per treated patient using real-world drug data in a managed care population.

    Science.gov (United States)

    Schabert, Vernon F; Watson, Crystal; Joseph, George J; Iversen, Paige; Burudpakdee, Chakkarin; Harrison, David J

    2013-10-01

    Several anti-inflammatory biologic medications are available in the United States for the treatment of moderate-to-severe rheumatoid arthritis, moderate-to-severe psoriasis, psoriatic arthritis, or ankylosing spondylitis. The tumor necrosis factor (TNF) blockers etanercept, adalimumab, and infliximab are approved for use in adults with any of these conditions, but predicting the annual costs of TNF-blocker treatment is complex due to differences in dosing schedules, treatment gaps, switching between TNF blockers, and dose escalation over time. To estimate the annual cost per treated patient from the payer perspective for etanercept, adalimumab, or infliximab in adults with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Adults in the IMS LifeLink Health Plan Claims Database were analyzed if they had at least 1 claim for etanercept, adalimumab, or infliximab between February 1, 2008, and July 5, 2010, and were continuously enrolled for at least 180 days before (pre-index period) through 360 days after the index claim (the first TNF-blocker claim after 6 months of continuous enrollment in the study period). Patients had a diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis, or a combination of these conditions, in the pre-index period. Cost was based on dose and price using April 2012 wholesale acquisition cost. Costs of administration were included for the first subcutaneous dose (etanercept or adalimumab) for new patients and for every intravenous dose (infliximab). Total TNF-blocker drug and administration costs, including nonindex TNF-blocker costs among patients who switched treatments, were divided by number of patients to yield cost per treated patient for each index TNF blocker. Subgroup analyses included cost by condition and cost for patients who were new to TNF-blocker treatment (no index TNF-blocker claim in the pre-index period) or continuing TNF-blocker treatment. Of the 30

  16. Old Friends With New Faces: Are Sodium Channel Blockers the Future of Adjunct Pain Medication Management?

    Science.gov (United States)

    Thomas, Ashley M; Atkinson, Timothy J

    2018-01-01

    Providers are being asked to decrease the emphasis and overutilization of long-term opioid therapy, but many are left without proper guidance on appropriate utilization of nonopioid therapies. Furthermore, therapeutic options are quite limited and many providers lack confidence in distinguishing available alternatives. When first-line therapy has failed in a patient, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy. To choose among alternative agents, an understanding of pharmacology, pharmacokinetics, and efficacy in targeting various pain conditions is necessary. This article focuses on the use of the carboxamide class of sodium channel blockers (carbamazepine, oxcarbazepine, eslicarbazepine) for adjunct pain medication management including research updates in pharmacology, pharmacokinetics, and current evidence for pain along with promising areas of research. It is an evidence update for clinical use of sodium channel blockers, clarifies misconceptions regarding their use, and highlights emerging research for improved pain targets that justifies additional study. We performed a complete review of the literature using the search terms, "oxcarbazepine," "carbamazepine," and "eslicarbazepine" in conjunction with "pharmacokinetics," "adverse effects," "pharmacology," "voltage-gated sodium channel subtype," "neuropathic pain," "inflammatory pain," "metabolism," "epoxide metabolite formation," "drug interactions," "CYP450 interactions," "pain phenotype," and "chronic pain management." Databases searched included PubMed and Google Scholar. Package inserts were used for drug structure illustration, adverse reactions, and bioavailability. Pharmacology and pharmacokinetic data were taken from randomized controlled trials evaluating this area as well as in vitro published results. For validity, only peer-reviewed literature was included. Evidence for sodium channel blockers in chronic pain management was limited. This review focuses

  17. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

    Science.gov (United States)

    Montoya, Alexa; Amaya, Clarissa N; Belmont, Andres; Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T; Aguilera, Renato J; Dickerson, Erin B; Torabi, Alireza; Dwivedi, Alok K; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A; Nahleh, Zeina

    2017-01-24

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

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

    Science.gov (United States)

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

    2015-09-01

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

  19. Has beta-blocker use increased in patients with heart failure in internal medicine settings? Prognostic implications: RICA registry.

    Science.gov (United States)

    González-García, Andrés; Montero Pérez-Barquero, Manuel; Formiga, Francesc; González-Juanatey, José R; Quesada, M Angustias; Epelde, Francisco; Oropesa, Roberto; Díez-Manglano, Jesús; Cerqueiro, José M; Manzano, Luis

    2014-03-01

    Underuse of beta-blockers has been reported in elderly patients with heart failure. The aim of this study was to evaluate the current prescription of beta-blockers in the internal medicine setting, and its association with morbidity and mortality in heart failure patients. The information analyzed was obtained from a prospective cohort of patients hospitalized for heart failure (RICA registry] database, patients included from March 2008 to September 2011) with at least one year of follow-up. We investigated the percentage of patients prescribed beta-blockers at hospital discharge, and at 3 and 12 months, and the relationship of beta-blocker use with mortality and readmissions for heart failure. Patients with significant valve disease were excluded. A total of 515 patients were analyzed (53.5% women), with a mean age of 77.1 (8.7) years. Beta-blockers were prescribed in 62.1% of patients at discharge. A similar percentage was found at 3 months (65.6%) and 12 months (67.9%) after discharge. All-cause mortality and the composite of all-cause mortality and readmission for heart failure were significantly lower in patients treated with beta-blockers (hazard ratio=0.59, 95% confidence interval, 0.41-0.84 vs hazard ratio=0.64, 95% confidence interval, 0.49-0.83). This decrease in mortality was maintained after adjusting by age, sex, ejection fraction, functional class, comorbidities, and concomitant treatment. The findings of this study indicate that beta-blocker use is increasing in heart failure patients (mainly elderly) treated in the internal medicine setting, and suggest that the use of these drugs is associated with a reduction in clinical events. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  20. α-adrenergic blockers for the treatment of lower-urinary-tract symptoms and dysfunction in women.

    Science.gov (United States)

    Boyd, Katie; Hilas, Olga

    2014-06-01

    To evaluate the efficacy and safety of α-adrenergic blockers in the treatment of female lower-urinary-tract symptoms and dysfunction. Literature searches were conducted using EMBASE (1974 to January 2014), International Pharmaceutical Abstracts (1970 to January 2014), and MEDLINE (1946 to January 2014) to identify clinical trials evaluating the effects of α-adrenergic blockers in the treatment of women with lower-urinary-tract dysfunction. Bibliographies from relevant research articles were also reviewed for inclusion. All original research articles available in the English language were identified from the data sources. Primary literature evaluating outcomes related to urinary dysfunction and associated symptoms in women were included in this review. Articles describing the use of α-adrenergic blockers in other medical conditions or in men were excluded. A total of 15 clinical studies were identified and evaluated. Many studies showed an improvement in female lower-urinary-tract symptoms and dysfunction using α-adrenergic blockers. Most studies also reported adverse drug events of α-adrenergic blockers such as dizziness and hypotension. However, limitations of the studies conducted to date include small sample sizes, inconsistent study designs, and short duration of therapy. The role of α-adrenergic blockers in the treatment of urinary dysfunction and associated symptoms in women remains unclear. The majority of evidence suggests that these agents may have a place in therapy for female lower-urinary-tract symptoms and/or bladder outlet obstruction; however, data are conflicting. Clinicians should be aware of the potential clinical benefits but also recognize the potential adverse drug effects of α-adrenergic blockers.

  1. 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.

  2. Detection of low-level DNA mutation by ARMS-blocker-Tm PCR.

    Science.gov (United States)

    Qu, Shoufang; Liu, Licheng; Gan, Shuzhen; Feng, Huahua; Zhao, Jingyin; Zhao, Jing; Liu, Qi; Gao, Shangxiang; Chen, Weijun; Wang, Mengzhao; Jiang, Yongqiang; Huang, Jie

    2016-02-01

    Low-level DNA mutations play important roles in cancer prognosis and treatment. However, most existing methods for the detection of low-level DNA mutations are insufficient for clinical applications because of the high background of wild-type DNA. In this study, a novel assay based on Tm-dependent inhibition of wild type template amplification was developed. The defining characteristic of this assay is an additional annealing step was introduced into the ARMS-blocker PCR. The temperature of this additional annealing step is equal to the Tm of the blocker. Due to this additional annealing step, the blocker can preferentially and specifically bind the wild-type DNA. Thus, the inhibition of wild type template is realized and the mutant DNA is enriched. The sensitivity of this assay was between 10(-4) and 10(-5), which is approximately 5 to 10 times greater than the sensitivity of the assay without the additional annealing step. To evaluate the performance of this assay in detecting K-ras mutation, we analyzed 100 formalin-fixed paraffin-embedded (FFPE) specimens from colorectal cancer patients using this new assay and Sanger sequencing. Of the clinical samples, 27 samples were positive for K-ras mutation by both methods. Our results indicated that this new assay is a highly selective, convenient, and economical method for detecting rare mutations in the presence of higher concentrations of wild-type DNA. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  3. Covered transjugular intrahepatic portosystemic shunt versus endoscopic therapy + β-blocker for prevention of variceal rebleeding.

    Science.gov (United States)

    Holster, I Lisanne; Tjwa, Eric T T L; Moelker, Adriaan; Wils, Alexandra; Hansen, Bettina E; Vermeijden, J Reinoud; Scholten, Pieter; van Hoek, Bart; Nicolai, Jan J; Kuipers, Ernst J; Pattynama, Peter M T; van Buuren, Henk R

    2016-02-01

    Gastroesophageal variceal bleeding in patients with cirrhosis is associated with significant morbidity and mortality, as well as a high rebleeding risk. Limited data are available on the role of transjugular intrahepatic portosystemic shunt (TIPS) with covered stents in patients receiving standard endoscopic, vasoactive, and antibiotic treatment. In this multicenter randomized trial, long-term endoscopic variceal ligation (EVL) or glue injection + β-blocker treatment was compared with TIPS placement in 72 patients with a first or second episode of gastric and/or esophageal variceal bleeding, after hemodynamic stabilization upon endoscopic, vasoactive, and antibiotic treatment. Randomization was stratified according to Child-Pugh score. Kaplan-Meier (event-free) survival estimates were used for the endpoints rebleeding, death, treatment failure, and hepatic encephalopathy. During a median follow-up of 23 months, 10 (29%) of 35 patients in the endoscopy + β-blocker group, as compared to 0 of 37 (0%) patients in the TIPS group, developed variceal rebleeding (P = 0.001). Mortality (TIPS 32% vs. endoscopy 26%; P = 0.418) and treatment failure (TIPS 38% vs. endoscopy 34%; P = 0.685) did not differ between groups. Early hepatic encephalopathy (within 1 year) was significantly more frequent in the TIPS group (35% vs. 14%; P = 0.035), but during long-term follow-up this difference diminished (38% vs. 23%; P = 0.121). In unselected patients with cirrhosis, who underwent successful endoscopic hemostasis for variceal bleeding, covered TIPS was superior to EVL + β-blocker for reduction of variceal rebleeding, but did not improve survival. TIPS was associated with higher rates of early hepatic encephalopathy. © 2015 by the American Association for the Study of Liver Diseases.

  4. Left Ventricular Remodeling after Myocardial Infarction: Characterization of a Swine Model on β-Blocker Therapy

    Science.gov (United States)

    Angeli, Franca S; Shapiro, Mia; Amabile, Nicolas; Orcino, Gina; Smith, Charles S; Tacy, Theresa; Boyle, Andrew J; Chatterjee, Kanu; Glantz, Stanton A; Grossman, William; Yeghiazarians, Yerem

    2009-01-01

    Current guidelines recommend β blockers for patients after myocardial infarction (MI). Novel therapies for heart failure should be tested in combination with this medication before entering clinical trials. In this methodologic study, we sought to describe the time course of systolic and diastolic parameters of cardiac performance over a 6-wk period in closed-chest model of swine MI treated with a β blocker. Myocardial infarction in pigs (n = 10) was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Echocardiography and pressure–volume data were collected before and at 1 and 6 wk after MI; histopathology was assessed at 6 wk. Left-ventricular (LV) volume increased significantly over 6 wk, with significant decreases in ejection fraction, wall motion index, stroke work, rate of pressure development (dP/dtmax), preload recruitable stroke work, and mechanical efficiency. Impairment of diastolic function was manifested by a significant increase in the exponential β coefficient of the LV end-diastolic pressure–volume relation and reduction of LV pressure decay. At 6 wk, histopathologic analysis showed that the size of the infarct area was 16.3% ± 4.4%, and the LV mass and myocyte cross-sectional area in both the infarct border and remote zones were increased compared with those of noninfarcted pigs (n = 5). These findings suggest a dynamic pattern of remodeling over time in a closed-chest ischemia–reperfusion swine model of acute MI on β-blocker therapy and may guide future studies. PMID:19619418

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

    Science.gov (United States)

    Linsdell, Paul

    2014-02-26

    Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel causes cystic fibrosis, while inappropriate activity of this channel occurs in secretory diarrhea and polycystic kidney disease. Drugs that interact directly with CFTR are therefore of interest in the treatment of a number of disease states. This review focuses on one class of small molecules that interacts directly with CFTR, namely inhibitors that act by directly blocking chloride movement through the open channel pore. In theory such compounds could be of use in the treatment of diarrhea and polycystic kidney disease, however in practice all known substances acting by this mechanism to inhibit CFTR function lack either the potency or specificity for in vivo use. Nevertheless, this theoretical pharmacological usefulness set the scene for the development of more potent, specific CFTR inhibitors. Biophysically, open channel blockers have proven most useful as experimental probes of the structure and function of the CFTR chloride channel pore. Most importantly, the use of these blockers has been fundamental in developing a functional model of the pore that includes a wide inner vestibule that uses positively charged amino acid side chains to attract both permeant and blocking anions from the cell cytoplasm. CFTR channels are also subject to this kind of blocking action by endogenous anions present in the cell cytoplasm, and recently this blocking effect has been suggested to play a role in the physiological control of CFTR channel function, in particular as a novel mechanism linking CFTR function dynamically to the composition of epithelial cell secretions. It has also been suggested that future drugs could target this same pathway as a way of pharmacologically increasing CFTR activity in cystic fibrosis. Studying open channel blockers and their mechanisms of action has resulted in significant advances in our understanding of CFTR as a pharmacological target in disease

  6. Relationships of beta-blockers and anxiolytics intake and salivary secretion, masticatory performance and taste perception.

    Science.gov (United States)

    de Matos, Leandro Faria; Pereira, Stela Márcia; Kaminagakura, Estela; Marques, Leandro Silva; Pereira, Cássio Vicente; van der Bilt, Andries; Pereira, Luciano José

    2010-02-01

    Assess the influence of salivary flow on physiological parameters of the stomatognathic system in patients who take beta-blockers or anxiolytic medications. Sixty patients were divided into three groups based on the following criteria: Group 1, control (n=20; no use of medication); Group 2, use of antihypertensive beta-blockers (n=20); and Group 3, use of benzodiazepine anxiolytics (n=20). Salivary flow was assessed by determining stimulated and non-stimulated flow/minute. The quantification of the sense of taste was determined on a visual analogue scale (VAS) using solutions of 0.9% NaCl (salty), 50% sucrose (sweet), 20% unsweetened coffee (bitter) and 4.2% vinegar (sour). The DMFT index (number of decayed/missing/filled teeth) was determined by a calibrated examination, following the criteria of the World Health Organization (WHO). Masticatory performance was assessed with an Optosil comminution test and Rosim-Ramler equation. The results did not reveal a significant correlation between salivary flow and masticatory performance (p>0.05). We observed significant decreased non-stimulated salivary flow for Group 2 (p=0.05) when compared to controls. However, taste perception was not influenced by salivary secretion amongst groups. Furthermore, we observed a significant negative correlation between non-stimulated salivary flow and DMFT in Group 1 (p=0.02; r=-0.52). Patients under beta-blockers therapy presented reduced non-stimulated salivary flow when compared to controls, without influencing the sense of taste or masticatory performance. The use of anxiolytics did not affect salivary flow and taste perception in the studied sample. Copyright 2009 Elsevier Ltd. All rights reserved.

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

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    Zimlichman R

    2011-12-01

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

  8. Effects of prostatic inflammation on LUTS and alpha blocker treatment outcomes

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    Ha Na Lee

    2014-06-01

    Full Text Available Purpose To evaluate the association between prostatic inflammation and lower urinary tract symptoms (LUTS, and to identify the effects of prostatic inflammation on the treatment with an alpha blocker. Materials and Methods 111 Participants who were aged ≥ 50 years, the presence of LUTS (maximal flow rate < 20 m/s, IPSS ≥ 11, and an elevated PSA level (3-20ng/mL were treated with tamsulosin 0.2mg once daily for 3 months after prostate biopsies. Prostatic inflammation was scored as none (0, mild (I, moderate (II, or marked (III. LUTS parameters including urine flow rates, IPSS, PSA, and prostate volume were evaluated. Results Inflammation grading resulted in 25, 60, and 26 patients that were grade 0, I, and II, respectively. Lower grade inflammation was related to higher urine flow rate at baseline. Patients with higher inflammation grades had larger prostate volumes, larger total and transitional zone volumes, and higher PSA levels. Overall, urine flow rates and residual urine volume were improved after 3 months of alpha blocker therapy. Eighty percent of patients with grade 0 inflammation, 73% of patients with grade I inflammation, and 92.3% of patients with grade II inflammation showed improvement of LUTS after treatment. Longer duration of treatment was related to a decreased chance of improvement of LUTS. Patients with increased IPSS voiding subscales could be predictive of improvement of LUTS. Conclusions Patients with high grade inflammation had lower flow rates and higher prostatic volumes than patients with low grade inflammation. Inflammation grade did not affect the outcomes of alpha blocker treatment.

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

    Science.gov (United States)

    Yan, Rui; Page, Jessica C.

    2015-01-01

    Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K+ channels due to myelin damage leads to conduction block, and K+ channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K+ channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K+ channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases. PMID:26581866

  10. Calcium channel blockers in the management of hypertension in the elderly.

    Science.gov (United States)

    Caballero-Gonzalez, Francisco J

    2015-01-01

    The aging population is rapidly increasing, and is mainly due to medical advances and the control of chronic diseases, with a real worldwide increase in the elderly population. Special emphasis has been placed on the management of hypertension in the geriatric patient, since its long-term benefits have been shown to prevent both cerebral and cardiac infarctions. Calcium channel blockers have been shown to be effective in this condition in the elderly. Their success depends on their mechanism of action, as well as on the physiological changes observed, and on the aging process itself, which include cardiac hypertrophy, calcification of cardiac valves, and a decrease in the excitation-conduction system. There is thickening of the tunica intima of the arteries, and the production of nitric oxide at cellular level decreases with age, along with an increase in endothelin 1, which leads to vascular endothelium dysfunction. In the kidneys, there is a decrease in prostacyclin, endothelial hyperpolarization factor, as well as the Klotho anti-aging protein, which leads to an increase in blood pressure. Calcium channel blocker drugs have been shown to be effective in any age group for the management of hypertension, and are safe in the elderly patients. These drugs block L-type calcium channels, with the long-acting or latest generation dihydropyridines being the most effective of this group. Several studies, including SYST-EUR2, NORDIL, and STOP-2, have demonstrated the effectiveness of these drugs in the geriatric patient. The prescribing of long-acting calcium channel blocker drugs in a single dose is the most recommended. The safety in the use of this drug group has been demonstrated in the treatment of hypertension in the elderly patient, with a level of effectiveness similar to other widely used drugs.

  11. The β-blocker Nebivolol Is a GRK/β-arrestin biased agonist.

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    Catherine E Erickson

    Full Text Available Nebivolol, a third generation β-adrenoceptor (β-AR antagonist (β-blocker, causes vasodilation by inducing nitric oxide (NO production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the controversy regarding the pharmacological action of nebivolol. Carvedilol is another β-blocker that induces NO production. A prominent pharmacological mechanism of carvedilol is biased agonism that is independent of Gαs and involves G protein-coupled receptor kinase (GRK/β-arrestin signaling with downstream activation of the epidermal growth factor receptor (EGFR and extracellular signal-regulated kinase (ERK. Due to the pharmacological similarities between nebivolol and carvedilol, we hypothesized that nebivolol is also a GRK/β-arrestin biased agonist. We tested this hypothesis utilizing mouse embryonic fibroblasts (MEFs that solely express β2-ARs, and HL-1 cardiac myocytes that express β1- and β2-ARs and no detectable β3-ARs. We confirmed previous reports that nebivolol does not significantly alter cAMP levels and thus is not a classical agonist. Moreover, in both cell types, nebivolol induced rapid internalization of β-ARs indicating that nebivolol is also not a classical β-blocker. Furthermore, nebivolol treatment resulted in a time-dependent phosphorylation of ERK that was indistinguishable from carvedilol and similar in duration, but not amplitude, to isoproterenol. Nebivolol-mediated phosphorylation of ERK was sensitive to propranolol (non-selective β-AR-blocker, AG1478 (EGFR inhibitor, indicating that the signaling emanates from β-ARs and involves the EGFR. Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. Additionally, nebivolol induced redistribution of β-arrestin 2 from a diffuse staining pattern into more intense punctate spots. We conclude that nebivolol is a β2

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

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Sørensen, Flemming Steen

    2011-01-01

    whereas QSAR and classification models provide a faster assessment and detection of hERG-related drug toxicity, limitation on the applicability domain of the current models and integration of data from diverse in vitro approaches are still issues to challenge.Therefore, this review will emphasize...... on current methods to predict hERG blockers and the need of consistent data to improve the quality and performance of the in silico models. Finally, integration of network-based analysis on drugs inducing potentially long-QT syndrome and arrhythmia will be discussed as a new perspective for a better...

  13. 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.

  14. Non-selective beta-blockers may reduce risk of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Thiele, Maja; Albillos, Agustín; Abazi, Rozeta

    2015-01-01

    BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are used in patients with cirrhosis and oesophageal varices. Experimental data suggest that NSBB inhibit angiogenesis and reduce bacterial translocation, which may prevent hepatocellular carcinoma (HCC). We therefore assessed the effect of NSBB.......052 to -0.001; number needed to treat 38 patients). There was no heterogeneity (I(2) = 7%) or evidence of small study effects (Eggers P = 0.402). The result was not confirmed in sequential analysis, which suggested that 3719 patients were needed to achieve the required information size. NSBB did not reduce...

  15. Cardiac arrest after esmolol administration: a review of acute beta-blocker toxicity.

    Science.gov (United States)

    Litman, R S; Zerngast, B A

    1996-10-01

    An 11-year-old, 25-kg girl with congenital myelomeningocele was scheduled for posterior spinal fusion because of progressive scoliosis. After induction of general anesthesia and administration of a standard dose of intravenous esmolol hydrochloride, her cardiac rhythm progressed to asystole. Although given ephedrine, epinephrine, and atropine sulfate, the patient's normal heart rhythm could not be restored until calcium chloride was administered. A review of the medical literature indicates that the optimal treatment for acute beta-blocker toxicity is intravenous glucagon. Calcium administration should also be considered. Acute esmolol toxicity may be self-limiting because of its extremely short half-life.

  16. Are there any positive effects of TNF-alpha blockers on bone metabolism?

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    A. Sulli

    2011-09-01

    Full Text Available Secondary osteoporosis (OP is a well-recognized complication of rheumatoid arthritis (RA. Treatment with TNF-a blockers, might influence bone metabolism and prevent structural bone damage in RA, in particular at the periarticular regions. Objective: To assess the influence of anti-TNF-a therapy, on bone metabolism in RA patients. 36 RA patients were treated with stable therapy of prednisone (7.5 mg/day and methotrexate (MTX=10 mg/week. Nine of these RA patients further received etanercept (25 mg, twice/weekly and eleven infliximab (3mg/kg on 0, 2, 6, and every 8 weeks thereafter. A control group included 16 RA patients only with stable therapy (some dosage of prednisone and MTX. Quantitative Ultrasound (QUS bone densitometry was obtained at the metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS device (IGEA, Carpi, Italy. Bone mineral density (BMD of the hip and lumbar spine were performed with a densitometer ( Lunar Prodigy, GE, USA at baseline and after 12 months. Soluble bone turnover markers [osteocalcin (OC, bone alkaline phospatase (ALP deoxypyridinoline/creatinine ratio (Dpd/Cr and cross-linked N-telopeptide of type I collagen / creatinine ratio (NTx/Cr] were measured using ELISA tests. Results: AD-SoS values were found increased by +4.55% after 12 months of treatment in the RA patients treated with anti-TNF-a therapy. On the contrary, the Ad-SoS levels decreased by -4.48% during the same period in the control RA group. BMD increased by +3.64% at lumbar spine and +2.90% at the hip (both p<0.001 in TNF-a blockers-treated patients and decreased by -2.89% and -3.10% (both p<0.001, respectively at lumbar spine and at the hip in RA patients without anti-TNF-a therapy. In RA patients treated with TNF-a blockers, OC and bone ALP levels were found significantly increased (p<0.01 and Dpd/Cr or NTx/Cr levels were found significantly decreased (p<0.01 at 12 months when compared to baseline values. Conclusion: During 12

  17. Intraoperative Extracorporeal Carbon Dioxide Removal During Apneic Oxygenation with an EZ-Blocker in Tracheal Surgery.

    Science.gov (United States)

    Rispoli, Marco; Nespoli, Moana Rossella; Mattiacci, Dario Maria; Esposito, Marianna; Corcione, Antonio; Buono, Salvatore

    2016-06-01

    Tracheal surgery requires continued innovation to manage the anesthetic during an open airway phase. A common approach is apneic oxygenation with continuous oxygen flow, but the lack of effective ventilation causes hypercapnia, with respiratory acidosis. We used extracorporeal carbon dioxide removal for intraoperative decapneization during apneic oxygenation in a 64-year-old woman who was scheduled for tracheal surgery because of tracheal stenosis caused by long-term intubation. Our findings demonstrate that even after 40 minutes of total apnea, using an EZ-blocker for oxygenation and external decapneization, hemodynamic and gas exchange variables never demonstrated any dangerous alterations.

  18. Association of β-Blockers With Functional Outcomes, Death, and Rehospitalization in Older Nursing Home Residents After Acute Myocardial Infarction.

    Science.gov (United States)

    Steinman, Michael A; Zullo, Andrew R; Lee, Yoojin; Daiello, Lori A; Boscardin, W John; Dore, David D; Gan, Siqi; Fung, Kathy; Lee, Sei J; Komaiko, Kiya D R; Mor, Vincent

    2017-02-01

    Although β-blockers are a mainstay of treatment after acute myocardial infarction (AMI), these medications are commonly not prescribed for older nursing home residents after AMI, in part owing to concerns about potential functional harms and uncertainty of benefit. To study the association of β-blockers after AMI with functional decline, mortality, and rehospitalization among long-stay nursing home residents 65 years or older. This cohort study of nursing home residents with AMI from May 1, 2007, to March 31, 2010, used national data from the Minimum Data Set, version 2.0, and Medicare Parts A and D. Individuals with β-blocker use before AMI were excluded. Propensity score-based methods were used to compare outcomes in people who did vs did not initiate β-blocker therapy after AMI hospitalization. Functional decline, death, and rehospitalization in the first 90 days after AMI. Functional status was measured using the Morris scale of independence in activities of daily living. The initial cohort of 15 720 patients (11 140 women [70.9%] and 4580 men [29.1%]; mean [SD] age, 83 [8] years) included 8953 new β-blocker users and 6767 nonusers. The propensity-matched cohort included 5496 new users of β-blockers and an equal number of nonusers for a total cohort of 10 992 participants (7788 women [70.9%]; 3204 men [29.1%]; mean [SD] age, 84 [8] years). Users of β-blockers were more likely than nonusers to experience functional decline (odds ratio [OR], 1.14; 95% CI, 1.02-1.28), with a number needed to harm of 52 (95% CI, 32-141). Conversely, β-blocker users were less likely than nonusers to die (hazard ratio [HR], 0.74; 95% CI, 0.67-0.83) and had similar rates of rehospitalization (HR, 1.06; 95% CI, 0.98-1.14). Nursing home residents with moderate or severe cognitive impairment or severe functional dependency were particularly likely to experience functional decline from β-blockers (OR, 1.34; 95% CI, 1.11-1.61 and OR, 1.32; 95% CI, 1.10-1.59, respectively

  19. Impact of selective and nonselective beta-blockers on the risk of severe exacerbations in patients with COPD

    Directory of Open Access Journals (Sweden)

    Huang YL

    2017-10-01

    Full Text Available Yueh Lan Huang,1 Chih-Cheng Lai,2 Ya-Hui Wang,3 Cheng-Yi Wang,1 Jen-Yu Wang,1 Hao-Chien Wang,4 Chong-Jen Yu,4 Likwang Chen5 On behalf of the Taiwan Clinical Trial Consortium for Respiratory Diseases (TCORE 1Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, 2Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, 3Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, 4Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, 5Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan Background: There is conflicting information regarding the effects of selective and nonselective beta-blocker treatment in patients with COPD.Participants and methods: This nested case–control study used the Taiwan National Health Insurance Research Database. We included COPD patients who used inhalation steroid and beta-blockers between 1998 and 2010. From this cohort, there were 16,067 patients with severe exacerbations included in the analysis and 55,970 controls matched on age, sex, COPD diagnosis year, and beta-blockers treatment duration by risk set sampling.Results: For the selective beta-blocker users, the current users had a lower risk of severe exacerbations than the nonusers (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.85–0.96. In contrast, for the nonselective beta-blocker users, the current users had a higher risk of severe acute exacerbations than the nonusers (OR, 1.21; 95% CI, 1.14–1.27. A higher risk of severe exacerbation during increasing mean daily dose or within about the initial 300 days was found in nonselective beta-blockers, but not in selective beta-blockers. One selective beta-blocker, betaxolol, had a

  20. Improving documentation of a beta-blocker quality measure through an anesthesia information management system and real-time notification of documentation errors.

    Science.gov (United States)

    Nair, Bala G; Peterson, Gene N; Newman, Shu-Fang; Wu, Wei-Ying; Kolios-Morris, Vickie; Schwid, Howard A

    2012-06-01

    Continuation of perioperative beta-blockers for surgical patients who are receiving beta-blockers prior to arrival for surgery is an important quality measure (SCIP-Card-2). For this measure to be considered successful, name, date, and time of the perioperative beta-blocker must be documented. Alternately, if the beta-blocker is not given, the medical reason for not administering must be documented. Before the study was conducted, the institution lacked a highly reliable process to document the date and time of self-administration of beta-blockers prior to hospital admission. Because of this, compliance with the beta-blocker quality measure was poor (-65%). To improve this measure, the anesthesia care team was made responsible for documenting perioperative beta-blockade. Clear documentation guidelines were outlined, and an electronic Anesthesia Information Management System (AIMS) was configured to facilitate complete documentation of the beta-blocker quality measure. In addition, real-time electronic alerts were generated using Smart Anesthesia Messenger (SAM), an internally developed decision-support system, to notify users concerning incomplete beta-blocker documentation. Weekly compliance for perioperative beta-blocker documentation before the study was 65.8 +/- 16.6%, which served as the baseline value. When the anesthesia care team started documenting perioperative beta-blocker in AIMS, compliance was 60.5 +/- 8.6% (p = .677 as compared with baseline). Electronic alerts with SAM improved documentation compliance to 94.6 +/- 3.5% (p < .001 as compared with baseline). To achieve high compliance for the beta-blocker measure, it is essential to (1) clearly assign a medical team to perform beta-blocker documentation and (2) enhance features in the electronic medical systems to alert the user concerning incomplete documentation.

  1. Coronary computed tomography angiography - Tolerability of β-blockers and contrast media, and temporal changes in radiation dose

    DEFF Research Database (Denmark)

    Pedersen, Charlotte; Thomsen, Camilla F; Hosbond, Susanne Elisabeth

    2014-01-01

    Abstract Objective: To determine the risk of administration of β-blockers, contrast induced nephropathy (CIN) and trend in x-rays use, during coronary computed tomography angiography (CCTA). Methods: A total of 416 patients were referred for elective CCTA. To achieve a resting heart rate below 60.......0001. Conclusions: In terms of side effects to β-blockers and contrast media, there were no short term complications to CCTA. Furthermore the radiation dose was dramatically diminished over the last three years.......Abstract Objective: To determine the risk of administration of β-blockers, contrast induced nephropathy (CIN) and trend in x-rays use, during coronary computed tomography angiography (CCTA). Methods: A total of 416 patients were referred for elective CCTA. To achieve a resting heart rate below 60...... beats per minute oral and / or intravenously β-blockers were administered. Information was collected from patients on the adverse effects of β-blockers in the form of questionnaires. S-creatinine and estimated GFR (eGFR) were measured before and after contrast enhanced CCTA. Radiation exposure...

  2. Effects of beta-adrenergic blockers with different ancillary properties on lipid peroxidation in hyperthyroid rat cardiac muscle.

    Science.gov (United States)

    Asayama, K; Dobashi, K; Hayashibe, H; Kato, K

    1989-10-01

    To determine whether beta-blockade protects rat heart against thyroxine (T4)-induced accelelation of lipid peroxidation, in vivo effects of 3 beta-blockers with different ancillary properties on the mitochondrial oxidative enzyme, antioxidant enzymes and lipid peroxide were investigated. The rats were rendered hyperthyroid by adding T4 to their drinking water for 3 weeks and were treated simultaneously with either carteolol (a blocker with partial agonist activity; 30 mg/kg/day), atenolol (50 mg/kg/day) or arotinolol (a blocker with weak alpha-blocking action; 50 mg/kg/day). The T4-induced tachycardia was alleviated completely by either atenolol or arotinolol, but only partially by carteolol. Cytochrome c oxidase activity in the heart muscle was increased by T4 with a parallel increase in manganese (mitochondrial) superoxide dismutase. Atenolol, but neither carteolol nor arotinolol, suppressed this increase. Similarly, the T4-induced acceleration of lipid peroxidation was suppressed by atenolol alone. Glutathione peroxidase was markedly decreased, and both copper zinc (cytosolic) superoxide dismutase and catalase were also decreased or tended to be decreased by T4. The levels of these 3 enzymes were only minimally affected by the beta-blocker treatments. These results suggest that beta-blockade suppresses mitochondrial hypermetabolism and protects heart muscle against oxidative stress in hyperthyroidism, and that the ancillary properties of beta-blockers such as partial agonist activity and alpha-blocking action negate the protection.

  3. [Progress in sodium channelopathies and biological functions of voltage-gated sodium channel blockers].

    Science.gov (United States)

    Wang, Hongyan; Gou, Meng; Xiao, Rong; Li, Qingwei

    2014-06-01

    Voltage-gated sodium channels (VGSCs), which are widely distributed in the excitable cells, are the primary mediators of electrical signal amplification and propagation. They play important roles in the excitative conduction of the neurons and cardiac muscle cells. The abnormalities of the structures and functions of VGSCs can change the excitability of the cells, resulting in a variety of diseases such as neuropathic pain, epilepsy and arrhythmia. At present, some voltage-gated sodium channel blockers are used for treating those diseases. In the recent years, several neurotoxins have been purified from the venom of the animals, which could inhibit the current of the voltage-gated sodium channels. Usually, these neurotoxins are compounds or small peptides that have been further designed and modified for targeted drugs of sodium channelopathies in the clinical treatment. In addition, a novel cysteine-rich secretory protein (CRBGP) has been isolated and purified from the buccal gland of the lampreys (Lampetra japonica), and it could inhibit the Na+ current of the hippocampus and dorsal root neurons for the first time. In the present study, the progress of the sodium channelopathies and the biological functions of voltage-gated sodium channel blockers are analyzed and summarized.

  4. Drug‐induced Raynaud's phenomenon: beyond β‐adrenoceptor blockers

    Science.gov (United States)

    Khouri, Charles; Blaise, Sophie; Carpentier, Patrick; Villier, Céline; Cracowski, Jean‐Luc

    2016-01-01

    Aim Drug‐induced Raynaud's phenomenon (RP) has long been associated with the use of different drugs, including cancer chemotherapy or β‐adrenoceptor blockers. However, sources report extremely variable prevalence and the level of evidence for each class is heterogeneous. Moreover, new signals are emerging from case reports and small series. Our objective was therefore to review available evidence about this adverse drug effect and to propose a mechanistic approach of drug‐induced RP. Methods A systematic review of English and French language articles was performed through Medline (1946–2015) and Embase (1974–2015). Further relevant papers were identified from the reference lists of retrieved articles. Results We identified 12 classes of drugs responsible for RP, with a variety of underlying mechanisms such as increased sympathetic activation, endothelial dysfunction, neurotoxicity or decreased red blood cell deformability. Cisplatin and bleomycin were associated with the highest risk, followed by β‐adrenoceptor blockers. Recent data suggest a possible involvement of tyrosine kinase inhibitors (TKI), through an unknown mechanism. Conclusion Drug‐induced RP is a probably underestimated adverse drug event, with limited available evidence regarding its prevalence. Although rare, serious complications like critical digital ischaemia have been reported. When these treatments are started in patients with a history of RP, careful monitoring must be made and, if possible, alternative therapies that do not alter peripheral blood flow should be considered. PMID:26949933

  5. [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.

  6. Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration-B mutant of Drosophila.

    Science.gov (United States)

    Sahly, I; Bar Nachum, S; Suss-Toby, E; Rom, A; Peretz, A; Kleiman, J; Byk, T; Selinger, Z; Minke, B

    1992-01-01

    Light accelerates degeneration of photoreceptor cells of the retinal degeneration B (rdgB) mutant of Drosophila. During early stages of degeneration, light stimuli evoke spikes from photoreceptors of the mutant fly; no spikes can be recorded from photoreceptors of the wild-type fly. Production of spike potentials from mutant photoreceptors was blocked by diltiazem, verapamil hydrochloride, and cadmium. Little, if any, effect of the (-)-cis isomer or (+)-cis isomer of diltiazem on the light response was seen. Further, the (+)-cis isomer was approximately 50 times more effective than the (-)-cis isomer in blocking the Ca2+ spikes, indicating that diltiazem action on the rdgB eye is mediated by means of blocking voltage-sensitive Ca2+ channels, rather than by blocking the light-sensitive channels. Application of the Ca(2+)-channel blockers (+)-cis-diltiazem and verapamil hydrochloride to the eyes of rdgB flies over a 7-day period largely inhibited light-dependent degeneration of the photoreceptor cells. Pulse labeling with [32P]phosphate showed much greater incorporation into eye proteins of [32P]phosphate in rdgB flies than in wild-type flies. Retarding the light-induced photoreceptor degeneration in the mutant by Ca(2+)-channel blockers, thus, suggests that toxic increase in intracellular Ca2+ by means of voltage-gated Ca2+ channels, possibly secondary to excessive phosphorylation, leads to photoreceptor degeneration in the rdgB mutant. Images PMID:1309615

  7. Use of Calcium Channel Blockers is Associated with Mortality in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Dominik G. Haider

    2015-12-01

    Full Text Available Background/Aims: The use of antihypertensive medicines has been shown to reduce proteinuria, morbidity, and mortality in patients with chronic kidney disease (CKD. A specific recommendation for a class of antihypertensive drugs is not available in this population, despite the pharmacodynamic differences. We have therefore analysed the association between antihypertensive medicines and survival of patients with chronic kidney disease. Methods: Out of 2687 consecutive patients undergoing kidney biopsy a cohort of 606 subjects with retrievable medical therapy was included into the analysis. Kidney function was assessed by glomerular filtration rate (GFR estimation at the time point of kidney biopsy. Main outcome variable was death. Results: Overall 114 (18.7% patients died. In univariate regression analysis the use of alpha-blockers and calcium channel antagonists, progression of disease, diabetes mellitus (DM type 1 and 2, arterial hypertension, coronary heart disease, peripheral vascular disease, male sex and age were associated with mortality (all pConclusion: The use of calcium channel blockers but not of other antihypertensive medicines is associated with mortality in primarily GN patients with CKD.

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

    Science.gov (United States)

    Anis, Rafik R

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Emil Zeynalov

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

  10. Treatment with oral beta-blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction

    DEFF Research Database (Denmark)

    Ersbøll, A S; Hedegaard, M; Søndergaard, L

    2014-01-01

    OBJECTIVE: To investigate the effect on fetal growth of treatment with oral beta-blockers during pregnancy in women with congenital or acquired heart disease. DESIGN: Historical matched cohort study. SETTING: Centre for Pregnant Women with Heart Disease, Copenhagen University Hospital, Denmark....... POPULATION: A cohort of 175 women with heart disease, grouped according to beta-blocker treatment, and a cohort of 627 women from the overall population matched on seven birthweight-determining factors. METHODS: Differences between groups were tested by simple descriptive statistics and assessed using......-blocker treatment was the only independent predictor of SGA, adjusting for several factors influencing fetal growth (the relative difference in expected birthweight was -12.2%; 95% CI -19.9 to -3.9%; P = 0.001). CONCLUSIONS: In a historical cohort of pregnancies complicated by maternal heart disease, treatment...

  11. Model tests of a once-through steam generator for land-blocker assessment and THEDA code verification. Final report

    International Nuclear Information System (INIS)

    Carter, H.R.; Childerson, M.T.; Moskal, T.E.

    1983-06-01

    The Babcock and Wilcox Company (B and W) operating Once-Through Steam Generators (OTSGs) have experienced leaking tubes in a region adjacent to the untubed inspection lane. The tube leaks have been attributed to an environmentally-assisted fatigue mechanism with moisture transported up the inspection lane being a major factor in the tube-failure process. B and W has developed a hardware modification (lane blockers) to mitigate the detrimental effects of inspection lane moisture. A 30-tube Laboratory Once-through Steam Generator (Designated OTSGC) was designed, fabricated, and tested. Tests were performed with and without five flat-plate lane blockers installed on tube-support plates (TSPs) 10, 11, 12, 13, and 14. The test results were utilized to determine the effectiveness of lane blockers for eliminating moisture transport to the upper tubesheet in the inspection lanes and to benchmark the predictive capabilities of a three-dimensional steam-generator computer code, THEDA

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

    DEFF Research Database (Denmark)

    Abdulla, Jawdat; Køber, Lars; Christensen, Erik

    2005-01-01

    Association (NYHA) classification and exercise tolerance in chronic heart failure. METHODS AND RESULTS: We selected 28 RCTs evaluating beta-blocker versus placebo in addition to ACE inhibitor therapy. Combined results of 23 RCTs showed that beta-blockers improved NYHA class by at least one class with odds...... ratio (OR) 1.80 (1.33-2.43) poxygen uptake and 9 RCTs evaluating 6-min walk distance showed that beta-blockers had no significant effect...... compared with placebo, p=0.484, and p=0.730, respectively. Combined results of the 23 RCTs showed significant reducing effect on all cause mortality with OR=0.69 (0.59-0.82) ptherapy improves dyspnoea and prolongs exercise...

  13. T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers.

    Directory of Open Access Journals (Sweden)

    Wai-Ping Fung-Leung

    Full Text Available Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers.

  14. Beta-blockers and health-related quality of life in patients with peripheral arterial disease and COPD

    Directory of Open Access Journals (Sweden)

    Yvette RBM van Gestel

    2009-05-01

    Full Text Available Yvette RBM van Gestel1, Sanne E Hoeks1, Don D Sin2, Henk Stam3, Frans W Mertens3, Jeroen J Bax4, Ron T van Domburg5, Don Poldermans61Department of Anesthesiology, Erasmus Medical Center, Rotterdam, The Netherlands; 2Department of Medicine, University of British Columbia and The James Hogg iCAPTURe Center, St. Paul’s Hospital, Vancouver, Canada; 3Department of Pulmonology, Erasmus Medical Center, Rotterdam, The Netherlands; 4Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; 5Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands; 6Department of Vascular Surgery, Erasmus Medical Center, Rotterdam, The NetherlandsBackground: Beta-blockers are frequently withheld in patients with cardiovascular disease who also have chronic obstructive pulmonary disease (COPD because of concerns that they might provoke bronchospasm and cause deterioration in health status. Although beta1-selective beta-blockers are associated with reduced mortality in COPD patients, their effects on health status are unknown. The aim of this study was to investigate the relationship between beta-blockers and health-related quality of life (HRQOL in patients with peripheral arterial disease and COPD.Methods: Of the original cohort of 3371 vascular surgery patients, 1310 had COPD of whom 469 survived during long-term follow-up. These COPD patients were sent the Short Form-36 (SF-36 health-related quality of life questionnaire, which was completed and returned by 326 (70% patients.Results: No significant differences in any of the SF-36 domains were observed between COPD patients who did and did not use beta-blockers (p > 0.05 for all. Furthermore, beta-blockers were not associated with any impairment in HRQOL among patients with COPD.Conclusion: Beta-blockers had no material impact on the HRQOL of patients with peripheral arterial disease who also had COPD. This suggests that beta-blockers can, in most circumstances, be

  15. Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia

    DEFF Research Database (Denmark)

    Zakrzewska, Joanna M; Palmer, Joanne; Morisset, Valerie

    2017-01-01

    , can be administered at therapeutic doses without titration, and has shown good tolerability in healthy individuals in phase 1 studies. We therefore assessed the safety and efficacy of BIIB074 in patients with trigeminal neuralgia in a phase 2a study. METHODS: We did a double-blind, multicentre......BACKGROUND: Current standard of care for trigeminal neuralgia is treatment with the sodium channel blockers carbamazepine and oxcarbazepine, which although effective are associated with poor tolerability and the need for titration. BIIB074, a Nav1.7-selective, state-dependent sodium-channel blocker...

  16. Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic.

    Science.gov (United States)

    Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

    2018-01-01

    Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p  = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p  > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p  > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

  17. Adverse respiratory effect of acute β-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Morales, Daniel R; Jackson, Cathy; Lipworth, Brian J; Donnan, Peter T; Guthrie, Bruce

    2014-04-01

    β-Blockers are avoided in asthma over concerns regarding acute bronchoconstriction. Risk is greatest following acute exposure, including the potential for antagonism of β2-agonist rescue therapy. A systematic review of databases was performed to identify all randomized, blinded, placebo-controlled clinical trials evaluating acute β-blocker exposure in asthma. Effect estimates for changes in respiratory function, symptoms, and β2-agonist response were pooled using random effects meta-analysis with heterogeneity investigated. Acute selective β-blockers in the doses given caused a mean change in FEV1 of −6.9% (95% CI, −8.5 to −5.2), a fall in FEV1 of ≥20% in one in eight patients (P=.03), symptoms affecting one in 33 patients (P=.18), and attenuation of concomitant β2-agonist response of −10.2% (95% CI, −14.0 to −6.4). Corresponding values for acute nonselective β-blockers in the doses given were −10.2% (95% CI, −14.7 to −5.6), one in nine patients (P=.02), one in 13 patients (P=.14), and −20.0% (95% CI, −29.4 to −10.7). Following investigation of heterogeneity, clear differences were found for celiprolol and labetalol. A dose-response relationship was demonstrated for selective β-blockers. Selective β-blockers are better tolerated but not completely risk-free. Risk from acute exposure may be mitigated using the smallest dose possible and β-blockers with greater β1-selectivity. β-Blocker-induced bronchospasm responded partially to β2-agonists in the doses given with response blunted more by nonselective β-blockers than selective β-blockers. Use of β-blockers in asthma could possibly be based upon a risk assessment on an individual patient basis.

  18. TO STUDY OF ANTI-INFLAMMATORY EFFECT OF CALCIUM CHANNEL BLOCKERS IN RAT PAW EDEMA MODEL

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2016-02-01

    Full Text Available INTRODUCTION The process of inflammation is one of the most fundamental responses of the vascularised living tissue to local injury.1 Inflammation is a universal host defense process involving a complex network of cell-cell, cell-mediator & tissue interactions.2 AIM AND OBJECTIVES To study of anti-inflammatory effect of calcium channel blockers in rat paw edema model. MATERIALS AND METHODS To evaluate the anti-inflammatory effect with different doses of calcium channel blockers nifedipine, verapamil and standard drug ibuprofen in experimentally induced acute model of inflammation in male Wister rat. Inter drug comparison of anti-inflammatory efficacy of nifedipine, verapamil with standard drug ibuprofen in rats. Divide the animals into 3 groups each comprising at least six rats. Control group inject saline, standard group inject ibuprofen 20 mg/kg. test group inject (nifedipine & verapamil subcutaneously. After 30 min inject 0.1ml 1% (w/v Carrageenin in the plantar region of the left paw of all rats. The left hind paw was measured plethysmograph, immediately (zero hour and 4 hours after the sub plantar injection of Carrageenin. The difference between zero hour volume and the paw volume recorded at the end of 4 hrs. Indicated the actual volume. RESULT The statistical test ANOVA is applied to inter drug comparison. It is found that drug. Nifedipine 1mg/kg (86% has more efficacy significantly as compared to standard drug Ibuprofen 20mg/kg (55%, and drug Verapamil 1mg/kg (71% for its anti-inflammatory action. (F value is 94.27 >tab F 5.82 so this method is statistically highly significant. CONCLUSION Thus it was found that nifedipine has better anti-inflammatory efficacy as compared to ibuprofen, verapamil in various experimental anti-inflammatory models. The various experimental anti-inflammatory models were rat paw edema method. The calcium channel blockers included were nifedipine, verapamil and standard drug ibuprofen. Nifedipine has anti

  19. Relationship between heart failure, concurrent chronic obstructive pulmonary disease and beta-blocker use

    DEFF Research Database (Denmark)

    Sessa, Maurizio; Mascolo, Annamaria; Mortensen, Rikke Nørmark

    2018-01-01

    Aims: To compare the hazard of all-cause, chronic obstructive pulmonary disease (COPD) and heart failure (HF) hospitalization in carvedilol vs. metoprolol/bisoprolol/nebivolol users with COPD and concurrent HF from 2009 to 2012, and to evaluate the use and persistence in treatment of these β......-blockers, their impact on the risk of COPD-related hospitalization, and the factors important for their selection. Methods and results: Cox and logistic regression were used for both unadjusted and adjusted analyses. Carvedilol users had a higher hazard of being hospitalized for HF compared with metoprolol...... persistence time than metoprolol/bisoprolol/nebivolol users. Patients exposed to carvedilol had an odds ratio (OR) of 1.38 (95% CI 1.23-1.56) for being hospitalized due to COPD within 60days after redeeming the first carvedilol prescription, which was similar to that observed in metoprolol...

  20. Beta-blocker subtype and risks of perioperative adverse events following non-cardiac surgery

    DEFF Research Database (Denmark)

    Jørgensen, Mads E.; Sanders, Robert D.; Køber, Lars

    2017-01-01

    performed a Danish Nationwide cohort study, 2005-2011, of patients treated chronically with beta blocker (atenolol, bisoprolol, carvedilol, metoprolol, propranolol, or other) prior to non-cardiac surgery. Risks of 30-day all-cause mortality (ACM) and 30-day major adverse cardiovascular events (MACE) were...... estimated using adjusted logistic regression models and odds ratios with 95% confidence intervals. We identified 61 660 patients, most frequently treated with metoprolol (67% of patients, mean age 69 years, 49% males), atenolol (10% of patients, mean age 68 years, 36% males), or carvedilol (9% of patients......, mean age 68 years, 60% males). The crude incidences of ACM and MACE were 4.1 and 3.5% in patients with metoprolol, 3.0 and 2.3% with atenolol, and 4.8 and 4.6% with carvedilol. In adjusted models, risks were not significantly different with atenolol (ACM; 1.10 [0.92-1.32], MACE; 1.08 [0...

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

    Science.gov (United States)

    Doyle, Jefferson J; Doyle, Alexander J; Wilson, Nicole K; Habashi, Jennifer P; Bedja, Djahida; Whitworth, Ryan E; Lindsay, Mark E; Schoenhoff, Florian; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Ehsan, Hamid; Huso, David; Thomas, Craig J; Caulfield, Mark J; Van Eyk, Jennifer E; Judge, Daniel P; Dietz, Harry C

    2015-10-27

    Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.

  2. The medieval physician Avicenna used an herbal calcium channel blocker, Taxus baccata L.

    Science.gov (United States)

    Tekol, Yalcin

    2007-07-01

    Calcium channel blockers are drugs which are important for current medical therapy. The first examples of synthetic congeners of this class of drugs appear around at the beginning of the 1960s. Review of the current and historical literature shows that Avicenna (Ibn Sina) (980-1037) had used the herbal drug 'Zarnab' (Taxus baccata L.) as a cardiac remedy. The leaves of T. baccata contain an alkaloid mixture (taxines). It was recently demonstrated that this drug possessed calcium channel blocking activity. So, it is evident that Avicenna used a drug with calcium channel blocking activity much earlier than the arrival of synthetic drugs belonging to the same pharmacological group. Copyright 2007 John Wiley & Sons, Ltd.

  3. Turbo Charge CPU Utilization in Fork/Join Using the ManagedBlocker

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    Fork/Join is a framework for parallelizing calculations using recursive decomposition, also called divide and conquer. These algorithms occasionally end up duplicating work, especially at the beginning of the run. We can reduce wasted CPU cycles by implementing a reserved caching scheme. Before a task starts its calculation, it tries to reserve an entry in the shared map. If it is successful, it immediately begins. If not, it blocks until the other thread has finished its calculation. Unfortunately this might result in a significant number of blocked threads, decreasing CPU utilization. In this talk we will demonstrate this issue and offer a solution in the form of the ManagedBlocker. Combined with the Fork/Join, it can keep parallelism at the desired level.

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

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Schou, Morten; Videbaek, Lars

    2007-01-01

    BACKGROUND: Beta-blockers (BBs) are a cornerstone in the treatment of chronic heart failure (HF), but several surveys have documented that many patients are not offered treatment or are not titrated to target doses. In part to address this problem, specialized, nurse-led HF clinics have been...... initiated in many countries. However, little information is available to describe if such programs are successful in initiating and up-titrating BBs in daily clinical practice. AIMS: To assess the proportion of patients with HF due to left ventricular systolic dysfunction on BB treatment three months after...... months (Ptitration continues to be a challenge even in specialized clinics dedicated to this task. Elderly patients appear to be less likely to receive treatment....

  5. Molecular Mechanism of Action and Selectivity of Sodium Ch annel Blocker Insecticides.

    Science.gov (United States)

    Silver, Kristopher; Dong, Ke; Zhorov, Boris S

    2017-01-01

    Sodium channel blocker insecticides (SCBIs) are a relatively new class of insecticides that are represented by two commercially registered compounds, indoxacarb and metaflumizone. SCBIs, like pyrethroids and DDT, target voltage-gated sodium channels (VGSCs) to intoxicate insects. In contrast to pyrethroids, however, SCBIs inhibit VGSCs at a distinct receptor site that overlaps those of therapeutic inhibitors of sodium channels, such as local anesthetics, anticonvulsants and antiarrhythmics. This review will recount the development of the SCBI insecticide class from its roots as chitin synthesis inhibitors, discuss the symptoms of poisoning and evidence supporting inhibition of VGSCs as their mechanism of action, describe the current model for SCBI-induced inhibition of VGSCs, present a model for the receptor for SCBIs on VGSCs, and highlight differences between data collected from mammalian and insect experimental models. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

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

    2014-01-01

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

  7. Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Abildstrom, Steen Z; Rasmussen, Jeppe N

    2005-01-01

    OBJECTIVES: To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. DESIGN: Information about patients with first AMI aged > or = 30 years and the dispensing of beta-blockers and ACE inhibitors from...

  8. 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

  9. Utility of atropine in patients under beta-blocker effect during exercise stress echocardiography

    International Nuclear Information System (INIS)

    Munera, Ana G; Restrepo, Gustavo; Aristizabal, Dagnovar; Cubides, Carlos A

    2006-01-01

    The objective is to assess the usefulness of adding atropine 0.5 to 1.0 mg by intravenous injection during peak exercise in patients under beta-blocker effect that are subjected to exercise stress echocardiography. Population: exercise stress echocardiography was performed in 73 patients receiving beta-blocking agents with basal heart rate below 60 beats per minute (BPM). Two groups were established at random: group I (18 patients that did not receive atropine during maximal exercise) and group II (50 patients from whom 28 received 0.5 mg atropine IV 30 seconds to one minute before concluding the exercise and 22 patients who received 1.0 mg atropine IV 30 seconds to one minute before its conclusion). From a demographic point of view, there were no differences between the two groups. Mean age was 59 ± 10.8 years (57% male). Most of the patients received metoprolol (87%) and no significant statistical differences in relation with the doses were found in these two groups. At the end of the exercise, the patients had a mean heart rate of 84% from their maximal heart rate (MHR). The values post-exercise were 76% at 30 seconds, 68% at 60 sec., 62% at 90 sec., and 59% of the maximal heart rate at 120 sec. When comparing the percentage of the maximal heart rate achieved in maximal exercise and the one observed during the first 120 sec. after exercise, no statistically significant difference was observed between the two groups (p > 0.05). Conclusion: during the performance of stress exercise echocardiography, the administration of intravenous atropine was of no use for incrementing the peak heart rate post-exercise in patients with significant beta-blocker effect (basal heart rate < 60 BPM)

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

    Directory of Open Access Journals (Sweden)

    S Ramakrishnan

    2017-01-01

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

  11. Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers

    Science.gov (United States)

    Aggarwal, Bharat B; Gupta, Subash C; Sung, Bokyung

    2013-01-01

    TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8 PMID:23425071

  12. 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.

  13. Nebivolol, a β1-adrenergic blocker, protects from peritoneal membrane damage induced during peritoneal dialysis.

    Science.gov (United States)

    Liappas, Georgios; González-Mateo, Guadalupe; Aguirre, Anna Rita; Abensur, Hugo; Albar-Vizcaino, Patricia; Parra, Emilio González; Sandoval, Pilar; Ramírez, Laura García; Del Peso, Gloria; Acedo, Juan Manuel; Bajo, María A; Selgas, Rafael; Sánchez Tomero, José A; López-Cabrera, Manuel; Aguilera, Abelardo

    2016-05-24

    Peritoneal dialysis (PD) is a form of renal replacement treatment, which employs the peritoneal membrane (PM) to eliminate toxins that cannot be removed by the kidney. The procedure itself, however, contributes to the loss of the PM ultrafiltration capacity (UFC), leading consequently to the technique malfunction. β-blockers have been considered deleterious for PM due to their association with loss of UFC and induction of fibrosis. Herein we analyzed the effects of Nebivolol, a new generation of β1-blocker, on PM alterations induced by PD fluids (PDF).In vitro: We found that mesothelial cells (MCs) express β1-adrenergic receptor. MCs were treated with TGF-β to induce mesothelial-to-mesenchymal transition (MMT) and co-treated with Nebivolol. Nebivolol reversed the TGF-β effects, decreasing extracellular matrix synthesis, and improved the fibrinolytic capacity, decreasing plasminogen activator inhibitor-1 (PAI-1) and increasing tissue-type plasminogen activator (tPA) supernatant levels. Moreover, Nebivolol partially inhibited MMT and decreased vascular endothelial growth factor (VEGF) and IL-6 levels in supernatants.In vivo: Twenty-one C57BL/6 mice were divided into 3 groups. Control group carried a catheter without PDF infusion. Study group received intraperitoneally PDF and oral Nebivolol during 30 days. PDF group received PDF alone. Nebivolol maintained the UFC and reduced PM thickness, MMT and angiogenesis promoted by PDF. It also improved the fibrinolytic capacity in PD effluents decreasing PAI-1 and IL-8 and increased tPA levels. Nebivolol protects PM from PDF-induced damage, promoting anti-fibrotic, anti-angiogenic, anti-inflammatory and pro-fibrinolytic effects.

  14. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    Directory of Open Access Journals (Sweden)

    J. Lozano-Cuenca

    Full Text Available Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10–9–10–5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10–7.5–10–5 M. The present outcome was not modified by 10–6 M atropine (an antagonist of muscarinic acetylcholine receptors, 3.1×10–7 M glibenclamide (an ATP-sensitive K+ channel blocker, 10–3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker, 10–5 M indomethacin (a prostaglandin synthesis inhibitor, 10–5 M clotrimazole (a cytochrome P450 inhibitor or 10–5 M cycloheximide (a general protein synthesis inhibitor. Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05 by 10–5 M L-NAME (a direct inhibitor of nitric oxide synthase, 10–7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase, 10–6 M KT 5823 (an inhibitor of protein kinase G, 10–2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker and 10–7 M apamin plus 10–7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively, and was blocked by 8×10–2 M potassium (a high concentration and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  15. Life-cycle exposure of fathead minnows to environmentally relevant concentrations of the β-blocker drug propranolol.

    Science.gov (United States)

    Parrott, Joanne L; Balakrishnan, Vimal K

    2017-06-01

    Propranolol is a human pharmaceutical β-blocker that has been detected in municipal wastewater effluents at ng/L to low μg/L. To assess the potential of this compound to affect fish, fathead minnow (Pimephales promelas) were exposed for a life cycle in a flow-through system to nominal propranolol concentrations of 0.87 ng/L, 8.7 ng/L, 87 ng/L, 870 ng/L, and 8700 ng/L. Measured propranolol concentrations were below detection for the 2 lowest exposure concentrations, and were 76 ng/L, 580 ng/L, and 7800 ng/L for the 3 highest exposure concentrations. During the 162-d to 165-d exposure, no significant changes in weights or lengths were seen in fathead minnows, although the highest concentration of propranolol did cause a 15% decrease in survival of larval and juvenile stage fish compared with controls. At maturity, there were no significant changes in condition factor, liver-somatic index, or secondary sex characteristics in propranolol-exposed male or female fish. Female gonadosomatic index was significantly decreased in fish exposed to the highest concentrations of propranolol, probably because of increased egg-laying. Fathead minnows from all propranolol exposures produced more eggs than control fish, with fish exposed to 7800 ng/L propranolol producing 70% more eggs per female (p = 0.060), and having significantly increased clutch size (p = 0.008). Egg quality, % fertilization, % hatching, and % deformities in F1 fry were unaffected by propranolol exposure of fish. Propranolol exposure caused no effects in fathead minnows, except at the highest exposure concentration (7800 ng/L), where there were slight decreases in survival of juvenile minnows, and indications of increased reproduction. The present study is important because it is the first to assess the potential for effects in fish exposed to propranolol for a life cycle. Environ Toxicol Chem 2017;36:1644-1651. © 2016 SETAC. © 2016 SETAC.

  16. 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 pr...

  17. Early Intravenous Beta-Blockers in Patients With ST-Segment Elevation Myocardial Infarction Before Primary Percutaneous Coronary Intervention

    NARCIS (Netherlands)

    Roolvink, Vincent; Ibáñez, Borja; Ottervanger, Jan Paul; Pizarro, Gonzalo; van Royen, Niels; Mateos, Alonso; Dambrink, Jan-Henk E.; Escalera, Noemi; Lipsic, Erik; Albarran, Agustín; Fernández-Ortiz, Antonio; Fernández-Avilés, Francisco; Goicolea, Javier; Botas, Javier; Remkes, Wouter; Hernandez-Jaras, Victoria; Kedhi, Elvin; Zamorano, José L.; Navarro, Felipe; Alfonso, Fernando; García-Lledó, Alberto; Alonso, Joaquin; van Leeuwen, Maarten; Nijveldt, Robin; Postma, Sonja; Kolkman, Evelien; Gosselink, Marcel; de Smet, Bart; Rasoul, Saman; Piek, Jan J.; Fuster, Valentin; van 't Hof, Arnoud W. J.

    2016-01-01

    The impact of intravenous (IV) beta-blockers before primary percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes is not well established. This study sought to conduct the first double-blind, placebo-controlled international multicenter study testing the effect of early IV

  18. Early Intravenous Beta-Blockers in Patients With ST-Segment Elevation Myocardial Infarction Before Primary Percutaneous Coronary Intervention

    NARCIS (Netherlands)

    Roolvink, Vincent; Ibanez, Borja; Ottervanger, Jan Paul; Pizarro, Gonzalo; van Royen, Niels; Mateos, Alonso; Dambrink, Jan-Henk E.; Escalera, Noemi; Lipsic, Erik; Albarran, Agustin; Fernandez-Ortiz, Antonio; Fernandez-Aviles, Francisco; Goicolea, Javier; Botas, Javier; Remkes, Wouter; Hernandez-Jaras, Victoria; Kedhi, Elvin; Zamorano, Jose L.; Navarro, Felipe; Alfonso, Fernando; Garcia-Lledo, Alberto; Alonso, Joaquin; van Leeuwen, Maarten; Nijveldt, Robin; Postma, Sonja; Kolkman, Evelien; Gosselink, Marcel; de Smet, Bart; Rasoul, Saman; Piek, Jan J.; Fuster, Valentin; Van 't Hof, Arnoud W. J.

    2016-01-01

    BACKGROUND The impact of intravenous (IV) beta-blockers before primary percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes is not well established. OBJECTIVES This study sought to conduct the first double-blind, placebo-controlled international multicenter study testing

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    1998-09-01

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

  1. [Clinical cfficacy of calcium channel blockers slow the third generation of lercanidipine in the treatment of patients with arterial hypertension].

    Science.gov (United States)

    Maksimov, M L; Malykhina, A I

    2013-01-01

    The review describes the classification, mechanisms of action, the effects of calcium channel blockers slow and the clinical benefits of dihydropyridine calcium antagonists, the third generation. Presented modern aspects of clinical pharmacology and research results on the efficacy, safety and organoprotective lercanidipine.

  2. Development of selective blockers for Ca2+-activated Cl- channel using Xenopus laevis oocytes with an improved drug screening strategy

    Directory of Open Access Journals (Sweden)

    Oh Soo-Jin

    2008-10-01

    Full Text Available Abstract Background Ca2+-activated Cl- channels (CaCCs participate in many important physiological processes. However, the lack of effective and selective blockers has hindered the study of these channels, mostly due to the lack of good assay system. Here, we have developed a reliable drug screening method for better blockers of CaCCs, using the endogeneous CaCCs in Xenopus laevis oocytes and two-electrode voltage-clamp (TEVC technique. Results Oocytes were prepared with a treatment of Ca2+ ionophore, which was followed by a treatment of thapsigargin which depletes Ca2+ stores to eliminate any contribution of Ca2+ release. TEVC was performed with micropipette containing chelerythrine to prevent PKC dependent run-up or run-down. Under these conditions, Ca2+-activated Cl- currents induced by bath application of Ca2+ to oocytes showed stable peak amplitude when repetitively activated, allowing us to test several concentrations of a test compound from one oocyte. Inhibitory activities of commercially available blockers and synthesized anthranilic acid derivatives were tested using this method. As a result, newly synthesized N-(4-trifluoromethylphenylanthranilic acid with trifluoromethyl group (-CF3 at para position on the benzene ring showed the lowest IC50. Conclusion Our results provide an optimal drug screening strategy suitable for high throughput screening, and propose N-(4-trifluoromethylphenylanthranilic acid as an improved CaCC blocker.

  3. L-type Ca2+ channel blockers promote Ca2+ accumulation when dopamine receptors are activated in striatal neurons.

    Science.gov (United States)

    Eaton, Molly E; Macías, Wendy; Youngs, Rachael M; Rajadhyaksha, Anjali; Dudman, Joshua T; Konradi, Christine

    2004-11-24

    Dopamine (DA) receptor-mediated signal transduction and gene expression play a central role in many brain disorders from schizophrenia to Parkinson's disease to addiction. While trying to evaluate the role of L-type Ca2+ channels in dopamine D1 receptor-mediated phosphorylation of the transcription factor cyclic AMP response element-binding protein (CREB), we found that activation of dopamine D1 receptors alters the properties of L-type Ca2+ channel inhibitors and turns them into facilitators of Ca2+ influx. In D1 receptor-stimulated neurons, L-type Ca2+ channel blockers promote cytosolic Ca2+ accumulation. This leads to the activation of a molecular signal transduction pathway and CREB phosphorylation. In the absence of dopamine receptor stimulation, L-type Ca2+ channel blockers inhibit CREB phosphorylation. The effect of dopamine on L-type Ca2+ channel blockers is dependent on protein kinase A (PKA), suggesting that protein phosphorylation plays a role in this phenomenon. Because of the adverse effect of activated dopamine receptors on L-type Ca2+ channel blocker action, the role of L-type Ca2+ channels in the dopamine D1 receptor signal transduction pathway cannot be assessed with pharmacological tools. However, with antisense technology, we demonstrate that L-type Ca2+ channels contribute to D1 receptor-mediated CREB phosphorylation. We conclude that the D1 receptor signal transduction pathway depends on L-type Ca2+ channels to mediate CREB phosphorylation.

  4. 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

  5. Contraction-induced muscle damage in humans following calcium channel blocker administration

    Science.gov (United States)

    Beaton, Louise J; Tarnopolsky, Mark A; Phillips, Stuart M

    2002-01-01

    Following contraction-induced damage of skeletal muscle there is a loss of calcium homeostasis. Attenuating the damage-induced rise in myocellular calcium concentration may reduce proteolytic activation and attenuate other indices of damage; calcium channel blockers have been shown to be effective in this regard. The effect of administration of a calcium channel blocker (CCB), amlodipine, on indices of muscle damage following a unilateral ‘damage protocol’, during which subjects performed 300 maximal isokinetic (0.52 rad s−1) eccentric contractions with the knee extensors was investigated. The design was a randomized, double-blind crossover. On one occasion, prior to the damage protocol, subjects consumed CCB for 7 days prior to and for 7 days following the damage protocol. Biopsies were taken from the vastus lateralis prior to (baseline) and following the damage protocol at 4 h and 24 h post-damage. Isometric peak knee extensor torque was reduced (P < 0.05) immediately post-, 24 h post- and 48 h post-damage protocol compared to pre-exercise values with no effect of treatment. Desmin disruption was attenuated (P < 0.05) with CCB versus placebo at 4 h post-damage. Z-band streaming was significantly (P < 0.05) elevated compared to baseline at both times post-damage, but was lower with CCB at 4 h (P < 0.05). Damage resulted in increased inflammatory cell (macrophage) infiltration into skeletal muscle at both 4 h and 24 h post-damage, with no effect of CCB. Neutrophil number was elevated by the damage protocol, but was higher at 24 h post-damage in the CCB condition (P < 0.05). Creatine kinase (CK) activity was higher (P < 0.05) at 24 h and 48 h following the damage protocol compared to baseline, with no effect of treatment. In conclusion, the reduction in desmin disruption and Z-band streaming indicates that CCB attenuated, or delayed, the contraction-induced damage to sarcomeric proteins. PMID:12411528

  6. The relationship between functional inhibition and binding for K(Ca2 channel blockers.

    Directory of Open Access Journals (Sweden)

    David Charles Hammond Benton

    Full Text Available Small conductance calcium-activated potassium channels (KCa2.1,2.2,2.3 are blocked with high affinity by both peptide toxins (e.g. apamin and small molecule blockers (e.g. UCL 1848. In electrophysiological experiments, apamin shows subtype selectivity with IC50s of ∼100 pM and ∼1 nM for block KCa2.2 and KCa2.3 respectively. In binding studies, however, apamin appears not to discriminate between KCa2.2 and 2.3 and is reported to have a significantly higher (∼20-200-fold affinity (∼5 pM. This discrepancy between binding and block has been suggested to reflect an unusual mode of action of apamin. However, these binding and electrophysiological block experiments have not been conducted in the same ionic conditions, so it is also possible that the discrepancy arises simply because of differences in experimental conditions. We have now examined this latter possibility. Thus, we measured (125I-apamin binding to intact HEK 293 cells expressing KCa2 channels under the same ionic conditions (i.e. normal physiological conditions that we also used for current block measurements. We find that binding and block experiments agree well if the same ionic conditions are used. Further, the binding of apamin and other blockers showed subtype selectivity when measured in normal physiological solutions (e.g.(125I-apamin bound to KCa2.2 with K L 91±40 pM and to KCa2.3 with K L 711±126 pM, while inhibiting KCa2.2 current at IC50 103±2 pM. We also examined KCa2 channel block in Ca(2+ and Mg(2+ free solutions that mimic conditions reported in the literature for binding experiments. Under these (non-physiological conditions the IC50 for apamin block of KCa2.2 was reduced to 20±3 pM. Our results therefore suggest that the apparent discrepancy between blocking and binding reported in the literature can be largely accounted for by the use of non-physiological ionic conditions in binding experiments.

  7. Comparative analysis of mouse skeletal muscle fibre type composition and contractile responses to calcium channel blocker

    Directory of Open Access Journals (Sweden)

    Järvilehto Matti

    2005-02-01

    Full Text Available Abstract Background In this study, we examined the correlation between excitation-contraction coupling characteristics and skeletal muscle fibre type by (1 localizing the distribution of dihydropyridine receptor (DHPR protein and (2 comparing the effect of DHPR blocker on muscles with different fibre type composition, in order to better understand the differences between contractile phenotypes of fibres and to explain the contradictory reports to date on the interaction of dihydropyridines with skeletal muscle isoform of DHPR. Results Histochemical experiments revealed that fluorophore conjugated dihydropyridines stain selectively the membranes of muscle fibres. The staining was most evident in type IIA fibres. The major fibre type in gluteus and femoris, revealed by mATPase staining, was IIA (45.0 and 38.1 %, respectively. In gastrocnemius the content of IIA fibres was 22.7 %. Contraction forces before and after the addition of blocker for the three muscles investigated were: gluteus 0.075 ± 0.017 N vs. 0.052 ± 0.011 N, femoris 0.045 ± 0.005 N vs. 0.033 ± 0.005 N and gastrocnemius 0.089 ± 0.016 N vs. 0.075 ± 0.014 N, respectively. The attenuation of contraction force proportional to the cross-sectional area of the muscle was significantly (P = 0.023 higher in gluteus (28.3 ± 3.5 % and femoris (27.6 ± 3.2 % as compared to gastrocnemius (16.1 ± 2.5 %. However, no significant change in the control measurements was observed ruling out the possibility of fatigue. Conclusion The results indicate that the attenuation of the contraction force was largest in muscles with a high percentage of type IIA fibres. This supports our finding that the abundance of dihydropyridine receptors of IIA fibres outnumbers that in the other fibre types. The present data show that the correlation of density of dihydropyridine receptors can be one of the important factors influencing the overall contractile properties of the muscle and for its part explain the

  8. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study.

    Science.gov (United States)

    Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John J V; Califf, Robert M; Krum, Henry

    2013-12-09

    To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. NAVIGATOR trial. Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. ClinicalTrials.gov NCT00097786.

  9. 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

  10. 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

    . 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 dosages, patients that received high-dose carvedilol (≥50 mg daily) had a lower all-cause mortality risk (HR 0.873, 0.789-0.966) than patients receiving high-dose (≥200 mg daily) metoprolol (reference). High-dose bisoprolol (≥10 mg daily) was associated with a greater risk of death (HR 1.125, 1.......004-1.261). High-dose carvedilol was associated with significantly lower all-cause hospitalization risk (HR 0.842, 0.774-0.915) than high-dose metoprolol (reference), while high-dose bisoprolol had insignificantly lower risk than high-dose metoprolol (HR 0.948, 0.850-1.057). CONCLUSIONS: Heart failure patients...

  11. Effects of Tumor Necrosis Factor Blocker on Salicylate-Induced Tinnitus in Mice.

    Science.gov (United States)

    Hwang, Juen-Haur; Huang, David Chang-Wei; Lu, Yin-Chang; Yang, Wei-Shiung; Liu, Tien-Chen

    2017-06-01

    Neuroinflammation is considered a novel mechanism for acute tinnitus. Here, we investigated the effects of a tumor necrosis factor (TNF) blocker on the gene expression of inflammatory-cytokine in the cochlea in a tinnitus animal model. Enbrel® (30 mg/kg, intraperitoneally (i.p.)) were administrated to the mice with the salicylate induced tinnitus for 3 days. Tinnitus score and mRNA expression levels of TNFR1, TNFR2, and N-methyl-d-aspartate receptor subunit 2B (NR2B) and its downstream regulatory element antagonist modulator (DREAM) in the cochlea of mice were measured and compared to the control. The tinnitus score significantly decreased in the Enbrel® treated group. The mRNA levels of both TNFR1 and TNFR2 were significantly lower in the treatment than in the control group. The mRNA levels of NR2B and DREAM followed a similar trend. we found that treatment with 30 mg/ kg Enbrel® decreased salicylate-induced behavior associated with tinnitus and reduced the mRNA expression levels of TNFR1/R2, NR2B, and DREAM in the cochlea of mice. These findings supported the hypothesis that neuroinflammation might be a novel mechanism for salicylate-induced tinnitus.

  12. 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.

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

    Science.gov (United States)

    Meyer, Matthias R; Barton, Matthias

    2018-02-01

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

  14. 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.

  15. Calcium channel blockers as tocolytics: principles of their actions, adverse effects and therapeutic combinations.

    Science.gov (United States)

    Gáspár, Róbert; Hajagos-Tóth, Judit

    2013-05-23

    Dihydropyridine Ca2+ channel blockers (CCBs) are widely accepted in the treatment of premature labour. Their mechanism of action in tocolysis involves the blockade of L-type Ca2+ channels, influenced by the Ca2+-activated K+ channels, beta-adrenergic receptors (β-ARs) and sexual hormones. In clinical practice, most experience has been gained with the use of nifedipine, whose efficacy is superior or comparable to those of β-agonists and oxytocin antagonists. Additionally, it has a favourable adverse effect profile as compared with the majority of other tocolytics. The most frequent and well-tolerated side-effects of CCBs are tachycardia, headache and hypotension. In tocolytic therapy efforts are currently being made to find combinations of tocolytic agents that yield better therapeutic action. The available human and animal studies suggest that the combination of CCBs with β-AR agonists is beneficial, although such combinations can pose risk of pulmonary oedema in multiple pregnancies and maternal cardiovascular diseases. Preclinical data indicate the potential benefit of combinations of CCBs and oxytocin antagonists. However, the combinations of CCBs with progesterone or cyclooxygenase inhibitors may decrease their efficacy. The CCBs are likely to remain one of the most important groups of drugs for the rapid inhibition of premature uterine contractions. Their significance may be magnified by further clinical studies on their combined use for tocolysis.

  16. Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy.

    Science.gov (United States)

    Dilena, Robertino; Striano, Pasquale; Gennaro, Elena; Bassi, Laura; Olivotto, Sara; Tadini, Laura; Mosca, Fabio; Barbieri, Sergio; Zara, Federico; Fumagalli, Monica

    2017-04-01

    Recent clinical evidence supports a targeted therapeutic approach for genetic epileptic encephalopathies based on the molecular dysfunction. A 2-day-old male infant presented with epileptic encephalopathy characterized by burst-suppression EEG background and tonic-clonic migrating partial seizures. The condition was refractory to phenobarbital, pyridoxine, pyridoxal phosphate and levetiracetam, but a dramatic response to an intravenous loading dose of phenytoin was documented by video-EEG monitoring. Over weeks phenytoin was successfully switched to carbamazepine to prevent seizure relapses associated with difficulty in maintaining proper blood levels of phenytoin. Genetic analysis identified a novel de novo heterozygous mutation (c.[4633A>G]p.[Met1545Val]) in SCN2A. At two years and three months of age the patient is still seizure-free on carbamazepine, although a developmental delay is evident. Sodium channel blockers represent the first-line treatment for confirmed or suspected SCN2A-related epileptic encephalopathies. In severe cases with compatible electro-clinical features we propose a treatment algorithm based on a test trial with high dose intravenous phenytoin followed in case of a positive response by carbamazepine, more suitable for long-term maintenance treatment. Because of their rarity, collaborative studies are needed to delineate shared therapeutic protocols for EIEE based on the electro-clinical features and the presumed underlying genetic substrate. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Pieter Spincemaille

    2014-10-01

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

  18. The potential of Na+/Ca2+ exchange blockers in the treatment of cardiac disease.

    Science.gov (United States)

    Hobai, Ion A; O'Rourke, Brian

    2004-06-01

    The Na(+)/Ca(2+) exchanger (NCX), a surface membrane antiporter, is the primary pathway for Ca(2+) efflux from the cardiac cell and a determinant of both the electrical and contractile state of the heart. Enhanced expression of NCX has recently been recognised as one of the molecular mechanisms that contributes to reduced Ca(2+) release, impaired contractility and an increased risk of arrhythmias during the development of cardiac hypertrophy and failure. The NCX has also been implicated in the mechanism of arrhythmias and cellular injury associated with ischaemia and reperfusion. Hence, NCX blockade represents a potential therapeutic strategy for treating cardiac disease, however, its reversibility and electrogenic properties must be taken into consideration when predicting the outcome. NCX inhibition has been demonstrated to be protective against ischaemic injury and to have a positive inotropic and antiarrhythmic effect in failing heart cells. However, progress has been impaired by the absence of clinically useful agents. Two drugs, KB-R7943 and SEA-0400, have been developed as NCX blockers but both lack specificity. Selective peptide inhibitors have been well characterised but are active only when delivered to the intracellular space. Gene therapy strategies may circumvent the latter problem in the future. This review discusses the effects of NCX blockade, supporting its potential as a new cardiovascular therapeutic strategy.

  19. L-type calcium channel blockers, morphine and pain: Newer insights

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2010-01-01

    Full Text Available Earlier, we had reported that co-administration of opioids and L-type calcium channel blockers (L-CCBs like diltiazem could prove useful in the treatment of cancer pain. Much of this report was based upon earlier published work involving animal models of pain exposed to brief periods of noxious radiant heat without any tissue injury. However, pain in clinical situations usually result from tissue injury. Thus, the aim of the current investigation was to study the analgesic effect of this combination of drugs in the rat formalin test which is associated with actual tissue injury. Wistar rats (n=60 received either L-CCB (nifedipine/nimodipine/verapamil/diltiazem i.p. or morphine (s.c. or both drugs. The formalin test was done 30 min after morphine or placebo injection. The naloxone reversal test was also done. Administration of L-CCBs alone, particularly diltiazem, increased pain in the formalin test. In contrast, co-administration of these L-CCBs with morphine led to decreased pain response, though statistically significant decrease was noted only with nimodipine + morphine. Naloxone reversed this analgesic effect, indicating that it was primarily an opioid-mediated effect. The results show that administration of L-CCBs alone may prove counterproductive in the therapeutic management of pain (anti-analgesic effect. However, co-administration of both drugs (morphine and nimodipine in quick succession could lead to adequate pain relief.

  20. Use of Calcium Channel Blockers and Breast Cancer Risk in the Women's Health Initiative.

    Science.gov (United States)

    Brasky, Theodore M; Krok-Schoen, Jessica L; Liu, Jingmin; Chlebowski, Rowan T; Freudenheim, Jo L; Lavasani, Sayeh; Margolis, Karen L; Qi, Lihong; Reding, Kerryn W; Shields, Peter G; Simon, Michael S; Wactawski-Wende, Jean; Wang, Ange; Womack, Catherine; Manson, JoAnn E

    2017-08-01

    Background: Use of calcium channel blockers (CCBs) has been associated with increased risk of breast cancer in some, but not all, studies. Differences in reported associations from prior studies may be due, in part, to inadequate control of confounding factors. Methods: Participants were 28,561 postmenopausal women from the Women's Health Initiative who reported use of either CCBs or other antihypertensive medications (AHMs) at baseline; 1,402 incident breast cancer cases were diagnosed during 12 years of follow-up. Adjusted Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the associations between CCB use relative to other AHM use and breast cancer risk. Results: Use of CCBs was not associated with breast cancer risk (HR, 1.06; 95% CI, 0.94-1.20) relative to use of other AHMs. Associations approximated the null value when CCBs were considered by duration of use, length of action, or drug class. Conclusions: We provide additional evidence that CCBs do not influence breast cancer risk in postmenopausal women. Impact: The results from this study, which includes strong control for potential confounding factors, cast doubt on increases in risk with CCBs. Cancer Epidemiol Biomarkers Prev; 26(8); 1345-8. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. The effect of the molecular properties of calcium channel blockers on their elimination route

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    Trbojević-Stanković Jasna B.

    2015-01-01

    Full Text Available Calcium channel blockers (CCBs are among the most widely used drugs in cardiovascular medicine. In this study, nine CCBs (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem were investigated to assess the relationship between their molecular properties and elimination data obtained from literature. The descriptors of the molecular properties of CCBs were calculated using three software packages. The relationship between computed molecular properties and elimination data collected from relevant literature, initially investigated with simple linear regression analysis, showed poor correlation (R2 <0.25. Application of molecular weight or volume data as additional independent variable, multiple linear regression (MLR revealed better correlations (R2 ~ 0.38 between CCB renal and fecal elimination data and their lipophilicity. Excluding nimodipine from the calculations resulted in more acceptable correlations. The best correlations were established after computed lipophilicity descriptor and molecular weight were applied (R2 = 0.66 with acceptable probability value. [Projekat Ministarstva nauke Republike Srbije, br. TR34031

  2. Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans.

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    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. 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.

  4. Retinal ganglion cell neuroprotection by an angiotensin II blocker in an ex vivo retinal explant model.

    Science.gov (United States)

    White, Andrew J R; Heller, Janosch P; Leung, Johahn; Tassoni, Alessia; Martin, Keith R

    2015-12-01

    An ex vivo organotypic retinal explant model was developed to examine retinal survival mechanisms relevant to glaucoma mediated by the renin angiotensin system in the rodent eye. Eyes from adult Sprague Dawley rats were enucleated immediately post-mortem and used to make four retinal explants per eye. Explants were treated either with irbesartan (10 µM), vehicle or angiotensin II (2 μM) for four days. Retinal ganglion cell density was estimated by βIII tubulin immunohistochemistry. Live imaging of superoxide formation with dihydroethidium (DHE) was performed. Protein expression was determined by Western blotting, and mRNA expression was determined by RT-PCR. Irbesartan (10 µM) almost doubled ganglion cell survival after four days. Angiotensin II (2 µM) reduced cell survival by 40%. Sholl analysis suggested that irbesartan improved ganglion cell dendritic arborisation compared to control and angiotensin II reduced it. Angiotensin-treated explants showed an intense DHE fluorescence not seen in irbesartan-treated explants. Analysis of protein and mRNA expression determined that the angiotensin II receptor At1R was implicated in modulation of the NADPH-dependent pathway of superoxide generation. Angiotensin II blockers protect retinal ganglion cells in this model and may be worth further investigation as a neuroprotective treatment in models of eye disease. © The Author(s) 2015.

  5. Polyaniline-graphene oxide nanocomposite sensor for quantification of calcium channel blocker levamlodipine.

    Science.gov (United States)

    Jain, Rajeev; Sinha, Ankita; Khan, Ab Lateef

    2016-08-01

    A novel polyaniline-graphene oxide nanocomposite (PANI/GO/GCE) sensor has been fabricated for quantification of a calcium channel blocker drug levamlodipine (LAMP). Fabricated sensor has been characterized by electrochemical impedance spectroscopy, square wave and cyclic voltammetry, Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy. The developed PANI/GO/GCE sensor has excellent analytical performance towards electrocatalytic oxidation as compared to PANI/GCE, GO/GCE and bare GCE. Under optimized experimental conditions, the fabricated sensor exhibits a linear response for LAMP for its oxidation over a concentration range from 1.25μgmL(-1) to 13.25μgmL(-1) with correlation coefficient of 0.9950 (r(2)), detection limit of 1.07ngmL(-1) and quantification limit of 3.57ngmL(-1). The sensor shows an excellent performance for detecting LAMP with reproducibility of 2.78% relative standard deviation (RSD). The proposed method has been successfully applied for LAMP determination in pharmaceutical formulation with a recovery from 99.88% to 101.75%. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Biopharmaceutics classification of selected beta-blockers: solubility and permeability class membership.

    Science.gov (United States)

    Yang, Yongsheng; Faustino, Patrick J; Volpe, Donna A; Ellison, Christopher D; Lyon, Robbe C; Yu, Lawrence X

    2007-01-01

    The purpose of this study was to determine the permeability and solubility of seven beta-blockers (acebutolol, atenolol, labetalol, metoprolol, nadolol, sotalol, and timolol) and to classify them according to the Biopharmaceutics Classification System (BCS). Apparent permeability coefficients (Papp) were measured using the Caco-2 cell line, and the solubility was determined at 37 degrees C over a pH range of 1.0-7.5. The permeability coefficients ranged from 1.0x10(-7) to 4.8x10(-5) cm/s. On the basis of the in vitro permeability and solubility data observed in the study, labetolol, metoprolol, and timolol can be categorized as BCS Class I drugs, whereas acebutolol, atenolol, and nadolol belong to BCS Class III. The permeability coefficients in Caco-2 cells were consistent with the reported extent of intestinal absorption in humans for all drugs except sotalol. Sotalol displayed low permeability in the Caco-2 cell line, but the extent of intestinal absorption in humans is over 90%. The low permeability through the Caco-2 monolayers might be largely related to its low lipophilicity. In addition, the difference between the tightness of the intercellular junction in vivo and in vitro may partially contribute to this disparity in the sotalol permeability of in vivo and in vitro.

  7. The Receptor Site and Mechanism of Action of Sodium Channel Blocker Insecticides.

    Science.gov (United States)

    Zhang, Yongqiang; Du, Yuzhe; Jiang, Dingxin; Behnke, Caitlyn; Nomura, Yoshiko; Zhorov, Boris S; Dong, Ke

    2016-09-16

    Sodium channels are excellent targets of both natural and synthetic insecticides with high insect selectivity. Indoxacarb, its active metabolite DCJW, and metaflumizone (MFZ) belong to a relatively new class of sodium channel blocker insecticides (SCBIs) with a mode of action distinct from all other sodium channel-targeting insecticides, including pyrethroids. Electroneutral SCBIs preferably bind to and trap sodium channels in the inactivated state, a mechanism similar to that of cationic local anesthetics. Previous studies identified several SCBI-sensing residues that face the inner pore of sodium channels. However, the receptor site of SCBIs, their atomic mechanisms, and the cause of selective toxicity of MFZ remain elusive. Here, we have built a homology model of the open-state cockroach sodium channel BgNav1-1a. Our computations predicted that SCBIs bind in the inner pore, interact with a sodium ion at the focus of P1 helices, and extend their aromatic moiety into the III/IV domain interface (fenestration). Using model-driven mutagenesis and electrophysiology, we identified five new SCBI-sensing residues, including insect-specific residues. Our study proposes the first three-dimensional models of channel-bound SCBIs, sheds light on the molecular basis of MFZ selective toxicity, and suggests that a sodium ion located in the inner pore contributes to the receptor site for electroneutral SCBIs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Directory of Open Access Journals (Sweden)

    V. I. Podzolkov

    2017-01-01

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

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

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    Peter Cseplo

    Full Text Available Nebivolol is known to have beta-1 blocker activity, but it was also suggested that it elicits relaxation of the peripheral arteries in part via release of nitric oxide (NO. However, the effect of nebivolol on the vasomotor tone of cerebral arteries is still unclear.To assess the effects of nebivolol on the diameter of isolated rat basilar arteries (BA in control, in the presence of inhibitors of vasomotor signaling pathways of know action and hemolysed blood.Vasomotor responses were measured by videomicroscopy and the intracellular Ca2+ by the Fura-2 AM ratiometric method. Under control conditions, nebivolol elicited a substantial dilation of the BA (from 216±22 to 394±20 μm; p<0.05 in a concentration-dependent manner (10-7 to 10-4 M. The dilatation was significantly reduced by endothelium denudation or by L-NAME (inhibitor of NO synthase or by SQ22536 (adenylyl cyclase blocker. Dilatation of BA was also affected by beta-2 receptor blockade with butoxamine, but not by the guanylate cyclase blocker ODQ. Interestingly, beta-1 blockade by atenolol inhibited nebivolol-induced dilation. Also, the BKCa channel blocker iberiotoxin and KCa channel inhibitor TEA significantly reduced nebivolol-induced dilation. Nebivolol significantly reduced smooth muscle Ca2+ level, which correlated with the increases in diameters and moreover it reversed the hemolysed blood-induced constriction of BA.Nebivolol seems to have an important dilator effect in cerebral arteries, which is mediated via several vasomotor mechanisms, converging on the reduction of smooth muscle Ca2+ levels. As such, nebivolol may be effective to improve cerebral circulation in various diseased conditions, such as hemorrhage.

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

    Czech Academy of Sciences Publication Activity Database

    Kurtz, T. W.; Pravenec, Michal

    2008-01-01

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

  11. Effects of KCNQ1 channel blocker, 293B, on the acetylcholine-induced Cl- secretion of rat pancreatic acini.

    Science.gov (United States)

    Lee, Ji Eun; Park, Hyung Seo; Uhm, Dae-Yong; Kim, Sung Joon

    2004-05-01

    In rat pancreatic acini (RPAs), acetylcholine (ACh) typically induces a tonic depolarization of membrane potential (Vm) via increasing cytoplasmic Ca2+ concentration and subsequent activation of Cl- channels. In this study, to investigate the role of K+ channels during the ACh-induced Cl- secretion, the intracellular Cl- concentration ([Cl-]i) of RPAs was monitored using SPQ, a fluorescent dye quenchable by Cl-, and the effects of K+ channel blockers were examined. Also, the secretion of fluid and enzyme from the whole pancreas of rat was measured. The fluorescence of RPAs loaded with SPQ (FSPQ) was slightly increased by the application of ACh (ACh-Delta FSPQ), indicating net secretion of Cl-. However, the relative change of FSPQ normalized to the control fluorescence (F/F0) of RPAs was only about 20% of the effect observed in rat submandibular gland acinus. The ACh-Delta FSPQ of RPAs was not influenced by the pretreatment with 293B (20 micromol/L), a blocker of KCNQ-type K+ channels. Even the cocktail of K+ channel blockers (10 mmol/L TEA, 3 mmol/L Ba2+, 20 micromol/L 293B) exerted only minute inhibitory effects on ACh-Delta FSPQ in RPAs. In the vascularly perfused rat pancreas, the fluid and enzyme secretion induced by ACh was directly measured. 293B and HMR-1556, both specific blockers of KCNQ1 channel, did not block but even enhanced the secretion of fluid and amylase. These results suggest that the role of KCNQ1 channels may not be essential in the Ca2+-mediated Cl- secretion in rat pancreatic acini.

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

    Science.gov (United States)

    Iwata, S; Nomoto, M; Fukuda, T

    1996-10-01

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

  13. Oral physiology, nutrition and quality of life in diabetic patients associated or not with hypertension and beta-blockers therapy.

    Science.gov (United States)

    Pereira, L J; Foureaux, R C; Pereira, C V; Alves, M C; Campos, C H; Rodrigues Garcia, R C M; Andrade, E F; Gonçalves, T M S V

    2016-07-01

    The relationship between type 2 diabetes oral physiology, nutritional intake and quality of life has not been fully elucidated. We assessed the impact of type 2 diabetes - exclusive or associated with hypertension with beta-blockers treatment - on oral physiology, mastication, nutrition and quality of life. This cross-sectional study was performed with 78 complete dentate subjects (15 natural teeth and six masticatory units minimum; without removable or fixed prostheses), divided into three groups: diabetics (DM) (n = 20; 45·4 ± 9·5 years), diabetics with hypertension and receiving beta-blockers treatment (DMH) (n = 19; 41·1 ± 5·1 years) and controls (n = 39; 44·5 ± 11·7 years) matched for gender, age and socioeconomic status. Blood glucose, masticatory performance, swallowing threshold, taste, food intake, stimulated and unstimulated salivary flow, pH and buffering capacity of saliva were assessed. Glycemia was higher in DM than in controls (P quality of life. Both stimulated and unstimulated salivary flow rate were lower in DMH (P diabetes did not alter oral physiology, nutrition or quality of life. However, when hypertension and beta-blockers treatment were associated with diabetes, the salivary flow rate, chewing cycles and number of teeth decreased. © 2016 John Wiley & Sons Ltd.

  14. Structure-activity relationship study and discovery of indazole 3-carboxamides as calcium-release activated calcium channel blockers.

    Science.gov (United States)

    Bai, Sha; Nagai, Masazumi; Koerner, Steffi K; Veves, Aristidis; Sun, Lijun

    2017-02-01

    Aberrant activation of mast cells contributes to the development of numerous diseases including cancer, autoimmune disorders, as well as diabetes and its complications. The influx of extracellular calcium via the highly calcium selective calcium-release activated calcium (CRAC) channel controls mast cell functions. Intracellular calcium homeostasis in mast cells can be maintained via the modulation of the CRAC channel, representing a critical point for therapeutic interventions. We describe the structure-activity relationship study (SAR) of indazole-3-carboxamides as potent CRAC channel blockers and their ability to stabilize mast cells. Our SAR results show that the unique regiochemistry of the amide linker is critical for the inhibition of calcium influx, the release of the pro-inflammatory mediators β-hexosaminidase and tumor necrosis factor α by activated mast cells. Thus, the indazole-3-carboxamide 12d actively inhibits calcium influx and stabilizes mast cells with sub-μM IC 50 . In contrast, its reverse amide isomer 9c is inactive in the calcium influx assay even at 100μM concentration. This requirement of the specific 3-carboxamide regiochemistry in indazoles is unprecedented in known CRAC channel blockers. The new structural scaffolds described in this report expand the structural diversity of the CRAC channel blockers and may lead to the discovery of novel immune modulators for the treatment of human diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    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...

  16. The effects of nifekalant hydrochloride on the spatial dispersion of repolarization after direct current defibrillation in patients with oral amiodarone and β-blocker therapy

    Directory of Open Access Journals (Sweden)

    Keiko Maeda

    2014-06-01

    Conclusions: NIF suppressed the deterioration of the SDR after ICD shock. This might be one of the mechanisms by which NIF suppresses recurrence of ventricular tachyarrhythmia just after ICD shock in patients with oral amiodarone and β-blocker therapy.

  17. Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Abildstrom, Steen Z; Rasmussen, Jeppe N

    2005-01-01

    -diuretics and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR = 1.86, CI: 1.72-2.01). Women, patients aged or = 80 years and patients not taking loop......-diuretics received ACE inhibitors less frequently, but patients not taking loop-diuretics had the greatest increase. CONCLUSIONS: Beta-blocker use increased markedly post-AMI from 1995 to 2002, whereas ACE inhibitor use increased modestly. The results suggested undertreatment of women, elderly patients and people......OBJECTIVES: To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. DESIGN: Information about patients with first AMI aged > or = 30 years and the dispensing of beta-blockers and ACE inhibitors from...

  18. Effect of beta-blocker therapy on the risk of infections and death after acute stroke--a historical cohort study.

    Directory of Open Access Journals (Sweden)

    Ilko L Maier

    Full Text Available BACKGROUND: Infections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans. METHODS: 625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models. RESULTS: 553 (88.3% patients were admitted with ischemic stroke, the remaining 72 (11.7% had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5-16 points. 301 (48.2% patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77-1.30, p = 0.995. Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43-0.98, p = 0.040. 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65-2.77, p = 0.425, while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20-3.10, p = 0.006. CONCLUSIONS: Beta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.

  19. Efficacy of α-blocker in improving ureteral stent-related symptoms: a meta-analysis of both direct and indirect comparison

    Directory of Open Access Journals (Sweden)

    He F

    2016-05-01

    Full Text Available Feng He, Li-bo Man, Gui-zhong Li, Ning Liu Department of Urinary Surgery, Beijing Jishuitan Hospital, Beijing, People’s Republic of China Objective: To critically evaluate the efficacy of an α-blocker in improving ureteral-stent-related symptoms and preliminarily investigate the difference between different types of α-blockers. Methods: Relevant randomized controlled trials were identified through searching PubMed, the Cochrane Library, Embase, and other sources. After quality assessment and data abstraction, direct comparison based on the Ureteral Stent-related Symptom Questionnaire (USSQ between α-blockers and control was performed by RevMan 5.3. Indirect comparison between different types of α-blockers was performed by ITC 1.0. Sensitive and subgroup analyses were used to handle important clinical factors. Results: Sixteen randomized controlled trials containing 1,489 cases were included. Compared with control, α-blockers significantly reduced the overall urinary symptom, pain index, general health index, and scores related to sexual matters, while no significant difference was found in work performance and additional problem scores. Subgroup analysis showed that the duration of stent insertion, patient’s age, stent size, and the type of α-blocker had the potential to influence the outcomes. Through indirect comparison, we found alfuzosin and terazosin to be better than tamsulosin in pain relief and general health improvement. Conclusion: α-Blocker was effective in treating ureteral stent-related symptoms, as it improved the major indexes of USSQ post-insertion or post-removal. Alfuzosin and terazosin seemed to be better than tamsulosin, which needs further verification because of the lack of direct comparison currently. Keywords: α-blocker, tamsulosin, alfuzosin, terazosin, ureteral stent-related discomfort

  20. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    Directory of Open Access Journals (Sweden)

    Mugoša S

    2016-08-01

    Full Text Available Snežana Mugoša,1,2 Nataša Djordjević,3 Nina Djukanović,4 Dragana Protić,5 Zoran Bukumirić,6 Ivan Radosavljević,7 Aneta Bošković,8 Zoran Todorović5,9 1Department of Pharmacotherapy, Faculty of Pharmacy, University of Montenegro, 2Clinical Trial Department, Agency for Medicines and Medical Devices of Montenegro, Podgorica, Montenegro; 3Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 4High Medical School “Milutin Milanković”, Belgrade, 5Department of Pharmacology, Clinical Pharmacology and Toxicology, 6Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, 7Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; 8Clinic for Heart Diseases, Clinical Centre of Montenegro, Podgorica, Montenegro; 9Department of Clinical Immunology and Allergy, Medical Center “Bežanijska kosa”, Belgrade, Serbia Abstract: The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6 poor metabolizer alleles (*3, *4, *5, and *6 on a Montenegrin population and its impact on developing adverse drug reactions (ADRs of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9% patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001, with ADRs’ occurrence significantly

  1. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial.

    Science.gov (United States)

    Scheer, Frank A J L; Morris, Christopher J; Garcia, Joanna I; Smales, Carolina; Kelly, Erin E; Marks, Jenny; Malhotra, Atul; Shea, Steven A

    2012-10-01

    In the United States alone, approximately 22 million people take beta-blockers chronically. These medications suppress endogenous nighttime melatonin secretion, which may explain a reported side effect of insomnia. Therefore, we tested whether nightly melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers. Randomized, double-blind, placebo-controlled, parallel-group design. Clinical and Translational Research Center at Brigham and Women's Hospital, Boston. Sixteen hypertensive patients (age 45-64 yr; 9 women) treated with the beta-blockers atenolol or metoprolol. Two 4-day in-laboratory admissions including polysomnographically recorded sleep. After the baseline assessment during the first admission, patients were randomized to 2.5 mg melatonin or placebo (nightly for 3 weeks), after which sleep was assessed again during the second 4-day admission. Baseline-adjusted values are reported. One patient was removed from analysis because of an unstable dose of prescription medication. In comparison with placebo, 3 weeks of melatonin supplementation significantly increased total sleep time (+36 min; P = 0.046), increased sleep efficiency (+7.6%; P = 0.046), and decreased sleep onset latency to Stage 2 (-14 min; P = 0.001) as assessed by polysomnography. Compared with placebo, melatonin significantly increased Stage 2 sleep (+41 min; P = 0.037) but did not significantly change the durations of other sleep stages. The sleep onset latency remained significantly shortened on the night after discontinuation of melatonin administration (-25 min; P = 0.001), suggesting a carryover effect. n hypertensive patients treated with beta-blockers, 3 weeks of nightly melatonin supplementation significantly improved sleep quality, without apparent tolerance and without rebound sleep disturbance during withdrawal of melatonin supplementation (in fact, a positive carryover effect was demonstrated). These findings may assist in developing countermeasures

  2. Antagonism of Lidocaine Inhibition by Open-Channel Blockers That Generate Resurgent Na Current

    Science.gov (United States)

    Bant, Jason S.; Aman, Teresa K.; Raman, Indira M.

    2013-01-01

    Na channels that generate resurgent current express an intracellular endogenous open-channel blocking protein, whose rapid binding upon depolarization and unbinding upon repolarization minimizes fast and slow inactivation. Na channels also bind exogenous compounds, such as lidocaine, which functionally stabilize inactivation. Like the endogenous blocking protein, these use-dependent inhibitors bind most effectively at depolarized potentials, raising the question of how lidocaine-like compounds affect neurons with resurgent Na current. We therefore recorded lidocaine inhibition of voltage-clamped, tetrodotoxin-sensitive Na currents in mouse Purkinje neurons, which express a native blocking protein, and in mouse hippocampal CA3 pyramidal neurons with and without a peptide from the cytoplasmic tail of NaVβ4 (the β4 peptide), which mimics endogenous open-channel block. To control channel states during drug exposure, lidocaine was applied with rapid-solution exchange techniques during steps to specific voltages. Inhibition of Na currents by lidocaine was diminished by either the β4 peptide or the native blocking protein. In peptide-free CA3 cells, prolonging channel opening with a site-3 toxin, anemone toxin II, reduced lidocaine inhibition; this effect was largely occluded by open-channel blockers, suggesting that lidocaine binding is favored by inactivation but prevented by open-channel block. In constant 100 μM lidocaine, current-clamped Purkinje cells continued to fire spontaneously. Similarly, the β4 peptide reduced lidocaine-dependent suppression of spiking in CA3 neurons in slices. Thus, the open-channel blocking protein responsible for resurgent current acts as a natural antagonist of lidocaine. Neurons with resurgent current may therefore be less susceptible to use-dependent Na channel inhibitors used as local anesthetic, antiarrhythmic, and anticonvulsant drugs. PMID:23486968

  3. Use of the tumor necrosis factor-blockers for Crohn's disease.

    Science.gov (United States)

    Thomson, Alan B R; Gupta, Milli; Freeman, Hugh J

    2012-09-21

    The use of anti-tumor necrosis factor-α therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn's disease study thirty years ago. The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses. In general, it is suggested that tumor necrosis factor-α blockers (TNFBs) are indicated (1) for persons with moderately-severe Crohn's disease or ulcerative colitis (UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause (8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate; (2) non-responsive perianal disease; and (3) severe UC not responding to a 3-d to 5-d course of steroids. Once TNFBs have been introduced and the patient is responsive, therapy given by the IV and SC rate must be continued. It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy, and when or if TNFB may be weaned and discontinued. The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient's illness needs to be confirmed. The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB, and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic. Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high, the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

  4. The marine algal toxin azaspiracid is an open state blocker of hERG potassium channels

    Science.gov (United States)

    Twiner, Michael J.; Doucette, Gregory J.; Rasky, Andrew; Huang, Xi-Ping; Roth, Bryan L.; Sanguinetti, Michael C.

    2012-01-01

    Azaspiracids (AZA) are polyether marine dinoflagellate toxins that accumulate in shellfish and represent an emerging human health risk. Although human exposure is primarily manifested by severe and protracted diarrhea, this toxin class has been shown to be highly cytotoxic, a teratogen to developing fish, and a possible carcinogen in mice. Until now, AZA's molecular target(s) has not yet been determined. Using three independent methods (voltage clamp, channel binding assay, and thallium flux assay), we have for the first time demonstrated that AZA1, AZA2, and AZA3 each bind to and block the hERG (human ether-à-go-go related gene) potassium channel heterologously expressed in HEK-293 mammalian cells. Inhibition of K+ current for each AZA analogue was concentration-dependent (IC50 value range: 0.64 - 0.84 μM). The mechanism of hERG channel inhibition by AZA1 was investigated further in Xenopus oocytes where it was shown to be an open state-dependent blocker and, using mutant channels, to interact with F656 but not with Y652 within the S6 transmembrane domain that forms the channel's central pore. AZA1, AZA2, and AZA3 were each shown to inhibit [3H]dofetilide binding to the hERG channel and thallium ion flux through the channel (IC50 value range: 2.1 – 6.6 μM). AZA1 did not block K+ current of the closely related EAG1 channel. Collectively, these data suggest that the AZAs physically block the K+ conductance pathway of hERG1 channels by occluding the cytoplasmic mouth of the open pore. Although the concentrations necessary to block hERG channels are relatively high, AZA-induced blockage may prove to contribute to the toxicological properties of the AZAs. PMID:22856456

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

    Science.gov (United States)

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

    2016-06-01

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

  6. Marine algal toxin azaspiracid is an open-state blocker of hERG potassium channels.

    Science.gov (United States)

    Twiner, Michael J; Doucette, Gregory J; Rasky, Andrew; Huang, Xi-Ping; Roth, Bryan L; Sanguinetti, Michael C

    2012-09-17

    Azaspiracids (AZA) are polyether marine dinoflagellate toxins that accumulate in shellfish and represent an emerging human health risk. Although human exposure is primarily manifested by severe and protracted diarrhea, this toxin class has been shown to be highly cytotoxic, a teratogen to developing fish, and a possible carcinogen in mice. Until now, AZA's molecular target has not yet been determined. Using three independent methods (voltage clamp, channel binding assay, and thallium flux assay), we have for the first time demonstrated that AZA1, AZA2, and AZA3 each bind to and block the hERG (human ether-à-go-go related gene) potassium channel heterologously expressed in HEK-293 mammalian cells. Inhibition of K(+) current for each AZA analogue was concentration-dependent (IC(50) value range: 0.64-0.84 μM). The mechanism of hERG channel inhibition by AZA1 was investigated further in Xenopus oocytes where it was shown to be an open-state-dependent blocker and, using mutant channels, to interact with F656 but not with Y652 within the S6 transmembrane domain that forms the channel's central pore. AZA1, AZA2, and AZA3 were each shown to inhibit [(3)H]dofetilide binding to the hERG channel and thallium ion flux through the channel (IC(50) value range: 2.1-6.6 μM). AZA1 did not block the K(+) current of the closely related EAG1 channel. Collectively, these data suggest that the AZAs physically block the K(+) conductance pathway of hERG1 channels by occluding the cytoplasmic mouth of the open pore. Although the concentrations necessary to block hERG channels are relatively high, AZA-induced blockage may prove to contribute to the toxicological properties of the AZAs.

  7. Voltage gated sodium and calcium channel blockers for the treatment of chronic inflammatory pain.

    Science.gov (United States)

    Rahman, Wahida; Dickenson, Anthony H

    2013-12-17

    The inflammatory response is a natural response of the body that occurs immediately following tissue damage, which may be due to injury, infection or disease. The acute inflammatory response is an essential mechanism that promotes healing and a key aspect is the ensuing pain, which warns the subject to protect the site of injury. Thus, it is common to see a zone of primary sensitization as well as consequential central sensitization that generally, is maintained by a peripheral drive from the zone of tissue injury. Inflammation associated with chronic pain states, such as rheumatoid and osteoarthritis, cancer and migraine etc. is deleterious to health and often debilitating for the patient. Thus there is a large unmet clinical need. The mechanisms underlying both acute and chronic inflammatory pain are extensive and complex, involving a diversity of cell types, receptors and proteins. Among these the contribution of voltage gated sodium and calcium channels on peripheral nociceptors is critical for nociceptive transmission beyond the peripheral transducers and changes in their distribution, accumulation, clustering and functional activities have been linked to both inflammatory and neuropathic pain. The latter has been the main area for trials and use of drugs that modulate ion channels such as carbamazepine and gabapentin, but given the large peripheral drive that follows tissue damage, there is a clear rationale for blocking voltage gated sodium and calcium channels in these pain states. It has been hypothesized that pain of inflammatory origin may evolve into a condition that resembles neuropathic pain, but mixed pains such as low back pain and cancer pain often include elements of both pain states. This review considers the therapeutic potential for sodium and calcium channel blockers for the treatment of chronic inflammatory pain states. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Association between calcium channel blockers and breast cancer: a meta-analysis of observational studies.

    Science.gov (United States)

    Chen, Qi; Zhang, Qianwen; Zhong, Fei; Guo, Shiwei; Jin, Zhichao; Shi, Wentao; Chen, Chen; He, Jia

    2014-07-01

    To investigate the association between calcium channel blockers (CCBs) and increased risk of breast cancer. Using terms related to breast cancer and CCB, we searched PubMed, Embase, and Web of Science for studies on CCB use and the associated risk of breast cancer published before July 2013. Two evaluators independently selected observational studies on the basis of predetermined selection criteria, and 11 studies were included in the meta-analysis. Summary estimates were obtained using fixed-effects or random-effects models as appropriate, and subgroup analyses, sensitivity analyses, and publication bias tests were performed. Our meta-analysis consisted of 11 studies, including four case-controls, two nested case-controls, and five cohort studies. The odds ratios (ORs) of the association between CCB use and breast cancer were 1.11 (95% confidence interval [CI] 0.93-1.33) overall, 1.04 (95%CI 0.92-1.18) for prospective studies, and 1.33 (95%CI 0.79-2.25) for retrospective studies. There was a positive association between immediate-release CCB use and risk of breast cancer (OR 1.88, 95%CI 1.37-2.60). There is no evidence that CCB use is associated with an increased risk of breast cancer. However, there may be a positive association between immediate-release CCB use and risk of breast cancer, but given the current preference for use of sustained-release CCB, the potential clinical impact of this association is limited. Copyright © 2014 John Wiley & Sons, Ltd.

  9. The association between calcium channel blocker use and prostate cancer outcome.

    Science.gov (United States)

    Poch, Michael A; Mehedint, Diana; Green, Dawn J; Payne-Ondracek, Rochelle; Fontham, Elizabeth T H; Bensen, Jeannette T; Attwood, Kristopher; Wilding, Gregory E; Guru, Khurshid A; Underwood, Willie; Mohler, James L; Heemers, Hannelore V

    2013-06-01

    Epidemiological studies indicate that calcium channel blocker (CCB) use is inversely related to prostate cancer (PCa) incidence. The association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) and outcome after RP was examined. Medication use, PCa aggressiveness and post-RP outcome were retrieved from a prospectively populated database that contains clinical and outcome for RP patients at Roswell Park Cancer Institute (RPCI) from 1993 to 2010. The database was queried for anti-hypertensive medication use at diagnosis for patients with ≥1 year follow-up. Recurrence was defined using NCCN guidelines. Chi-Square tests assessed the relationship between CCB use and PCa aggressiveness. Cox regression models compared the distribution of progression-free survival (PFS) and overall survival (OS) with adjustment for covariates. Results for association between CCB usage and PCa aggressiveness were validated using data from the population-based North Carolina-Louisiana Prostate Cancer Project (PCaP). 48%, 37%, and 15% of RPCI's RP patients (n = 875) had low, intermediate, and high aggressive PCa, respectively. 104 (11%) had a history of CCB use. Patients taking CCBs were more likely to be older, have a higher BMI and use additional anti-hypertensive medications. Diagnostic PSA levels, PCa aggressiveness, and margin status were similar for CCB users and non-users. PFS and OS did not differ between the two groups. Tumor aggressiveness was associated with PFS. CCB use in the PCaP study population was not associated with PCa aggressiveness. CCB use is not associated with PCa aggressiveness at diagnosis, PFS or OS. Copyright © 2012 Wiley Periodicals, Inc.

  10. Calcium channel blockers and risk of breast cancer: a meta-analysis of 17 observational studies.

    Science.gov (United States)

    Li, Wen; Shi, Qi; Wang, Weibing; Liu, Jianrong; Li, Qi; Hou, Fenggang

    2014-01-01

    Studies on the association between the use of calcium channel blockers (CCBs) and breast cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on the evidence from observational studies. We searched PubMed, MEDLINE, EMBASE and the Cochrane Library for relevant studies published up to and including December 31, 2013. We calculated pooled risk ratios (RRs) for cancer risk. A total of 17 studies (9 cohort studies, 8 case-control studies) were selected for further study. These studies included 149,607 female subjects, of which 53,812 were CCBs users, who were followed for 2-16 years. The risks of breast cancer among patients receiving CCBs were significantly different for the pooled RRs (95% confidence interval) of cohort studies 1.08 (0.95, 1.20) and case-control studies 0.98 (0.86, 1.09). Differences were also noted for cancer risk, for CCBs use of 5 years 1.01 (0.74, 1.28), as well as for ever used 1.08 (0.95, 1.20), and for current use 1.13 (0.83, 1.42). The RR for studies longer than 10 years was 1.71 (1.01, 2.42), and for studies evaluating nifedipine was 1.10 (0.87, 1.33) and diltiazem was 0.75 (0.40, 1.10). The long-term use of CCBs appears to have a significant relationship with breast cancer. Well-designed clinical trials are needed to optimize the doses and types of these drugs needed to minimize their carcinogenic potential.

  11. Calcium channel blockers and risk of breast cancer: a meta-analysis of 17 observational studies.

    Directory of Open Access Journals (Sweden)

    Wen Li

    Full Text Available PURPOSE: Studies on the association between the use of calcium channel blockers (CCBs and breast cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on the evidence from observational studies. METHODS: We searched PubMed, MEDLINE, EMBASE and the Cochrane Library for relevant studies published up to and including December 31, 2013. We calculated pooled risk ratios (RRs for cancer risk. RESULTS: A total of 17 studies (9 cohort studies, 8 case-control studies were selected for further study. These studies included 149,607 female subjects, of which 53,812 were CCBs users, who were followed for 2-16 years. The risks of breast cancer among patients receiving CCBs were significantly different for the pooled RRs (95% confidence interval of cohort studies 1.08 (0.95, 1.20 and case-control studies 0.98 (0.86, 1.09. Differences were also noted for cancer risk, for CCBs use of 5 years 1.01 (0.74, 1.28, as well as for ever used 1.08 (0.95, 1.20, and for current use 1.13 (0.83, 1.42. The RR for studies longer than 10 years was 1.71 (1.01, 2.42, and for studies evaluating nifedipine was 1.10 (0.87, 1.33 and diltiazem was 0.75 (0.40, 1.10. CONCLUSIONS: The long-term use of CCBs appears to have a significant relationship with breast cancer. Well-designed clinical trials are needed to optimize the doses and types of these drugs needed to minimize their carcinogenic potential.

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

    Science.gov (United States)

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

    2016-01-08

    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. This is a population-based cohort study in patients exposed to CCBs from across the UK, using two comparison cohorts: (1) patients with no exposure to CCB (non-CCB) matched on age and gender and (2) unmatched patients unexposed to CCB and at least one other antihypertensive (AHT) prescription. Cancer incidence rates computed in the exposed and the two unexposed groups were compared using HRs and 95% CIs obtained from multivariate Cox regression analyses. Overall, 150,750, 557,931 and 156,966 patients were included, respectively, in the CCB, non-CCB and AHT cohorts. Crude cancer incidence rates per 1000 person-years were 16.51, 15.75 and 10.62 for the three cohorts, respectively. Adjusted HRs (CI) for all cancers comparing CCB, non-CCB and AHT cohorts were 0.88 (0.86 to 0.89) and 1.01 (0.98 to 1.04), respectively. Compared to the AHT cohort, adjusted HRs (CI) for breast, prostate and colon cancer for the CCB cohort were 0.95 (0.87 to 1.04), 1.07 (0.98 to 1.16) and 0.89 (0.81 to 0.98), respectively. Analyses by duration of exposure to CCB did not show excess risk. This large population-based study provides strong evidence that CCB use is not associated with an increased risk of cancer. The analyses yielded robust results across all types of cancer and different durations of exposure to CCBs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Enhancement of Tissue Expansion by Calcium Channel Blocker: A preliminary study

    Directory of Open Access Journals (Sweden)

    Aktas Alper

    2003-10-01

    Full Text Available Abstract Background Reconstruction of the defects after surgical resection of tumors is one of the important issues in surgical oncology. It is essential that the defect should be covered with a tissue quite similar to the original one and is best achieved by harvesting tissue from an area adjacent to the defect. Tissue expansion is one of the most frequently used reconstructive techniques. A number of studies evaluated blood circulation, capsule formation, tissue tolerance, histomorphological changes and complications of expander placement. However, only a few attempted to enhance tissue expansion. This study we aimed to evaluate verapamil, a calcium channel blocker, to enhance tissue expansion. Material and method Twelve New Zealand rabbits weighing between 900 gm and 1200 gm were assigned into study and control groups. High volume expanders (100, 200 or 300 cc were placed into the subcutaneous tissue. Rabbits in the study group received verapamil. Expanders in the control group were inflated every three days to achieve same pressure as the study group. The size of the flaps was assessed by applying pressure on tip of the flap to demonstrate the contraction. Histopathological examinations were performed. Results By administering liquid earlier and more quickly less flap retraction was observed in the study group. In the control group expanders were exposed in two rabbits while no complication occurred in the study group. Following extraction of the expanders, the flaps were elevated and less retraction was observed in the study group compared to controls. Conclusion Verapamil is safe when used topically and provides less retracted flaps. It can be suggested that verapamil acts on the myofibroblasts in the capsule around tissue expanders and thus increases efficiency of the expanders.

  14. Renoprotective effects of mineralocorticoid receptor blockers in patients with proteinuric kidney diseases.

    Science.gov (United States)

    Morales, Enrique; Millet, Victor Gutiérrez; Rojas-Rivera, Jorge; Huerta, Ana; Gutiérrez, Eduardo; Gutiérrez-Solís, Elena; Egido, Jesús; Praga, Manuel

    2013-02-01

    Several studies have demonstrated a short-term antiproteinuric effect of mineralocorticoid receptor blockers (MRB) on proteinuric kidney diseases, but no information is available about the long-term persistence (>1 year) of such reduction in proteinuria and the long-term effects of MRB on renal function. We prospectively studied the effects of adding spironolactone (25 mg/day) to 87 patients who maintained proteinuria higher than 1 g/day in spite of renin-angiotensin system blockade. The mean follow-up was 25 ± 15 (1-84) months. Estimated glomerular filtration rate (eGFR) showed an acute fall in the first month of treatment (5.1 ± 9.4 mL/min/1.73 m(2)), but it remained stable thereafter (+0.04 ± 0.7 mL/min/1.73 m(2)/month), with a significant difference with respect to the eGFR slope during the 12-month pre-treatment period. The initial eGFR fall predicted a more stable course of renal function, the higher the eGFR initial fall, the better the long-term evolution of eGFR. Proteinuria showed an important and sustained reduction since the first month of treatment. At the end of follow-up, it had decreased by 61% (43-77%) with respect to baseline values. The antiproteinuric and renoprotective influence of spironolactone was also observed in diabetic patients and in patients with renal function impairment, although tolerance was poorer among the latter. Spironolactone induces an initial acute fall in eGFR that predicts a later favourable influence on the course of renal function and a remarkable and sustained reduction in proteinuria.

  15. Traumatic brain injury and β-blockers: not all drugs are created equal.

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    Schroeppel, Thomas J; Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Clement, L Paige; Croce, Martin A; Fabian, Timothy C

    2014-02-01

    Dysautonomia in traumatic brain injury patients may contribute to secondary injury. We hypothesize that propranolol is the best β-blocker (BB) to block the excess catecholamines and improve mortality in this patient population. Patients with traumatic brain injury admitted during a 48-month period who received BB were compared with those who did not after excluding patients who received preinjury BB, deaths within 48 hours, and head Abbreviated Injury Scale (AIS) score of less than 3 or greater than 5. In addition, propranolol was also compared with all other BBs. A total of 1,755 patients with traumatic brain injury were identified during the study period after exclusions. Patients who received BB (427) were older (49 years vs. 40 years; p < 0.0001), were more severely injured (Injury Severity Score [ISS], 30 vs. 24; p < 0.001), and had a more severe head injury (head AIS score, 4.2 vs. 4.0; p < 0.001). By univariate analysis, BB patients had a higher mortality (13% vs. 6%; p < 0.001); after adjusted analysis, no difference was identified (adjusted odds ratio, 0.850; 95% confidence interval, 0.536-1.348). Seventy-eight patients (18%) received propranolol during the study period. Propranolol patients were younger (30 years vs. 53 years; p < 0.001) but more severely injured (ISS, 33 vs. 29; p = 0.01; head AIS, 4.5 vs. 4.2; p < 0.001), with longer stay (44 days vs. 26 days, p < 0.001). Mortality was less in the propranolol group (3% vs. 15%, p = 0.002). Adjusted analysis confirmed the protective effect of propranolol (adjusted odds ratio, 0.199; 95% confidence interval, 0.043-0.920). Propranolol is the best BB to limit secondary injury and decrease mortality in patients with traumatic brain injury. Therapeutic, study level III.

  16. A controlled study of a serotonin reuptake blocker, zimelidine, in the treatment of chronic pain.

    Science.gov (United States)

    Gourlay, G K; Cherry, D A; Cousins, M J; Love, B L; Graham, J R; McLachlan, M O

    1986-04-01

    Zimelidine inhibits the central neuronal reuptake of serotonin and has undergone clinical evaluation as an antidepressant. Twenty patients with chronic pain of non-malignant origin (mean duration 15.8 years) were entered into a double blind cross-over study of the analgesic efficacy of zimelidine and placebo. The duration of each treatment phase was 6 weeks and there was a comprehensive assessment of each patient prior to the commencement and at the completion of the study, during a brief period of hospitalisation. Zimelidine was superior (P less than 0.05) to placebo with respect to pain relief based on a global assessment (by the clinical investigators) performed at the completion of each treatment phase. However, there was no significant difference in analgesic efficacy between the zimelidine and placebo treatment phases based on the following criteria: (a) changes in the minimum effective blood concentration of pethidine necessary to provide pain relief in each patient, measured during a pethidine infusion of 1.67 mg/min for 60 min; (b) changes in pain scores estimated by patients using the visual analogue pain scale (VAPS); (c) changes in patients' estimates of pain intensity associated with various daily activities. Significant pain relief was apparent within 2-3 days in those patients who had a beneficial effect, which contrasts with the documented 3-4 weeks for maximal antidepressant effects. The results of this study suggest that serotonin reuptake blockers do not provide consistent pain relief in patients with chronic pain, but may contribute an analgesic effect in the treatment of some patients.

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

    Science.gov (United States)

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

    2016-07-05

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

  18. Induction of parturition in the bitch with the progesterone-receptor blocker aglépristone.

    Science.gov (United States)

    Baan, M; Taverne, M A M; Kooistra, H S; de Gier, J; Dieleman, S J; Okkens, A C

    2005-04-15

    The triggering mechanism for parturition in the bitch remains unclear. Consequently, the development of drugs to successfully induce parturition in the dog has been difficult. The aim of this study was to evaluate the efficacy of the progesterone-receptor blocker aglépristone for the induction of parturition in beagle bitches. The course of parturition was therefore investigated in six parturitions induced by aglépristone and in six spontaneous parturitions. In addition, data were collected on pup survival and growth rates. Aglépristone was administered twice with a 9h interval on day 58 of pregnancy. If parturition did not proceed a standard intervention protocol was applied. Expulsion of the first pup occurred between 32 and 56 h after the first treatment with aglépristone, at which time the plasma progesterone concentration was still elevated. Accordingly, the gestation length of the bitches in the induced group (59.5+/-0.2 days) was significantly shorter than that of the spontaneously whelping bitches (62.2+/-0.5 days). The expulsion phase length, the inter-pup interval, the number of puppies born dead, and the number of clinical interventions needed during parturition did not significantly differ between the spontaneously whelping and the induced group. Pup survival and mean birth weights in the two groups did not differ significantly and aglépristone treatment had no significant influence on the growth rates. The results of this study show that aglépristone is an effective drug which can be used safely for the induction of parturition in the dog.

  19. [Controversies and dilemmas on the use of beta-blockers in treatment of associated cardiovascular disease in patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    Pescaru, Camelia; Tudorache, Voicu; Oancea, Cristian

    2010-01-01

    In the last decade, chronic obstructive pulmonary disease (COPD) has been considered a syndrome with multiple phenotypical facets and systemic components. Chronic diseases are associated, in time, with several comorbidities. Cardiovascular disease represents the most common comorbidity in COPD, increases its handicap and mortality indices. Most entities associated with cardiovascular disease require treatment with beta-blockers. However, beta-blockers are a "two-edged sword" when administered in obstructive pulmonary disorder. The use of beta-blockers should be assessed by their action on three areas: their effect on FEV1, their effect on bronchial hyperreactivity, the result obtained when additionally administering beta-agonists. The result of beta-blocker administration is influenced by the involvement of several other factors: the cardioselectivity of the beta-blocker, the dosage, the concomitant administration of beta-agonists, the stage of the disease (stable or exacerbation of COPD), smoker status etc. Their administration under strict monitoring results in a decreased morbidity and mortality, including in patients who had undergone cardiovascular surgery. The overall conclusion is that beta-blockers may be administered in COPD associated with cardiac comorbidity, but this administration requires utmost care.

  20. Tachyphylaxis to the inhibitory effect of L-type channel blockers on ACh-induced [Ca2+]i oscillations in porcine tracheal myocytes.

    Science.gov (United States)

    Chung, Wen-Shuo; Farley, Jerry M

    2007-01-01

    Discrepancies about the role of L-type voltage-gated calcium channels (VGCC) in acetylcholine (ACh)-induced [Ca(2+)](i) oscillations in tracheal smooth muscle cells (TSMCs) have been seen in recent reports. We demonstrate here that ACh-induced [Ca(2+)](i) oscillations in TMCS were reversibly inhibited by three VGCC blockers, nicardipine, nifedipine and verapamil. Prolonged (several minutes) application of VGCC blockers, led to tachyphylaxis; that is, [Ca(2+)](i) oscillations resumed, but at a lower frequency. Brief (15-30 s) removal of VGCC blockers re-sensitized [Ca(2+)](i) oscillations to inhibition by the agents. Calcium oscillations tolerant to VGCC blockers were abolished by KB-R7943, an inhibitor of the reverse mode of Na(+)/Ca(2+) exchanger (NCX). KB-R7943 alone also abolished ACh-induced [Ca(2+)](i) oscillations. Enhancement of the reverse mode of NCX via removing extracellular Na(+) reversed inhibition of ACh-induced [Ca(2+)](i) oscillations by VGCC blockers. Inhibition of non-selective cation channels using Gd(3+) slightly reduced the frequency of ACh-induced [Ca(2+)](i) oscillations, but did not prevent the occurrence of tachyphylaxis. Altogether, these results suggest that VGCC and the reverse mode of NCX are two primary Ca(2+) entry pathways for maintaining ACh-induced [Ca(2+)](i) oscillations in TSMCs. The two pathways complement each other, and may account for tachyphylaxis of ACh-induced [Ca(2+)](i) oscillations to VGCC blockers.

  1. Calcium channel blockers reduce oxaliplatin-induced acute neuropathy: a retrospective study of 69 male patients receiving modified FOLFOX6 therapy.

    Science.gov (United States)

    Tatsushima, Yoko; Egashira, Nobuaki; Narishige, Yuri; Fukui, Shiori; Kawashiri, Takehiro; Yamauchi, Yui; Oishi, Ryozo

    2013-02-01

    Oxaliplatin-based chemotherapy has been widely used for colorectal cancer. However, it causes severe acute and chronic peripheral neuropathies. Recently, we reported that calcium channel blockers prevent the oxaliplatin-induced cold hyperalgesia in rats. The purpose of this study was to determine whether the treatment with calcium channel blockers prevents the peripheral neuropathy during oxaliplatin therapy. The electronic medical charts for patients who received modified FOLFOX6 regimen from January 2008 to December 2010 were evaluated. Of the 200 patients who received modified FOLFOX6 therapy, 84 patients were excluded due to the exclusion criteria. Calcium channel blockers had been taken by 26 of 69 male patients, but only three of 47 female patients. Therefore, in the present analysis, the male data of the groups with and without calcium channel blockers (n=26 and 43, respectively) were compared. The cumulative incidence curve of acute neuropathy was significantly lower in the group with calcium channel blockers (P=0.0438, log-rank test), whereas there was no difference between these groups in the cumulative incidence curve of chronic neuropathy (P=0.4919, log-rank test). The present study indicated that calcium channel blockers inhibit the development of acute peripheral neuropathy in patients receiving modified FOLFOX6 therapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

    Horninger, W; Bartsch, G

    2002-09-01

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

  3. Sexual Dysfunction Related to Drugs: a Critical Review. Part V: α-Blocker and 5-ARI Drugs.

    Science.gov (United States)

    La Torre, A; Giupponi, G; Duffy, D; Conca, A; Cai, T; Scardigli, A

    2016-01-01

    Sexual dysfunction is a potential side effect of BPH (benign prostatic hyperplasia) and LUTS (lower urinary tract symptoms) drugs: this article is a critical review of the current literature. Many studies have been published on this topic. Methodological flaws limit the conclusions of these studies, mainly because of the lack of diagnostic criteria for ejaculatory and sexual desire dysfunction. Few of these studies are RCTs. The α-blocker (also called α1-adrenergic antagonist, alpha-adrenoceptor antagonist, alpha-blocker or AB) and 5-ARI (also called 5α-reductase inhibitor or testosterone-5-alpha reductase inhibitor) drugs can in particular cause erectile dysfunction, ejaculatory disorders and reduction of sexual desire. The sexual side effect profile of these drugs is different. Among the α-blockers, silodosin appears have the highest incidence of ejaculatory disorders. Persistent sexual side effects after discontinuation of finasteride has recently been reported, however further studies are needed to clarify the true incidence and the significance of this finding. It is desirable that future studies include validated tools to assess and diagnose sexual dysfunction induced by these medications, especially for ejaculation and sexual desire disorders. Only a small amount of research has intentionally set out to investigate sexual dysfunction caused by α-blocker and 5-ARI drugs: studies to specifically assess sexual dysfunction induced by these drugs are needed. Further studies are also needed to assess in the long term the role of combined therapy of phosphodiesterase type 5 inhibitors and α-blockers or 5-ARIs in treating LUTS/BPH. This study was conducted in 2014 using the paper and electronic resources of the library of the "Azienda Provinciale per i Servizi Sanitari (APSS)" in Trento, Italy (http://atoz.ebsco.com/Titles/2793). The library has access to a wide range of databases including DYNAMED, MEDLINE Full Text, CINAHL Plus Full Text, The Cochrane

  4. Differential Effects of β-Blockers, Angiotensin II Receptor Blockers, and a Novel AT2R Agonist NP-6A4 on Stress Response of Nutrient-Starved Cardiovascular Cells.

    Directory of Open Access Journals (Sweden)

    Abuzar Mahmood

    Full Text Available In order to determine differences in cardiovascular cell response during nutrient stress to different cardiovascular protective drugs, we investigated cell responses of serum starved mouse cardiomyocyte HL-1 cells and primary cultures of human coronary artery vascular smooth muscles (hCAVSMCs to treatment with β-blockers (atenolol, metoprolol, carvedilol, nebivolol, 3 μM each, AT1R blocker losartan (1 μM and AT2R agonists (CGP42112A and novel agonist NP-6A4, 300 nM each. Treatment with nebivolol, carvedilol, metoprolol and atenolol suppressed Cell Index (CI of serum-starved HL-1 cells (≤17%, ≤8%, ≤15% and ≤15% respectively as measured by the Xcelligence Real-Time Cell Analyzer (RTCA. Conversely, CI was increased by Ang II (≥9.6%, CGP42112A (≥14%, and NP-6A4 (≥25% respectively and this effect was blocked by AT2R antagonist PD123319, but not by AT1R antagonist losartan. Thus, the CI signature for each drug could be unique. MTS cell proliferation assay showed that NP-6A4, but not other drugs, increased viability (≥20% of HL-1 and hCAVSMCs. Wheat Germ Agglutinin (WGA staining showed that nebivolol was most effective in reducing cell sizes of HL-1 and hCAVSMCs. Myeloid Cell Leukemia 1 (MCL-1 is a protein critical for cardiovascular cell survival and implicated in cell adhesion. β-blockers significantly suppressed and NP-6A4 increased MCL-1 expression in HL-1 and hCAVSMCs as determined by immunofluorescence. Thus, reduction in cell size and/or MCL-1 expression might underlie β-blocker-induced reduction in CI of HL-1. Conversely, increase in cell viability and MCL-1 expression by NP-6A4 through AT2R could have resulted in NP-6A4 mediated increase in CI of HL-1. These data show for the first time that activation of the AT2R-MCL-1 axis by NP-6A4 in nutrient-stressed mouse and human cardiovascular cells (mouse HL-1 cells and primary cultures of hCAVSMCs might underlie improved survival of cells treated by NP-6A4 compared to other

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Factors associated with β-blocker initiation and discontinuation in a population-based cohort of seniors newly diagnosed with heart failure

    Directory of Open Access Journals (Sweden)

    Girouard C

    2016-09-01

    Full Text Available Catherine Girouard,1–3 Jean-Pierre Grégoire,1–3 Paul Poirier,2,4 Jocelyne Moisan1–3 1Chair on Adherence to Treatments, Université Laval, 2Faculty of Pharmacy, Université Laval, 3Population Health and Optimal Health Practices Research Unit, CHU de Québec Research Center, 4Quebec Heart and Lung Institute-Université Laval, Quebec City, QC, Canada Purpose: β-Blockers (bisoprolol, carvedilol, and metoprolol are the cornerstone of heart failure (HF management. The incidence rate of β-blocker initiation and discontinuation and their associated factors among seniors with a first HF diagnosis were assessed.Methods: A population-based inception cohort study that included all individuals aged ≥65 years with a first HF diagnosis in Quebec was conducted. β-Blockers initiation among 91,131 patients who were not using β-blockers at the time of HF diagnosis and discontinuation among those who initiated a β-blocker after HF diagnosis were assessed. Stepwise Cox regression analyses were used to calculate hazard ratios (HR and to identify factors associated with β-blocker initiation and discontinuation.Results: After HF diagnosis, 32,989 (36.2% individuals initiated a β-blocker. Of these, 15,408 (46.7% discontinued their β-blocker during the follow-up. Individuals more likely to initiate a β-blocker were those diagnosed in a recent calendar year (2009: HR, 2.11; 95% confidence interval [CI], 2.00–2.23 and diagnosed by a cardiologist (HR, 1.38; 95% CI, 1.34–1.42. Individuals less likely to initiate were those aged ≥90 years (HR, 0.65; 95% CI, 0.61–0.68 and those with chronic obstructive pulmonary disease (HR, 0.66; 95% CI, 0.64–0.68. Individuals more likely to discontinue were those with more than nine medical consultations (HR, 1.14; 95% CI, 1.10–1.18 and those with dementia (HR, 1.13; 95% CI, 1.01–1.27. Individuals less likely to discontinue were those diagnosed in a recent calendar year (2009: HR 0.74; 95% CI, 0.65–0.82 and

  7. The influence of radiation sterilisation on some {beta}-blockers in the solid state

    Energy Technology Data Exchange (ETDEWEB)

    Marciniec, B. [Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 6 Gruwaldzka Str., 60-780 Poznan (Poland); Ogrodowczyk, M., E-mail: mogrodo@ump.edu.pl [Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 6 Gruwaldzka Str., 60-780 Poznan (Poland); Czajka, B.; Hofman, M. [Department of Cooridinational Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznan (Poland)

    2011-02-20

    Research highlights: {yields} Six {beta}-blockers (acebutolol, alprenolol, atenolol, metoprolol, pindolol, propranolol) in solid phase were exposed to the ionising radiation by e-beam in doses from 25 to 400 kGy. {yields} To establish the effects of irradiation on their physico-chemical properties, the compounds were then analysed by DSC, SEM, XRD and FT-IR. {yields} For alprenolol, propranolol and metoprolol linear relations were found between the irradiation dose and the decrease in the melting point (r = 0.9446-0.9864). {yields} No changes were observed in the FT-IR spectra and in the SEM images of the compounds studied. - Abstract: Six derivatives of aryloxyalkylaminopropanol of known {beta}-adrenolytic activity (acebutolol, alprenolol, atenolol, metoprolol, pindolol, propranolol) in solid phase were exposed to the ionising radiation generated by e-beam of high-energy electrons from an accelerator ({approx}10 MeV) in doses from 25 to 400 kGy. To establish the effects of irradiation on their physico-chemical properties, the compounds were then analysed by differential scanning calorimetry (DSC), scanning electron microscope (SEM), X-ray diffraction (XRD) and FT-IR spectrometry. The standard sterilisation dose (25 kGy) was found to cause no changes in only one derivative - acebutolol, whereas in the other derivatives the irradiation caused colour changes, differences in X-ray diffraction patterns and in the character of DSC curves, including a decrease in the melting point. For each derivative one clear peak corresponding to the process of melting was observed and its position shifted towards lower temperatures with increasing dose of irradiation. For all compounds studied the value of the shift was between 0.1 and 1.0 {sup o}C. For alprenolol, propranolol and metoprolol linear relations were found between the irradiation dose and the decrease in the melting point, described by the correlation coefficient (between 0.9446 and 0.9864). No changes were observed in

  8. The effect of the NMDA channel blocker memantine on salicylate-induced tinnitus in rats.

    Science.gov (United States)

    Ralli, M; Troiani, D; Podda, M V; Paciello, F; Eramo, S L M; de Corso, E; Salvi, R; Paludetti, G; Fetoni, A R

    2014-06-01

    Short-term tinnitus develops shortly after the administration of a high dose of salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA) currents in spiral ganglion neurons, it may play a vital role in tinnitus by amplifying NMDA-mediated neurotransmission. The aim of this study was to determine whether systemic treatment with a NMDA channel blocker, memantine, could prevent salicylate-induced tinnitus in animals. Additional experiments were performed to evaluate the effect of memantine on the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in hearing function. Thirty-six rats were divided into 3 groups and treated daily for four consecutive days. One group (n = 12) was injected with salicylate (300 mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and the third group (n = 12) was injected with salicylate and memantine. All rats were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first drug administration and 24 h post treatment; tinnituslike behaviour was assessed with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the last salicylate treatment. Memantine did not cause a significant change in GPIAS. Combined injection of salicylate and memantine significantly attenuated GPIAS tinnitus-like behaviour at 48 hours after the first injection. None of the treatments induced permanent threshold shifts in the ABR and DPOAE, which recovered completely within one day post treatment. Animals treated with salicylate plus memantine showed results comparable to animals treated with salicylate alone, confirming that there is no effect of memantine on DPOAE which reflects OHC function. The

  9. Cost of tumor necrosis factor blockers per patient with rheumatoid arthritis in a multistate Medicaid population

    Directory of Open Access Journals (Sweden)

    Bonafede M

    2014-09-01

    Full Text Available Machaon Bonafede,1 George J Joseph,2 Neel Shah,2 Nicole Princic,1 David J Harrison2 1Truven Health Analytics, Cambridge, MA, 2Amgen Inc., Thousand Oaks, CA, USA Background: The purpose of this study was to estimate the annual cost per treated patient for the tumor necrosis factor (TNF blockers, etanercept, adalimumab, and infliximab in rheumatoid arthritis (RA patients covered by Medicaid. Methods: The MarketScan Medicaid Multistate Database was used to identify adult RA patients who used etanercept, adalimumab, or infliximab (index agents from 2007 to 2011. The index date was the first claim preceded by 180 days and followed by 360 days of continuous enrollment. Patients with other conditions for which these agents are approved by the US Food and Drug Administration were excluded. “Continuing” patients had one or more pre-index claim for their index biologic, and "new" patients did not. Cost per treated patient was calculated in the 360 day post-index period for each index agent as the total index drug and administration cost to the payer and the costs of switched-to agents divided by the number of patients who received the index agent. Results: A total of 1,085 patients met the study criteria. Forty-eight percent received etanercept (n=521; 37% received adalimumab (n=405; and 15% received infliximab (n=159. Patient characteristics were similar across groups (mean age 47.4 years, 83% female. The annual cost per treated patient was lowest for etanercept ($18,466, followed by adalimumab ($20,983 and infliximab ($26,516. For all agents, annual costs were lower for new patients ($17,996 for etanercept, $18,992 for adalimumab, and $24,756 for infliximab than for continuing patients ($19,004 for etanercept, $24,438 for adalimumab, and $28,127 for infliximab. Conclusion: Etanercept had lower costs per treated patient than adalimumab or infliximab in both new and continuing Medicaid enrollees with RA. Keywords: cost, tumor necrosis factor

  10. Scientific research related to calcium channel blockers poisoning: Bibliometric analysis in Scopus, 1968-2012.

    Science.gov (United States)

    Zyoud, S H; Al-Jabi, S W; Sweileh, W M; Waring, W S

    2015-11-01

    Calcium channel blockers (CCBs) were the most common agents associated with a significant morbidity and mortality rate. The main objective of this study was to examine the publication pattern related to CCBs poisoning at the global level using bibliometric analysis of articles published in SciVerse Scopus online database. Data were searched for documents that contained specific words regarding CCB poisoning as keywords in the title. No time period limitations were specified in the search regarding the starting year. The ending date of the search was 31 December 2012. The criteria were met by 713 publications from 53 countries. The largest number of articles associated with CCBs was from the United States (30%), followed by the United Kingdom (7.4%), Japan (6%), and Germany (5.6%). No data related to CCBs were published from 159 (75%) of 212 countries registered in World Bank online database. There was no correlation between the number of published articles in the country and its population size (r = 0.03, p > 0.926). United Kingdom and Australia were the leading countries in terms of number of CCBs publications per million inhabitants (0.83 and 0.82 articles per million inhabitants, respectively), followed by the United States (0.68). Countries with a large population, such as India, tended to rank relatively low (0.01 articles per million inhabitants). The total number of citations at the time of data analysis (23 October 2014) was 6462, with an average of 9.1 citations per document. The highest median (interquartile range) number of citations was 8 (8-18) for the United States, followed by 6 (1-21) for Australia, 5 (1-15) for the United Kingdom, and 5 (1-24) for Canada. The h-index of the retrieved documents was 37. Scientific production on CCBs poisoning is increasing; nonetheless, the international collaboration is still rare. The amount of CCBs-based research activity was low or not available in most countries. More regional epidemiological studies are

  11. Risk of new-onset diabetes mellitus associated with beta-blocker treatment for hypertension.

    Science.gov (United States)

    Fonseca, Vivian; Sharma, Puza P; Shah, Manan; Deedwania, Prakash

    2011-04-01

    This study investigated the risk of new-onset diabetes (NOD) among hypertensive patients initiating carvedilol therapy vs other beta-blocker (BB) therapy in a clinical practice setting. Patients aged ≥18 years with ≥1 pharmacy claim for a BB of interest (carvedilol immediate-release [IR]/controlled-release [CR], atenolol, metoprolol succinate, or metoprolol tartrate) were identified in the IMS LifeLink Health Plan Claims Database. Index date was the first chronologically occurring prescription for any BB during the enrollment period (July 1, 2000-December 31, 2007). Patients had to be continuously eligible to receive healthcare services 6 months prior to and a minimum of 3 months after index date and have ≥1 diagnostic code for hypertension (ICD-9-CM: 401.xx-405.xx) during this time frame. Patients were excluded for having a diagnosis of diabetes mellitus (ICD-9-CM: 250.xx) and/or prescription for antidiabetic therapy in the 6 months prior to and/or 3 months after index date. Eligible patients were propensity-score matched in a 1:3 ratio (carvedilol : other BBs). Mean duration of follow-up was 12.8 and 14.8 months for the carvedilol group and other BB group, respectively. Primary outcome of interest was presence and timing of NOD. Among 3084 patients in the carvedilol group and 9252 in the other BB group, mean age was 56 years, with 54% male. NOD rate was 3.16 per 100 person-years for carvedilol patients vs 3.36 for patients in the other BB group (NS). Risk of NOD was similar between groups (HR 0.971, 95% CI: 0.78, 1.21; P = 0.792). Findings suggest the risk of NOD among hypertensive patients is similar between carvedilol and other BB agents (i.e., atenolol, metoprolol succinate, or metoprolol tartrate). The use of administrative claims data and relatively short follow-up period may limit the generalizability of results.

  12. Calcium Channel Blocker Use and Risk of Prostate Cancer by TMPRSS2:ERG Gene Fusion Status.

    Science.gov (United States)

    Geybels, Milan S; McCloskey, Karen D; Mills, Ian G; Stanford, Janet L

    2017-02-01

    Calcium channel blockers (CCBs) may affect prostate cancer (PCa) growth by various mechanisms including those related to androgens. The fusion of the androgen-regulated gene TMPRSS2 and the oncogene ERG (TMPRSS2:ERG or T2E) is common in PCa, and prostate tumors that harbor the gene fusion are believed to represent a distinct disease subtype. We studied the association of CCB use with the risk of PCa, and molecular subtypes of PCa defined by T2E status. Participants were residents of King County, Washington, recruited for population-based case-control studies (1993-1996 or 2002-2005). Tumor T2E status was determined by fluorescence in situ hybridization using tumor tissue specimens from radical prostatectomy. Detailed information on use of CCBs and other variables was obtained through in-person interviews. Binomial and polytomous logistic regression were used to generate odds ratios (ORs) and 95% confidence intervals (CIs). The study included 1,747 PCa patients and 1,635 age-matched controls. A subset of 563 patients treated with radical prostatectomy had T2E status determined, of which 295 were T2E positive (52%). Use of CCBs (ever vs. never) was not associated with overall PCa risk. However, among European-American men, users had a reduced risk of higher-grade PCa (Gleason scores ≥7: adjusted OR = 0.64; 95% CI: 0.44-0.95). Further, use of CCBs was associated with a reduced risk of T2E positive PCa (adjusted OR = 0.38; 95% CI: 0.19-0.78), but was not associated with T2E negative PCa. This study found suggestive evidence that use of CCBs is associated with reduced relative risks for higher Gleason score and T2E positive PCa. Future studies of PCa etiology should consider etiologic heterogeneity as PCa subtypes may develop through different causal pathways. Prostate 77:282-290, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Photolytic degradation of the β-blocker nebivolol in aqueous solution.

    Science.gov (United States)

    Salma, Alaa; Lutze, Holger V; Schmidt, Torsten C; Tuerk, Jochen

    2017-06-01

    Nebivolol (NEB) is one of the top-sold prescription drugs belonging to the third generation of beta-blockers. However, so far, occurrence data in the environment are lacking. Within this study NEB has been found for the first time in effluent samples of wastewater treatment plants in Germany with an average concentration of 13 ng L -1 . Its photodegradation behavior in the environment and in technical processes is largely unknown. To fill this gap, three different UV treatment procedures (UV-C at 254 nm, UV-B at 312 nm and UV-A at 365 nm) were investigated in three different matrices: pure water, pure water in presence of the hydroxyl radical (OH) scavenger tert.-butanol and real wastewater. No elimination was observed during UV-A treatment. In contrast, NEB degradation during UV-B and UV-C treatment followed pseudo first order reaction kinetics, with highest removal rate during UV-C treatment in pure water (k = 7.8 × 10 -4  s -1 ). The rate constant for UV-C irradiation decreased to 2.9 × 10 -4  s -1 in the presence of the OH scavenger and in the presence of the wastewater matrix. The rate constant for the UV-B lamp was 4.4 × 10 -4  s -1 , Three transformation products were identified after UV-B and UV-C photolytic degradation using high resolution mass spectrometry. The main photoreaction is the substitution of the fluorine atoms of NEB by hydroxyl groups. A photolytic cleavage of the CF bond can be excluded as the high bond dissociation energy of aromatic CF bonds (525 kJ mol -1 ), exceeds the energy of electromagnetic radiation applied in the present study (≥254 nm, i.e., max. 471 kJ E -1 ). The quantum yields for NEB degradation for the UV-C lamp achieved in pure water, the OH scavenged system and wastewater matrix were Φ deg  = 0.53, 0.19 and 0.22, respectively. For UV-B Φ deg was 0.023 ± 0.003, noticeable differences in quantum yield were not found. The photooxidation involves reactive oxygen species such as superoxide and

  14. Use of calcium channel blockers in cardiovascular risk reduction: issues in Latin America.

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    Alcocer, Luis; Bendersky, Mario; Acosta, Julio; Urina-Triana, Miguel

    2010-01-01

    Cardiovascular disease (CVD) is a continuum that begins with the presence of several risk factors for CVD, including smoking, hypertension, obesity, diabetes mellitus, and high levels of cholesterol, and if unaddressed can result in premature death, ischemic heart disease, stroke, congestive heart failure, and end-stage renal disease. Hypertension is associated with a significant increase in cardiovascular (CV) morbidity and mortality, raising the risk of stroke, myocardial infarction, heart failure, kidney disease, and peripheral arterial disease. In Latin America, the prevalence of hypertension and other CV risk factors has become similar to that seen in more developed countries, increasing the proportion of the population at high risk for CVD and congestive heart failure; however, it is hypertension that is a key driving force behind CV risk in Latin America. Despite the existence of a wide range of antihypertensive agents, BP control and reductions in CV risk remain poor in Latin America and in Hispanics living in the US. Ethnic differences in treatment rates and disease awareness have been well documented. Studies have shown that calcium channel blockers (CCBs; calcium channel antagonists) are at least as effective in reducing BP and improving the CV risk profile as other classes of antihypertensive agents when administered as monotherapy. CCBs have also been shown to be effective when administered as part of combination therapy in both low- and high-risk hypertensive patients, suggesting that CCBs can easily be combined with other antihypertensive classes in order to achieve BP control and CV risk reduction. In patients with hypertension, coronary artery disease, and high cholesterol, CCBs have been associated with beneficial effects on a range of other aspects of the CV continuum, including the vasculature, coronary calcification, and progression of atherosclerosis. CCBs have also been shown to preserve renal function. Unlike diuretics and beta

  15. Parathyroid hormone levels, calcium-channel blockers, and the dyslipidemia of nondiabetic hemodialysis patients.

    Science.gov (United States)

    Zanos, S; Mitsopoulos, E; Sakellariou, G

    2005-01-01

    Experimental studies have shown that increased levels of parathyroid hormone (PTH) in uremia may cause elevation of intracellular calcium, predisposing to insulin resistance and lipid metabolism abnormalities. Administration of calcium-channel blockers (CCBs) in these models protects against the development of lipid profile abnormalities. This study evaluates the combined effect of intact PTH (iPTH) levels and administration of CCB on the lipid profiles of nondiabetic hemodialysis patients. One hundred and eight non-diabetic hemodialysis patients were studied for 6 months. The population was divided into four groups, according to iPTH levels and administration of CCB: (A) iPTH300 pg/mL without administration of CCB (n=43), (C) iPTH300 pg/mL with CCB administration (n=30). Serum concentrations of total cholesterol, high-density lipoprotein (HDL), triglycerides, and albumin were measured on a monthly basis. All results are shown as mean SE. Total cholesterol values (in mg/ dL) were for group (A) 186 +/- 4, for group (B) 205 +/- 3, for group (C) 200 +/- 3, and for group (D) 203 +/- 4 [p NS between (C) and (D), p<.05 for all other comparisons]. Triglycerides values (in mg/dL) were for group (A) 171 +/- 9, for group (B) 199 +/- 6, for group (C) 190 +/- 6, and for group (D) 191 +/- 9 (p NS for all comparisons). HDL values (in mg/dL) were for group (A) 43.8 +/- 1, for group (B) 35.8 +/- 1, for group (C) 38.3 +/- 0.7, and for group (D) 37.2 +/- 0.7 mg/dL [p NS between (C) and (D), p<.001 for all other comparisons]. Low-density lipoprotein values (in mg/dL) were for group (A) 107.6 +/- 4.4, for group (B) 149.3 +/- 2.5, for group (C) 131.2 +/- 2.9, and for group (D) 126.8 +/- 4.1 [p NS between (C) and (D), p<.001 for all other comparisons]. Atherogenic index values, calculated as [triglycerides/HDL] ratio, were for group (A) 4.6 +/- 0.04 , for group (B) 6.2 +/- 0.04, for group (C) 4.9 +/- 0.03, and for group (D) 5.9 +/- 0.03 [p NS between (C) and (D), p<.004 for all other

  16. WHY BETA-BLOCKERS ARE NOT PRESCRIBED TO PATIENTS WITH HEART FAILURE AND HOW TO IMPROVE IT?

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    S. N. Tereshchenko

    2010-01-01

    Full Text Available Aim. To determine indications for differential prescription of beta-blockers in patients with chronic heart failure (CHF and to study efficacy and safety of beta-blockers therapy.Material and Methods. Patients (n=90; 55.6% of men; aged 64.7±1.9 y.o. with CHF class 3-4 NYHA of ischemic and non-ischemic etiology with inadequate treatment with beta-blockers were included in the study. Patients were randomized into 3 groups depending on received beta-blocker: group 1 (n=30 — bisoprolol, group 2 (n=30 — carvedilol, group 3 (n=30 — nebivolol. Study duration was 6 months. Clinical examination (physical, laboratory and instrumental tests and assessment of the adverse events was performed at baseline and after 6 months. Multiple regression analysis was performed to determine the probability of efficiency achievement by using different parameters (target heart rate, mortality, side effects, hospitalization, 6-minute walk test, left ventricle ejection fraction (LV EF, glomerular filtration rate.Results. Significant increase in LV EF was found: in group 1 from 32.4±6.1 to 47.2±4.1% (p=0.049; in group 2 from 31.3±8.4 to 46.5±4.2% (p=0.047; in group 3 from 30.3±6.9 to 46.8±4.0% (p=0.043. Class NYHA decreased in group 1 from 3.5±0.5 to 2.3±0.3 (p=0.044; in group 2 from 3.4±0.6 to 2.1±0.2 (p=0.045 and in group 3 from 3.6±0.4 to 2.4±0.4 (p=0.038. The hospitalization rate due to heart failure decompensation was 16.7, 16.7 and 13.3%, respectively. Mortality in groups during 6 months was 6.7, 0.0 and 3.3%, respectively. The efficacy of CHF therapy with betablockers depended on comorbidity and demographic characteristics. The highest refractoriness to CHF therapy was in patients with chronic kidney failure, atrial fibrillation and anemia (odds efficiency was 2.2, 2.9 and 3.1%, respectively. Bisoprolol was the most effective beta-blocker for the CHF patients treatment according to the majority of dependent variables in multiple regression analysis

  17. Beta-blocker therapy in patients with left ventricular systolic dysfunction and chronic obstructive lung disease in an ambulatory care setting

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    Billups SJ

    2009-12-01

    Full Text Available Objective: To evaluate beta blocker persistence six months after beta-blocker initiation or dose titration in heart failure (HF patients with COPD compared to those without COPD. Secondary objectives included comparison of beta-blocker dose achieved, changes in left ventricular ejection fraction (LVEF and incidence of hospitalizations or emergency department (ED visits during follow-up.Methods: We conducted a matched, retrospective, cohort study including 86 patients with COPD plus concomitant HF (LVEF ≤40% and 137 patients with HF alone. All patients were followed in an outpatient HF clinic. Eligible patients had a documented LVEF ≤40% and were initiated or titrated on a beta-blocker in the HF clinic. Patients were matched based on LVEF (categorized as ≤ 20% or 21-40%, gender, and age (> or ≤70 years. The primary outcome was beta blocker persistence at 6 months. Secondary outcomes were dose achieved, LVEF, and incidence of hospitalizations or ED visits. Results: There were no differences between the COPD and non-COPD groups in beta-blocker persistence at six-month follow-up (94.2% vs. 93.4% respectively, adjusted p=0.842. The proportion of patients who achieved a daily metoprolol dose equivalent of at least 100 mg was similar between the groups (adjusted p=0.188. The percent of patients with at least one ED visit or hospitalization in the six-month post-titration period was substantial but similar between the groups (53.5% and 48.2% for COPD and non-COPD patients, respectively, adjusted p=0.169. Conclusion: Our results support the use of beta-blockers in the population of heart failure patients with COPD and without reactive airway disease.

  18. The use of alpha-1 adrenergic blockers in children with distal ureterolithiasis: a systematic review and meta-analysis

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    F.P. Glina

    2015-12-01

    Full Text Available Introduction: Urinary lithiasis is the main urologic cause of emergency treatment in adult patient. In the past years, the incidence in children population has increased. However, literature about the use of alpha-1 adrenergic blockers in pediatric population with distal ureterolithiasis is still scarce. The drug acts by decreasing ureter contractions, especially in the distal portion, facilitating calculus expulsion. Objective: This review has the objective to evaluate the use of alpha-1 adrenergic blockers as medical expulsive treatment in children with distal ureterolithiasis. Evidence Acquisition: An electronic literature search was performed using the MEDLINE, COCHRANE, and LILACS databases. We further searched manually the references of the primary studies. Searches were concluded on October 4th, 2014. Articles were selected, independently and in pairs, by the respective titles and summaries. Any divergence was resolved by consensus. Evidence Synthesis: Alpha-1 adrenergic antagonists increased the probability of calculus expulsion by 27% (NNT=4. Calculi smaller than 5mm, increased by 33% (NNT=3. Larger than 5mm, increased by 34% (NNT=3. Conclusion: Alpha-1 adrenergic blocker use is related with a greater incidence of expulsion of ureteral calculi, smaller or greater than 5mm, and fewer episodes of pain when compared to ibuprofen. However it is necessary larger samples to enhance the power analysis of the expulsion of ureteral calculi larger than 5mm and the episodes of pain. Patient Summary: This review analyzed the outcome of alpha adrenergic antagonist in children with ureteral calculi. We conclude that it is the best medicine for use, since it helps the expulsion of the stone.

  19. Effect of voltage-gated sodium channels blockers on motility and viability of human sperm in vitro

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    Hammad Ahmad Gakhar

    2018-03-01

    Full Text Available Objective: To test the effect of voltage-gated sodium channels (VGSCs blockers on the motility and viability of human sperm in-vitro and to evaluate the tested compounds as potential contact spermicidal. Methods: Sperm samples were obtained from healthy nonsmoking volunteers of age 25-30 years who had not taken any drug 3 months before and during the course of the study. The effect of VGSCs blockers evaluated from two pharmacological classes including antiarrhythmic (amiodarone, procainamide and disopyramide and antiepileptic (carbamazepine, oxcarbazepine, phenytoin, and lamotrigine drugs. They were tested on the in-vitro motility and viability of human sperm using Computer Assisted Semen Analyzer. Results: All tested drugs except oxcarbazepine showed dose dependent inhibition of total motility with significant reduction (P<0.05 at the maximum concentration of 200 μM when compared with the control. The concentrations of drugs that reduced total sperm motility to 50% of control (half maximal inhibitory concentration were 2.76, 14.16 and 20.29 μM for phenytoin, lamotrigine and carbamazepine, respectively; and 2.53, 5.32 and 0.37 μM for amiodarone, procainamide and disopyramide, respectively. The anti-motility effects were reversible to various degrees. There was statistically insignificant difference in the inhibition of sperm viability among amiodarone, procainamide and disopyramide. Phenytoin demonstrated the most potent spermicidal action. Conclusions: VGSCs blockers have significant adverse effects on in-vitro motility of human spermatozoa. So in-vivo studies are required to determine their potential toxicological effects on human semen quality, which is an important factor regarding fertility. Moreover, these drugs have the potential to be developed into contact spermicidal.

  20. GOLIMUMAB — A NEW TNF α-BLOCKER. THE REVIEW OF THE EFFICACY AND SAFETY EVALUATION RESULTS

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    R. V. Denisova

    2012-01-01

    Full Text Available The article represents the results of efficacy and safety evaluation of the human monoclonal antibodies — golimumab, according to the data of international multicenter randomized double-blind placebo-controlled trials, including patients with active stage of rheumatoid arthritis. It was shown, that golimumab was reliably more effective than placebo both when administered hypodermic and intravenous. The safety profile of golimumab is comparable to that of the other tumor necrosis factor alpha blockers. The review also contains information on the 3d phase of golimumab efficacy and safety research in patients with juvenile idiopathic arthritis.

  1. EXPERIENCE OF USING A NON-SELECTIVE BETA-BLOCKER IN COMPLEX THERAPY OF REPOLARIZATION DISORDERS IN YOUNG ATHLETES

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    A. Yu. Tikhomirov

    2017-01-01

    Full Text Available Purpose. To study the effectiveness of various schemes of correction of repolarization disorder syndrome, including with the use of beta-blockers, in young athletes of the initial training group.Materials and methods. At the first stage, 410 children involved in sports sections were examined. The average age of the examined was 12.22 ± 3.11 years. At the second stage, the athletes (boys of the initial training group were selected from the surveyed contingent, engaged in martial arts. The groups were formed: A – people with violation of myocardial repolarization processes (72 patients, the average age 10,50 ± 0,35 years, the control group – people without changes in an electrocardiogram (33 people, the average age 10.36 ± 0, 62 years old. All underwent an electrocardiographic study at rest and after physical activity on the Innomed HS80GL apparatus with analysis of the main indicators. The vegetative status and the state of adaptation were estimated by Kerdo index and adaptive potential by Baevsky. After the examination, the subgroup A1 (40 people was prescribed metabolic and antioxidant drugs. Additionally, in the subgroup A2 (32 people, a non-selective beta-blocker was included in the treatment regimen. The course of treatment is 10 days. The analysis of indicators was carried out in 10 days and in a month after the initiation treatment. Statistical processing was carried out in the program Statistica.Results. An earlier disappearance of cardialgia was determined in the subgroup A2 (p < 0.05, whereas in the subgroup A1, 5% of patients had complaints not only at the end of the course, but also a month later after the initiation treatment. The more rapid positive dynamics of the electrocardiographic pattern with a more stable result was observed with the prescription of a beta-blocker.Conclusion. It was proved the advisability of prescribing of beta-blockers in the treatment of beginning athletes with violation of myocardial repolarization

  2. Beta-blocker use and risk of symptomatic bradyarrhythmias: a hospital-based case-control study

    Science.gov (United States)

    Lu, Hou Tee; Kam, Jiyen; Nordin, Rusli Bin; Khelae, Surinder Kaur; Wang, Jing Mein; Choy, Chun Ngok; Lee, Chuey Yan

    2016-01-01

    Objective To investigate the risk factors of symptomatic bradyarrhythmias in relation to β-blockers use. Methods A hospital-based case-control study [228 patients: 108 with symptomatic bradyarrhythmias (cases) and 120 controls] was conducted in Sultanah Aminah Hospital, Malaysia between January 2011 and January 2014. Results The mean age was 61.1 ± 13.3 years with a majority of men (68.9%). Cases were likely than control to be older, hypertensive, lower body mass index and concomitant use of rate-controlling drugs (such as digoxin, verapamil, diltiazem, ivabradine or amiodarone). Significantly higher level of serum potassium, urea, creatinine and lower level of estimated glomerular filtration rate (eGFR) were observed among cases as compared to controls. On univariate analysis among patients on β-blockers, older age (crude OR: 1.07; 95% CI: 1.03–1.11, P = 0.000), hypertension (crude OR: 5.6; 95% CI: 1.51–20.72, P = 0.010), lower sodium (crude OR: 0.04; 95% CI: 0.81–0.99, P = 0.036), higher potassium (crude OR: 2.36; 95% CI: 1.31–4.26, P = 0.004) and higher urea (crude OR: 1.23; 95% CI: 1.11–1.38, P = 0.000) were associated with increased risk of symptomatic bradyarrhythmias; eGFR was inversely and significantly associated with symptomatic bradyarrhythmias in both ‘β-blockers’ (crude OR: 0.97; 95% CI: 0.96–0.98, P = 0.000) and ‘non-β-blockers’ (crude OR: 0.99; 95% CI: 0.97–0.99, P = 0.023) arms. However, eGFR was not significantly associated with symptomatic bradyarrhythmias in the final model of both ‘β-blockers’ (adjusted OR: 0.98; 95% CI: 0.96–0.98, P = 0.103) and ‘non-β-blockers’ (adjusted OR: 0.99; 95% CI: 0.97–1.01, P = 0.328) arms. Importantly, older age was a significant predictor of symptomatic bradyarrhythmias in the ‘β-blockers’ as compared to the ‘non-β-blockers’ arms (adjusted OR: 1.09; 95% CI: 1.03–1.15, P = 0.003 vs. adjusted OR: 1.03; 95% CI: 0.98–1.09, P = 0.232, respectively). Conclusion Older

  3. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis

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    Perdigão, João; Couto, Isabel; Portugal, Isabel; Martins, Marta; Amaral, Leonard; Anes, Elsa; Viveiros, Miguel

    2016-01-01

    Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a) in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b) on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction irrespective of their

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

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    Matthew R Weir

    2001-03-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  6. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Machado, Diana; Pires, David; Perdigão, João; Couto, Isabel; Portugal, Isabel; Martins, Marta; Amaral, Leonard; Anes, Elsa; Viveiros, Miguel

    2016-01-01

    Given the ability of M. tuberculosis to survive as an intracellular pathogen and its propensity to develop resistance to the existing antituberculosis drugs, its treatment requires new approaches. Here the antimycobacterial properties of verapamil, thioridazine, chlorpromazine, flupenthixol and haloperidol were investigated against a panel of drug resistant M. tuberculosis strains, both in vitro and on human-infected macrophages. These compounds are efflux inhibitors that share among them the characteristic of being ion channel blockers. In vitro, all compounds exhibited synergistic inhibitory activities when combined with isoniazid and rifampicin, and were able to inhibit active efflux, demonstrating their role as efflux inhibitors. Gene expression analysis showed that M. tuberculosis efflux genes were overexpressed in response to antibiotic exposure, in vitro and within macrophages, irrespective of their resistance pattern. These compounds displayed a rapid and high killing activity against M. tuberculosis, associated with a decrease in intracellular ATP levels demonstrating that the bactericidal action of the ion channel blockers against M. tuberculosis clinical strains is associated with their interference with energy metabolism. The compounds led to a decrease in the intracellular mycobacterial load by increasing phagosome acidification and activating lysosomal hydrolases. The results presented in this study enable us to propose the following mechanism of action for these compounds: a) in the bacteria, the compounds generate a cascade of events involving the inhibition of the respiratory chain complexes and energy production for efflux activity. Indirectly, this reduce the resistance level to antituberculosis drugs potentiating their activity; b) on the host cell, the treatment with the ion channel blockers increases phagosome acidification and induces the expression of phagosomal hydrolases, leading to bacterial growth restriction irrespective of their

  7. Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus – a systematic review and meta-analysis

    Science.gov (United States)

    Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

    2015-01-01

    Aims Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. Methods We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. Results From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l−1 (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l−1 (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI −0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Conclusions Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. PMID:25377481

  8. Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus - a systematic review and meta-analysis.

    Science.gov (United States)

    Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

    2015-05-01

    Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l(-1) (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l(-1) (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI -0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. © 2014 The British Pharmacological Society.

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

    Directory of Open Access Journals (Sweden)

    Matej Samoš

    2016-01-01

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

  10. Efficacy and safety of tumor necrosis factor-α blockers for ulcerative colitis: A systematic review and meta-analysis of published randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Yun-Na Song

    2015-03-01

    Full Text Available To evaluate the efficacy and safety of TNF-α blockers for ulcerative colitis. A systematic search for randomized controlled trials (RCTs of TNF-α blockers for treatment of ulcerative colitis (UC were performed in PubMed, Web of Science, Embase and cochrane clinical trial. We estimated Pooled estimates of the odds ratio (OR and relevant 95% confidence interval (CI using fixed effects model or random effects model as appropriate. Heterogeneity, publication bias, and subgroup analyses were conducted. Nine randomized controlled studies met the selection criteria with a total of 2518 patients. Five studies compared Infliximab with placebo. Two studies compared Infliximab to corticosteroids. Two studies compared Adalimumab to placebo. One study compared subcutaneous golimumab to placebo. Short-term response, short-term remission, long-term remission and mucosal healing were better in the TNF-α blocker group than in the control group (p < 0.05. TNF-α blockers decreased the colectomy rate and serious adverse reactions (p < 0.05. The TNF-α blockers were superior to controls in achieving short-term clinical response/remission, long-term remission and mucosal healing and decreased the colectomy rate and serious adverse reactions.

  11. Poly(ethylene glycol as a scaffold for high-affinity open-channel blockers of the mouse nicotinic acetylcholine receptor.

    Directory of Open Access Journals (Sweden)

    Wan-Chen Lin

    Full Text Available High-affinity blockers for an ion channel often have complex molecular structures that are synthetically challenging and/or laborious. Here we show that high-affinity blockers for the mouse nicotinic acetylcholine receptor (AChR can be prepared from a structurally simple material, poly(ethylene glycol (PEG. The PEG-based blockers (PQ1-5, comprised of a flexible octa(ethylene glycol scaffold and two terminal quaternary ammonium groups, exert low- to sub-micromolar affinities for the open AChR pore (measured via single-channel analysis of AChRs expressed in human embryonic kidney cells. PQ1-5 are comparable in pore-binding affinity to the strongest AChR open-channel blockers previously reported, which have complex molecular structures. These results suggest a general approach for designing potent open-channel blockers from a structurally flexible polymer. This design strategy involves simple synthetic procedures and does not require detailed information about the structure of an ion-channel pore.

  12. Point correlation dimension can reveal functional changes caused by gap junction blockers in the 4-aminopyridine in vivo rat epilepsy model

    Energy Technology Data Exchange (ETDEWEB)

    Jardanhazy, Anett [Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged H-6725 (Hungary); Molnar, Mark [Department of Psychophysiology, Institute for Psychology of the Hungarian Academy of Sciences, P.O. Box 398, Budapest H-1394 (Hungary)], E-mail: molnar@cogpsyphy.hu; Jardanhazy, Tamas [Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged H-6725 (Hungary)], E-mail: jt@nepsy.szote.u-szeged.hu

    2009-04-15

    The contribution of gap junction (GJ) blockers to seizure initiation was reexamined by means of an analysis on nonlinear dynamics with point correlation dimension (PD2i) at as well as around the primary focus, and mirror focus in an already active 4-aminopyridine-induced in vivo epilepsy model. From the data base of the ECoGs of anesthetized adult rats treated with quinine, a selective blocker of Cx36, and in combination with an additional broad-spectrum GJ blocker, carbenoxolone, 14 cases of each condition were reexamined with a stationarity insensitive nonlinear PD2i method. The blockade of the Cx36 channels decreased the usual drop of the point correlation dimension at the beginning of the seizures, and this was enhanced by the additional use of the global blocker carbenoxolone. The so-called characteristic DC shift just prior to seizure onset denotes a low dimensional seizure event and the recognizable seizures display very variable, rapidly changing dynamics, as revealed by the PD2i analysis. This nonlinear PD2i analysis demonstrated that the different GJ blockers in the already active epileptic model helped seizure initiation, but exerted inhibitory effects on the seizure onset itself, acting differently on the local components of the network organization generating seizure discharges, possibly changing the coupling strengths and time delays in the GJ-s.

  13. Brookhaven Linac Isotope Producer

    Data.gov (United States)

    Federal Laboratory Consortium — The Brookhaven Linac Isoptope Producer (BLIP)—positioned at the forefront of research into radioisotopes used in cancer treatment and diagnosis—produces commercially...

  14. Producing Against Poverty

    NARCIS (Netherlands)

    Ypeij, Annelou

    2000-01-01

    Producing against Poverty is an anthropological research on micro-entrepreneurs in Lima, Peru. It analyses the way micro-producers accumulate capital. The anthropological approach of the book starts with an analysis of the daily lives of the micro-producers. Its gender approach makes a comparison

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

    Science.gov (United States)

    Ho, Jean K; Nation, Daniel A

    2017-04-26

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

  16. Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model.

    Science.gov (United States)

    Salama, Mohamed; Elhussiny, Mahmoud; Magdy, Alshimaa; Omran, Ahmed G; Alsayed, Aziza; Ashry, Ramy; Mohamed, Wael

    2017-10-27

    Tauopathy comprises a group of disorders caused by abnormal aggregates of tau protein. In these disorders phosphorylated tau protein tends to accumulate inside neuronal cells (soma) instead of the normal axonal distribution of tau. A suggested therapeutic strategy for tauopathy is to induce autophagy to increase the ability to get rid of the unwanted tau aggregates. One of the key controllers of autophagy is mTOR. Blocking mTOR leads to stimulation of autophagy. Recently, unravelling molecular structure of mTOR showed that it is formed of two subunits: mTORC1/C2. So, blocking both subunits of mTOR seems more attractive as it will explore all abilities of mTOR molecule. In the present study, we report using pp242 which is a dual mTORC1/C2 blocker in cellular model of tauopathy using LUHMES cell line. Adding fenazaquin to LUHMES cells induced tauopathy in the form of increased phospho tau aggregates. Moreover, fenazaquin treated cells showed the characteristic somatic redistribution of tau. PP242 use in the present tauopathy model reversed the pathology significantly without observable cellular toxicity for the used dosage of 1000 nM. The present study suggests the possible use of pp242 as a dual mTOR blocker to treat tauopathy.

  17. TNF-α Blocker Effect of Naringenin-Loaded Sericin Microparticles that Are Potentially Useful in the Treatment of Psoriasis

    Directory of Open Access Journals (Sweden)

    Theodora Chlapanidas

    2014-08-01

    Full Text Available This study aims to evaluate the effect of combined use of the racemic flavanone Naringenin (NRG and the protein sericin as TNF-α blockers. Sericin (SMs and (R/S NRG-loaded Sericin (SNRGMs microparticles were prepared by spray-drying, characterized in terms of morphology and particle size distribution, and encapsulation efficiency was determined. Concerning morphology and particle size distribution of microparticles, results indicated that they were not affected by the presence of NRG. The encapsulation efficiency was almost quantitative (93%, thus proving that sericin can be advantageously loaded with (R/S NRG. Biological evaluation of (R/S NRG, SMs and SNRGMs was then performed in lipopolysaccharide (LPS-stimulated human peripheral blood mononuclear cells (hPBMC. SNRGMs resulted cytotoxic at the higher dose used (200 μg/mL and the effect was greater than (R/S NRG alone. Moreover, even if sericin alone was not effective in suppressing LPS-induced serum TNF-α levels, SNRGMs loaded with 9.3% of (R/S NRG were significantly more potent than (R/S NRG alone. In summary, this study provides the proof of concept that sericin-based microspheres loaded with TNF-α-blockers could contribute to the down regulation of the cytokine and represents the starting point for the development of new topical formulations for the treatment of middle-stage psoriasis.

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

    Science.gov (United States)

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

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

  19. Inotropic effects of the K+ channel blocker 3,4-diaminopyridine: differential responses of rat soleus and extensor digitorum longus.

    Science.gov (United States)

    van Lunteren, Erik; Pollarine, Jennifer; Moyer, Michelle

    2006-12-01

    The K+ channel blocker 3,4-diaminopyrindine (DAP) increases diaphragm force, use of which could potentially improve muscle performance during functional neuromuscular stimulation. To determine the extent of hindlimb muscle force augmentation, and delineate whether DAP effects vary in muscles comprised of mainly slow versus fast fibers, rat soleus, extensor digitorum longus (EDL) and diaphragm muscle samples were studied in vitro. DAP increased force of all three muscles, but at high concentrations the force increases were transient and were followed by declines in force below baseline. The maximum DAP-induced twitch force increase was smaller for soleus (38 +/-7%) than both EDL (94+/-12%) (P < 0.05) and diaphragm (93+/-13%) (P < 0.01). During fatigue-inducing 20 Hz stimulation (tested at an intermediate DAP concentration), force of soleus muscle remained significantly elevated by DAP for the entire testing period, force of DAP-treated EDL muscle rapidly declined to values in untreated muscle, and force of DAP-treated diaphragm had an intermediate force-time profile. Muscles varied in extent to which isometric contractile kinetics were altered by DAP. Thus, the K+ channel blocker DAP improves contractile performance of limb muscles, but the profile of improvement is distinct between the soleus and EDL muscles.

  20. Infusion of gliotoxins or a gap junction blocker in the prelimbic cortex increases alcohol preference in Wistar rats.

    Science.gov (United States)

    Miguel-Hidalgo, J; Shoyama, Y; Wanzo, V

    2009-07-01

    Postmortem research has revealed that there is a lower density of glial cells in regions of the prefrontal cortex (PFC) of uncomplicated alcoholics when compared with control subjects. Impairment of astrocyte function in the PFC may contribute to malfunction in circuits involved in emotion- and reward-related subcortical centers, heavily connected with the PFC and directly involved in the pathophysiology of addictive behaviours. The hypothesis was tested that infusion of gliotoxins known to injure astrocytes or of a gap junction blocker into the prelimbic area of the rat PFC results in increased preference for ethanol in rats exposed to free choice between water and 10% ethanol. Fluorocitric acid, L-alpha-aminoadipic acid (AAD) or the gap junction blocker 18-alpha-glycyrrhetinic acid (AGA) were bilaterally infused once into the rat prelimbic cortex and alcohol preference (ratio of 10% ethanol consumed to total liquid ingested) was measured before and after infusion. Infusion of AAD or AGA dissolved in their vehicles, but not of their vehicles alone, resulted in significant transient increase of preference for 10% ethanol. The present data suggest that impaired integrity of glial cells or the gap junctional communication between them in the rat PFC may contribute to changes in ethanol preference.

  1. No Association Between Calcium Channel Blockers and Survival in Patients with Cancer: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Sun, Hong; Zhuang, Rong-Yuan; Li, Tao; Zheng, Yuan-Ting; Cai, Wei-Min

    2016-01-01

    Any association between calcium channel blockers (CCBs) and survival in cancer patients remains unclear and the results of related studies are conflicting. The objective of the study was to investigate the association between calcium channel blocker (CCB) use and survival in cancer patients. We searched PubMed, EMBASE, Web of Science and Cochrane Library for studies published before January 2016 with terms related to CCBs and survival in cancer patients. The information was reviewed and extracted by two evaluators independently. Data from publications were extracted and used to calculate hazard ratios (HRs) for overall survival (OS). Statistical analysis was performed by using Review Manager 5.3. There were 11 studies included in our meta-analysis. Analysis of all showed that CCBs use was not associated with survival in cancer patients (HR=1.07; 95% CI: 0.91-1.25; P=0.42). No association between CCB use and overall survival in cancer patients existed, whether in Asian (HR=1.18, 95% CI: 0.72-1.93; P=0.52) or Caucasian populations (HR=1.03, 95% CI: 0.89-1.20; P=0.66). There is no evidence that CCB use is associated with a better or worse survival in cancer patients.

  2. TNF-α blocker effect of naringenin-loaded sericin microparticles that are potentially useful in the treatment of psoriasis.

    Science.gov (United States)

    Chlapanidas, Theodora; Perteghella, Sara; Leoni, Flavio; Faragò, Silvio; Marazzi, Mario; Rossi, Daniela; Martino, Emanuela; Gaggeri, Raffaella; Collina, Simona

    2014-08-06

    This study aims to evaluate the effect of combined use of the racemic flavanone Naringenin (NRG) and the protein sericin as TNF-α blockers. Sericin (SMs) and (R/S) NRG-loaded Sericin (SNRGMs) microparticles were prepared by spray-drying, characterized in terms of morphology and particle size distribution, and encapsulation efficiency was determined. Concerning morphology and particle size distribution of microparticles, results indicated that they were not affected by the presence of NRG. The encapsulation efficiency was almost quantitative (93%), thus proving that sericin can be advantageously loaded with (R/S) NRG. Biological evaluation of (R/S) NRG, SMs and SNRGMs was then performed in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (hPBMC). SNRGMs resulted cytotoxic at the higher dose used (200 μg/mL) and the effect was greater than (R/S) NRG alone. Moreover, even if sericin alone was not effective in suppressing LPS-induced serum TNF-α levels, SNRGMs loaded with 9.3% of (R/S) NRG were significantly more potent than (R/S) NRG alone. In summary, this study provides the proof of concept that sericin-based microspheres loaded with TNF-α-blockers could contribute to the down regulation of the cytokine and represents the starting point for the development of new topical formulations for the treatment of middle-stage psoriasis.

  3. A novel K+ competitive acid blocker, YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: randomised clinical study in healthy volunteers.

    Science.gov (United States)

    Yi, S; Lee, H; Jang, S B; Byun, H M; Yoon, S H; Cho, J-Y; Jang, I-J; Yu, K-S

    2017-08-01

    YH4808, a K + -competitive acid blocker, is under clinical development for the treatment of acid-related disorders, such as gastroesophageal reflux disease. To determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH4808, compared to placebo and esomeprazole. This double-blind, randomised, placebo- and active comparator (esomeprazole)-controlled study was conducted with 123 healthy male volunteers. We evaluated YH4808 (30-800 mg) properties, administered in single (N=55) and multiple (N=24) oral doses, and recorded the effects on 24-hour intragastric acidity. Results were compared to placebo (N=20) and esomeprazole 40 mg (N=24). Plasma YH4808 exposure increased dose-proportionally and declined in a multi-phasic manner. YH4808 ≥200 mg/d maintained intragastric acidity at pH >4 for longer times than esomeprazole during both day and night (%Time at pH >4: >70% vs 58% of a 24-hour period, respectively; and >50% vs 33% of a 9-hour night respectively). A twice-daily regimen of YH4808 more effectively controlled intragastric pH at night than a once-daily regimen. In evaluating the mean areas under the intragastric pH-time curves in 15-minute intervals for 2 hours after dosing, we found that YH4808 had a faster onset than esomeprazole. Moreover, unlike esomeprazole, YH4808 PK and PD were not significantly affected by the CYP2C19 genotype of the subjects. YH4808 was well-tolerated at all doses administered. This study showed that YH4808 produced a rapid, sustained suppression of gastric secretion with good tolerability. The results at YH4808 ≥200 mg/d provide a rationale for further clinical investigations in populations with acid-related diseases. © 2017 John Wiley & Sons Ltd.

  4. Trans-channel interactions in batrachotoxin-modified rat skeletal muscle sodium channels: kinetic analysis of mutual inhibition between mu-conotoxin GIIIA derivatives and amine blockers.

    Science.gov (United States)

    Ma, Quanli; Pavlov, Evgeny; Britvina, Tatiana; Zamponi, Gerald W; French, Robert J

    2008-11-01

    R13X derivatives of mu-conotoxin GIIIA bind externally to single sodium channels and block current incompletely with mean "blocked" durations of several seconds. We studied interactions between two classes of blockers (mu-conotoxins and amines) by steady state, kinetic analysis of block of BTX-modified Na channels in planar bilayers. The amines cause all-or-none block at a site internal to the selectivity filter. TPrA and DEA block single Na channels with very different kinetics. TPrA induces discrete, all-or-none, blocked events (mean blocked durations, approximately 100 ms), whereas DEA produces a concentration-dependent reduction of the apparent single channel amplitude ("fast" block). These distinct modes of action allow simultaneous evaluation of block by TPrA and DEA, showing a classical, competitive interaction between them. The apparent affinity of TPrA decreases with increasing [DEA], based on a decrease in the association rate for TPrA. When an R13X mu-conotoxin derivative and one of the amines are applied simultaneously on opposite sides of the membrane, a mutually inhibitory interaction is observed. Dissociation constants, at +50 mV, for TPrA ( approximately 4 mM) and DEA ( approximately 30 mM) increase by approximately 20%-50% when R13E (nominal net charge, +4) or R13Q (+5) is bound. Analysis of the slow blocking kinetics for the two toxin derivatives showed comparable decreases in affinity of the mu-conotoxins in the presence of an amine. Although this mutual inhibition seems to be qualitatively consistent with an electrostatic interaction across the selectivity filter, quantitative considerations raise questions about the mechanistic details of the interaction.

  5. Experimental demonstration of a real-time high-throughput digital DC blocker for compensating ADC imperfections in optical fast-OFDM receivers.

    Science.gov (United States)

    Zhang, Lu; Ouyang, Xing; Shao, Xiaopeng; Zhao, Jian

    2016-06-27

    Performance degradation induced by the DC components at the output of real-time analogue-to-digital converter (ADC) is experimentally investigated for optical fast-OFDM receiver. To compensate this degradation, register transfer level (RTL) circuits for real-time digital DC blocker with 20GS/s throughput are proposed and implemented in field programmable gate array (FPGA). The performance of the proposed real-time digital DC blocker is experimentally investigated in a 15Gb/s optical fast-OFDM system with intensity modulation and direct detection over 40 km standard single-mode fibre. The results show that the fixed-point DC blocker has negligible performance penalty compared to the offline floating point one, and can overcome the error floor of the fast OFDM receiver caused by the DC components from the real-time ADC output.

  6. Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995-2002

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Abildstrom, Steen Z; Rasmussen, Jeppe Nørgaard

    2005-01-01

    pharmacies within 30 d from discharge was obtained from the National Patient Registry and the Danish Registry of Medicinal Product Statistics. RESULTS: Beta-blocker use increased from 38.1% of patients in 1995 to 67.9% in 2002 (OR = 3.85, CI: 3.58-4.13). Women, elderly patients and patients taking loop-diuretics...... and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR = 1.86, CI: 1.72-2.01). Women, patients aged or = 80 years and patients not taking loop-diuretics...... received ACE inhibitors less frequently, but patients not taking loop-diuretics had the greatest increase. CONCLUSIONS: Beta-blocker use increased markedly post-AMI from 1995 to 2002, whereas ACE inhibitor use increased modestly. The results suggested undertreatment of women, elderly patients and people...

  7. Is Shock Index a Valid Predictor of Mortality in Emergency Department Patients With Hypertension, Diabetes, High Age, or Receipt of β- or Calcium Channel Blockers?

    DEFF Research Database (Denmark)

    Kristensen, Anders K B; Holler, Jon G; Hallas, Jesper

    2016-01-01

    differences within subgroups. The adjusted analyses showed similar ORs. CONCLUSION: Shock index is independently associated with 30-day mortality in a broad population of ED patients. Old age, hypertension, and β- or calcium channel blockers weaken this association. However, a shock index greater than......STUDY OBJECTIVE: Shock index is a widely reported tool to identify patients at risk for circulatory collapse. We hypothesize that old age, diabetes, hypertension, and β- or calcium channel blockers weaken the association between shock index and mortality. METHODS: This was a cohort study of all...... first-time emergency department (ED) visits between 1995 and 2011 (n=111,019). We examined whether age 65 years or older, diabetes, hypertension, and use of β- or calcium channel blockers modified the association between shock index and 30-day mortality. RESULTS: The 30-day mortality was 3.0%. For all...

  8. Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Mookerjee, Rajeshwar P; Pavesi, Marco; Thomsen, Karen Louise

    2016-01-01

    BACKGROUND & AIMS: Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF) is char......BACKGROUND & AIMS: Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF...

  9. PITX2 Modulates Atrial Membrane Potential and the Antiarrhythmic Effects of Sodium-Channel Blockers.

    Science.gov (United States)

    Syeda, Fahima; Holmes, Andrew P; Yu, Ting Y; Tull, Samantha; Kuhlmann, Stefan Michael; Pavlovic, Davor; Betney, Daniel; Riley, Genna; Kucera, Jan P; Jousset, Florian; de Groot, Joris R; Rohr, Stephan; Brown, Nigel A; Fabritz, Larissa; Kirchhof, Paulus

    2016-10-25

    Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs. LA PITX2 messenger ribonucleic acid (mRNA) levels were measured in 95 patients undergoing thoracoscopic AF ablation. The effects of flecainide, a sodium (Na + )-channel blocker, and d,l-sotalol, a potassium channel blocker, were studied in littermate mice with normal and reduced Pitx2c mRNA by electrophysiological study, optical mapping, and patch clamp studies. PITX2-dependent mechanisms of antiarrhythmic drug action were studied in human embryonic kidney (HEK) cells expressing human Na channels and by modeling human action potentials. Flecainide 1 μmol/l was more effective in suppressing atrial arrhythmias in atria with reduced Pitx2c mRNA levels (Pitx2c +/- ). Resting membrane potential was more depolarized in Pitx2c +/- atria, and TWIK-related acid-sensitive K + channel 2 (TASK-2) gene and protein expression were decreased. This resulted in enhanced post-repolarization refractoriness and more effective Na-channel inhibition. Defined holding potentials eliminated differences in flecainide's effects between wild-type and Pitx2c +/- atrial cardiomyocytes. More positive holding potentials replicated the increased effectiveness of flecainide in blocking human Na v 1.5 channels in HEK293 cells. Computer modeling reproduced an enhanced effectiveness of Na-channel block when resting membrane potential was slightly depolarized. PITX2 mRNA modulates atrial resting membrane potential and thereby alters the effectiveness of Na

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

    Science.gov (United States)

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

    2013-12-01

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

  11. Biologically produced sulfur

    NARCIS (Netherlands)

    Kleinjan, W.E.; Keizer, de A.; Janssen, A.J.H.

    2003-01-01

    Sulfur compound oxidizing bacteria produce sulfur as an intermediate in the oxidation of hydrogen sulfide to sulfate. Sulfur produced by these microorganisms can be stored in sulfur globules, located either inside or outside the cell. Excreted sulfur globules are colloidal particles which are

  12. Consumers and Producers

    NARCIS (Netherlands)

    E. Maira (Elisa)

    2018-01-01

    markdownabstractIn the last few decades, advances in information and communication technology have dramatically changed the way consumers and producers interact in the marketplace. The Internet and social media have torn down the information barrier between producers and consumers, leading to

  13. Fungi producing significant mycotoxins.

    Science.gov (United States)

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  15. Dissection of the Mechanical Impedance Components of the Outer Hair Cell Using a Chloride-Channel Blocker

    Science.gov (United States)

    Harasztosi, Csaba; Gummer, Anthony W.

    2011-11-01

    The voltage-dependent chloride-channel blocker anthracene-9-carboxylic acid (9AC) has been found to reduce the imaginary but not the real part of the mechanical impedance of the organ of Corti, suggesting that the effective stiffness of outer hair cells (OHCs) is reduced by 9AC. To examine whether 9AC interacts directly with the motor protein prestin to reduce the membrane component of the impedance, the patch-clamp technique in whole-cell configuration was used to measure the nonlinear capacitance (NLC) of isolated OHCs and, as control, prestin-transfected human embryonic kidney 293 (HEK293) cells. Extracellular application of 9AC significantly reduced the NLC of both OHCs and HEK293 cells. Intracellular 9AC did not influence the blocking effect of the extracellular applied drug. These results suggest that 9AC interacts directly with prestin, reducing the effective stiffness of the motor, and that the interaction is extracellular.

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

    Science.gov (United States)

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

    2015-02-01

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

  17. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors.

    Science.gov (United States)

    Rubio-Guerra, Alberto F; Castro-Serna, David; Barrera, Cesar I Elizalde; Ramos-Brizuela, Luz M

    2009-01-01

    Recent guidelines for the management of hypertension recommend target blood pressures hypertensive patients, or hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS) are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension - European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  19. Calcium-channel blockers do not alter the clinical efficacy of clopidogrel after myocardial infarction: a nationwide cohort study

    DEFF Research Database (Denmark)

    Olesen, Jonas B; Gislason, Gunnar H; Charlot, Mette G

    2011-01-01

    Objectives The purpose of this study was to determine the risk of adverse cardiovascular events associated with concomitant use of clopidogrel and calcium-channel blockers (CCBs) in patients with myocardial infarction (MI). Background CCBs inhibit a variety of cytochrome P-450 enzymes, some...... patients treated and not treated with clopidogrel, with a hazard ratio of 1.15 (95% confidence interval [CI]: 1.07 to 1.24) and 1.05 (95% CI: 1.01 to 1.11), respectively. The increased risk was independent of clopidogrel use; the hazard rate ratio was 1.08 (95% CI: 0.99 to 1.18). Analyses of all additional...... adverse end points and propensity score–matched models provided similar results. Conclusions The clinical efficacy of clopidogrel in patients with a recent MI is not modified by concomitant CCB treatment. This potential drug interaction is unlikely to have clinical significance....

  20. Nonspecific effects of the gap junction blocker mefloquine on fast hippocampal network oscillations in the adult rat in vitro.

    Science.gov (United States)

    Behrens, C J; Ul Haq, R; Liotta, A; Anderson, M L; Heinemann, U

    2011-09-29

    It has been suggested that gap junctions are involved in the synchronization during high frequency oscillations as observed during sharp wave-ripple complexes (SPW-Rs) and during recurrent epileptiform discharges (REDs). Ripple oscillations during SPW-Rs, possibly involved in memory replay and memory consolidation, reach frequencies of up to 200 Hz while ripple oscillations during REDs display frequencies up to 500 Hz. These fast oscillations may be synchronized by intercellular interactions through gap junctions. In area CA3, connexin 36 (Cx36) proteins are present and potentially sensitive to mefloquine. Here, we used hippocampal slices of adult rats to investigate the effects of mefloquine, which blocks Cx36, Cx43 and Cx50 gap junctions on both SPW-Rs and REDs. SPW-Rs were induced by high frequency stimulation in the CA3 region while REDs were recorded in the presence of the GABA(A) receptor blocker bicuculline (5 μM). Both, SPW-Rs and REDs were blocked by the gap junction blocker carbenoxolone. Mefloquine (50 μM), which did not affect stimulus-induced responses in area CA3, neither changed SPW-Rs nor superimposed ripple oscillations. During REDs, 25 and 50 μM mefloquine exerted only minor effects on the expression of REDs but significantly reduced the amplitude of superimposed ripples by ∼17 and ∼54%, respectively. Intracellular recordings of CA3 pyramidal cells revealed that mefloquine did not change their resting membrane potential and input resistance but significantly increased the afterhyperpolarization following evoked action potentials (APs) resulting in reduced probability of AP firing during depolarizing current injection. Similarly, mefloquine caused a reduction in AP generation during REDs. Together, our data suggest that mefloquine depressed RED-related ripple oscillations by reducing high frequency discharges and not necessarily by blocking electrical coupling. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Effects of the topically applied calcium-channel blocker flunarizine on intraocular pressure in clinically normal dogs.

    Science.gov (United States)

    Greller, Andrew L; Hoffman, Allison R; Liu, Chengcheng; Ying, Gui-shuang; Vudathala, Daljit K; Acland, Gregory M; Komáromy, András M

    2008-02-01

    To determine effects of the topically applied calcium-channel blocker flunarizine on intraocular pressure (IOP) in clinically normal dogs. 20 dogs. Baseline diurnal IOPs were determined by use of a rebound tonometer on 2 consecutive days. Subsequently, 1 randomly chosen eye of each dog was treated topically twice daily for 5 days with 0.5% flunarizine. During this treatment period, diurnal IOPs were measured. In addition, pupillary diameter and mean arterial blood pressure (MAP) were evaluated. Serum flunarizine concentrations were measured on treatment day 5. Intraday fluctuation of IOP was analyzed by use of an ANOVA for repeated measures and a trend test. Changes in IOP from baseline values were assessed and compared with IOPs for the days of treatment. Values were also compared between treated and untreated eyes. A significant intraday fluctuation in baseline IOP was detected, which was highest in the morning (mean +/- SE, 15.8 +/- 0.63 mm Hg) and lowest at night (12.9 +/- 0.61 mm Hg). After 2 days of treatment, there was a significant decrease in IOP from baseline values in treated (0.93 +/- 0.35 mm Hg) and untreated (0.95 +/- 0.34 mm Hg) eyes. There was no significant treatment effect on pupillary diameter or MAP. Flunarizine was detected in serum samples of all dogs (mean +/- SD, 3.89 +/- 6.36 microg/L). Topically applied flunarizine decreased IOP in dogs after 2 days of twice-daily application. This calcium-channel blocker could be effective in the treatment of dogs with glaucoma.

  2. Beneficial effects of beta-blockers on left ventricular function and cellular energy reserve in patients with heart failure.

    Science.gov (United States)

    Spoladore, Roberto; Fragasso, Gabriele; Perseghin, Gianluca; De Cobelli, Francesco; Esposito, Antonio; Maranta, Francesco; Calori, Giliola; Locatelli, Massimo; Lattuada, Guido; Scifo, Paola; Del Maschio, Alessandro; Margonato, Alberto

    2013-08-01

    Beta-blockers have been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy (31P-MRS), the effects of beta-blockers on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure. Ten heart failure patients on full medical therapy were beta-blocked by either carvedilol or bisoprolol. Before and after 3 months of treatment, exercise testing, 2D echocardiography, MRS, New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate-pressure product and exercise metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. After beta-blockade, NYHA class decreased (from 2.2 ± 0.54 to 1.9 ± 0.52, P = 0.05), whereas EF (from 33 ± 7 to 44 ± 6%, P = 0.0009) and METS (from 6.74 ± 2.12 to 8.03 ± 2.39, P = 0.01) increased. Accordingly, the mean cardiac PCr/ATP ratio increased by 33% (from 1.48 ± 0.22 to 1.81 ± 0.48, P = 0.03). Beta-blockade-induced symptomatic and functional improvement in patients with heart failure is associated to increased PCr/ATP ratio, indicating preservation of myocardial high-energy phosphate levels. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.

  3. Perioperative management of patients treated with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: a quality improvement audit.

    Science.gov (United States)

    Vijay, A; Grover, A; Coulson, T G; Myles, P S

    2016-05-01

    Previous studies have shown that patients continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers on the day of surgery are more likely to have significant intraoperative hypotension, higher rates of postoperative acute kidney injury, and lower incidences of postoperative atrial fibrillation. However, many of these studies were prone to bias and confounding, and questions remain over the validity of these outcomes. This observational, before-and-after quality improvement audit aimed to assess the effect of withholding these medications on the morning of surgery. We recruited 323 participants, with 83 (26%) having their preoperative angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) withheld on the day of surgery. There were only very small Spearman rank-order correlations between time since last dose of these medications (rho -0.12, P=0.057) and intraoperative and recovery room intravenous fluid administration (rho -0.11, P=0.042). There was no statistically significant difference between the continued or withheld groups in vasopressor (metaraminol use 3.5 [1.5-8.3] mg versus 3.5 [1.5-8.5] mg, P=0.67) or intravenous fluid administration (1000 ml [800-1500] ml versus 1000 [800-1500] ml, P=0.096), nor rates of postoperative acute kidney injury (13% vs 18%, P=0.25) or atrial fibrillation (15% versus 18%, P=0.71). This audit found no significant differences in measured outcomes between the continued or withheld ACEi/ARB groups. This finding should be interpreted with caution due to the possibility of confounding and an insufficient sample size. However, as the finding is in contrast to many previous studies, future prospective randomised clinical trials are required to answer this important question.

  4. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

    Directory of Open Access Journals (Sweden)

    Alberto F Rubio-Guerra

    2009-11-01

    Full Text Available Alberto F Rubio-Guerra1, David Castro-Serna2, Cesar I Elizalde Barrera2, Luz M Ramos-Brizuela21Metabolic and Research Clinic, 2Internal Medicine Department, Hospital General de Ticomán SS DF, MéxicoAbstract: Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.Keywords: hypertension, calcium channel blockers, renin-angiotensin-aldosterone system inhibitors, fixed-dose combination, adherence

  5. Cross-bridge blocker BTS permits direct measurement of SR Ca2+ pump ATP utilization in toadfish swimbladder muscle fibers.

    Science.gov (United States)

    Young, Iain S; Harwood, Claire L; Rome, Lawrence C

    2003-10-01

    Because the major processes involved in muscle contraction require rapid utilization of ATP, measurement of ATP utilization can provide important insights into the mechanisms of contraction. It is necessary, however, to differentiate between the contribution made by cross-bridges and that of the sarcoplasmic reticulum (SR) Ca2+ pumps. Specific and potent SR Ca2+ pump blockers have been used in skinned fibers to permit direct measurement of cross-bridge ATP utilization. Up to now, there was no analogous cross-bridge blocker. Recently, N-benzyl-p-toluene sulfonamide (BTS) was found to suppress force generation at micromolar concentrations. We tested whether BTS could be used to block cross-bridge ATP utilization, thereby permitting direct measurement of SR Ca2+ pump ATP utilization in saponin-skinned fibers. At 25 microM, BTS virtually eliminates force and cross-bridge ATP utilization (both BTS. At 25 microM, BTS had no effect on SR pump ATP utilization. Hence, we used BTS to make some of the first direct measurements of ATP utilization of intact SR over a physiological range of [Ca2+]at 15 degrees C. Curve fits to SR Ca2+ pump ATP utilization vs. pCa indicate that they have much lower Hill coefficients (1.49) than that describing cross-bridge force generation vs. pCa (approximately 5). Furthermore, we found that BTS also effectively eliminates force generation in bundles of intact swimbladder muscle, suggesting that it will be an important tool for studying integrated SR function during normal motor behavior.

  6. CYP2D6 Genetic Variation and Beta-Blocker Maintenance Dose in Patients with Heart Failure.

    Science.gov (United States)

    Luzum, Jasmine A; Sweet, Kevin M; Binkley, Philip F; Schmidlen, Tara J; Jarvis, Joseph P; Christman, Michael F; Sadee, Wolfgang; Kitzmiller, Joseph P

    2017-08-01

    This study examined whether a CYP2D6 polymorphism (CYP2D6*4) was related to beta-blocker maintenance dose in patients with heart failure. Logistic regression modeling was utilized in a retrospective chart-review analysis of heart-failure patients (60% Male, 90% of European descent) to assess whether CYP2D6*4 (non-functional CYP2D6 allele present in 1 of 5 individuals of European descent) is associated with maintenance dose of carvedilol (n = 65) or metoprolol (n = 33). CYP2D6*4 was associated with lower maintenance dose of metoprolol (OR 0.13 [95% CI 0.02-0.75] p = 0.023), and a trend was observed between CYP2D6*4 and higher maintenance dose of carvedilol (OR 2.94 [95% CI 0.84-10.30] p = 0.093). None of the patients that carried CYP2D6*4 achieved the recommended target dose of metoprolol (200 mg/day). Consistent with the role of CYP2D6 in the metabolism of metoprolol, the tolerated maintenance dose of metoprolol was lower in CYP2D6*4 carriers compared to non-carriers. Consistent with the role of CYP2D6 in activation of carvedilol, tolerated maintenance dose of carvedilol was higher in CYP2D6*4 carriers compared to non-carriers. Further investigation is warranted to ascertain the potential of CYP2D6 as a potential predictive biomarker of beta-blocker maintenance dose in heart failure patients.

  7. Photocatalytic degradation kinetics and mechanism of environmental pharmaceuticals in aqueous suspension of TiO{sub 2}: A case of {beta}-blockers

    Energy Technology Data Exchange (ETDEWEB)

    Yang Hai [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Kehua Street, Tianhe District, Guangzhou 510640 (China); Graduate School of Chinese Academy of Sciences, Beijing 100049 (China); An Taicheng, E-mail: antc99@gig.ac.cn [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Kehua Street, Tianhe District, Guangzhou 510640 (China); Li Guiying [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Kehua Street, Tianhe District, Guangzhou 510640 (China); Song Weihua; Cooper, William J. [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, CA 92697-2175 (United States); Luo Haiying [State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Resources Utilization and Protection, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Kehua Street, Tianhe District, Guangzhou 510640 (China); Graduate School of Chinese Academy of Sciences, Beijing 100049 (China); Guangzhou Product Quality Supervision and Testing Institute, National Centre for Quality Supervision and Testing of Processed Food (Guangzhou), Guangzhou 510110 (China); Guo Xindong [Guangzhou Product Quality Supervision and Testing Institute, National Centre for Quality Supervision and Testing of Processed Food (Guangzhou), Guangzhou 510110 (China)

    2010-07-15

    This study investigated the photocatalytic degradation of three {beta}-blockers in TiO{sub 2} suspensions. The disappearance of the compounds followed pseudo-first-order kinetics according to the Langmuir-Hinshelwood model and the rate constants were 0.075, 0.072 and 0.182 min{sup -1} for atenolol, metoprolol and propranolol, respectively. After 240 min irradiation, the reaction intermediates were completely mineralized to CO{sub 2} and the nitrogen was predominantly as NH{sub 4}{sup +}. The influence of initial pH and {beta}-blocker concentration on the kinetics was also studied. From adsorption studies it appears that the photocatalytic degradation occurred mainly on the surface of TiO{sub 2}. Further studies indicated that surface reaction with {center_dot}OH radical was principally responsible for the degradation of these three {beta}-blockers. The major degradation intermediates were identified by HPLC/MS analysis. Cleavage of the side chain and the addition of the hydroxyl group to the parent compounds were found to be the two main degradation pathways for all three {beta}-blockers.

  8. Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction : individual patient data meta-analysis

    NARCIS (Netherlands)

    Kotecha, Dipak; Manzano, Luis; Krum, Henry; Rosano, Giuseppe; Holmes, Jane; Altman, Douglas G.; Collins, Peter D.; Packer, Milton; Wikstrand, John; Coats, Andrew J. S.; Cleland, John G. F.; Kirchhof, Paulus; von Lueder, Thomas G.; Rigby, Alan S.; Andersson, Bert; Lip, Gregory Y. H.; van Veldhuisen, Dirk J.; Shibata, Marcelo C.; Wedel, Hans; Boehm, Michael; Flather, Marcus D.

    2016-01-01

    OBJECTIVES To determine the efficacy and tolerability of beta blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. DESIGN Prospectively designed meta-analysis of

  9. A moving blocker-based strategy for simultaneous megavoltage and kilovoltage scatter correction in cone-beam computed tomography image acquired during volumetric modulated arc therapy

    International Nuclear Information System (INIS)

    Ouyang, Luo; Lee, Huichen Pam; Wang, Jing

    2015-01-01

    Purpose: To evaluate a moving blocker-based approach in estimating and correcting megavoltage (MV) and kilovoltage (kV) scatter contamination in kV cone-beam computed tomography (CBCT) acquired during volumetric modulated arc therapy (VMAT). Methods and materials: During the concurrent CBCT/VMAT acquisition, a physical attenuator (i.e., “blocker”) consisting of equally spaced lead strips was mounted and moved constantly between the CBCT source and patient. Both kV and MV scatter signals were estimated from the blocked region of the imaging panel, and interpolated into the unblocked region. A scatter corrected CBCT was then reconstructed from the unblocked projections after scatter subtraction using an iterative image reconstruction algorithm based on constraint optimization. Experimental studies were performed on a Catphan® phantom and an anthropomorphic pelvis phantom to demonstrate the feasibility of using a moving blocker for kV–MV scatter correction. Results: Scatter induced cupping artifacts were substantially reduced in the moving blocker corrected CBCT images. Quantitatively, the root mean square error of Hounsfield units (HU) in seven density inserts of the Catphan phantom was reduced from 395 to 40. Conclusions: The proposed moving blocker strategy greatly improves the image quality of CBCT acquired with concurrent VMAT by reducing the kV–MV scatter induced HU inaccuracy and cupping artifacts

  10. Cholinesterases: structure of the active site and mechanism of the effect of cholinergic receptor blockers on the rate of interaction with ligands

    Energy Technology Data Exchange (ETDEWEB)

    Antokhin, A M; Gainullina, E T; Taranchenko, V F [Federal State Agency ' 27 Scientific Centre of Ministry of Defence of the Russian Federation' (Russian Federation); Ryzhikov, S B; Yavaeva, D K [Department of Physics, M.V.Lomonosov Moscow State University (Russian Federation)

    2010-10-19

    Modern views on the structure of cholinesterase active sites and the mechanism of their interaction with organophosphorus inhibitors are considered. The attention is focused on the mechanism of the effect of cholinergic receptor blockers, acetylcholine antagonists, on the rate of interaction of acetylcholine esterase with organophosphorus inhibitors.

  11. Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Niko Bekjarovski

    2013-09-01

    How to cite this article: Bekjarovski NG. Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature. Asia Pac J Med Toxicol 2013;2:114-6.

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

    Directory of Open Access Journals (Sweden)

    Luong KV

    2012-12-01

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

  13. Rational design, efficient syntheses and biological evaluation of N,N '-symmetrically bis-substituted butylimidazole analogs as a new class of potent Angiotensin II receptor blockers

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

    Roč. 62, Apr (2013), s. 352-370 ISSN 0223-5234 Institutional support: RVO:61388963 Keywords : AT1 receptor blockers * N,N '-Bis-alkylated butylimidazole analogs * synthesis * Wittig reaction * hydroxymethylation * structure elucidation Subject RIV: CC - Organic Chemistry Impact factor: 3.432, year: 2013

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

    DEFF Research Database (Denmark)

    NN, NN; Yusuf, S; Teo, K

    2008-01-01

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

  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...

  16. Use of Beta-Blockers and Aspirin in Acute Coronary Syndromes by Patient Renal Function in the Military Healthcare Systems, National Capital Area

    National Research Council Canada - National Science Library

    Abbott, Kevin C

    2005-01-01

    ...) hospital system from 2001 through 2004. Use of beta-blockers (BB) and aspirin (ASA) at the time of discharge after AMI was assessed according to serum creatinine level, stratified by admission to the coronary care unit (CCU) vs. other wards...

  17. Agricultural Producer Certificates

    Data.gov (United States)

    Montgomery County of Maryland — A Certified Agricultural Producer, or representative thereof, is an individual who wishes to sell regionally-grown products in the public right-of-way. A Certified...

  18. Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials.

    Science.gov (United States)

    Cleland, John G F; Bunting, Karina V; Flather, Marcus D; Altman, Douglas G; Holmes, Jane; Coats, Andrew J S; Manzano, Luis; McMurray, John J V; Ruschitzka, Frank; van Veldhuisen, Dirk J; von Lueder, Thomas G; Böhm, Michael; Andersson, Bert; Kjekshus, John; Packer, Milton; Rigby, Alan S; Rosano, Giuseppe; Wedel, Hans; Hjalmarson, Åke; Wikstrand, John; Kotecha, Dipak

    2018-01-01

    Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

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

    Science.gov (United States)

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

    2017-12-15

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

  20. Effectiveness of a management program for outpatient clinic or remote titration of beta-blockers in CRT patients: The RESTORE study.

    Science.gov (United States)

    D'Onofrio, Antonio; Palmisano, Pietro; Rapacciuolo, Antonio; Ammendola, Ernesto; Calò, Leonardo; Ruocco, Antonio; Bianchi, Valter; Maresca, Fabio; Del Giorno, Giuseppe; Martino, Annamaria; Mauro, Ciro; Campari, Monica; Valsecchi, Sergio; Accogli, Michele

    2017-06-01

    Many patients fail to receive β-blockers before cardiac resynchronization therapy defibrillator (CRT-D) implantation, or receive them at a suboptimal dose, and require optimization after implantation. We assessed the effectiveness of a structured program for β-blocker titration in CRT-D patients followed up by means of conventional in-clinic visits or remote monitoring. 130 patients undergoing CRT implantation and treated according to the standard practice of the centers were included as a control group. A second group of 124 CRT-D candidates (Study Group) underwent up-titration visits every 2weeks after implantation (target dose: 10mg/day of bisoprolol or 50mg/day of carvedilol). In the Study Group, remote monitoring was undertaken in 66 patients, who received additional equipment for daily transmission of weight and blood pressure data, and scheduled titration telephone calls. In the Control Group, the maximal dose of β-blockers was being administered to 12 (9%) patients on implantation and 21 (16%) on 6-month follow-up examination (p>0.05). In the Study Group, 25 (20%) patients were receiving the maximal dose of β-blockers on implantation and 72 (58%) on follow-up examination (ptitration (versus 38% of patients followed up conventionally, ptitration increased the number of patients reaching the target dose and improved the response to the therapy. The use of remote monitoring and daily transfer of weight and blood pressure data facilitated β-blocker titration. URL: http://clinicaltrials.gov/ Identifier: NCT02173028. Copyright © 2017. Published by Elsevier B.V.

  1. The Jervell and Lange-Nielsen syndrome; atrial pacing combined with ß-blocker therapy, a favorable approach in young high-risk patients with long QT syndrome?

    Science.gov (United States)

    Früh, Andreas; Siem, Geir; Holmström, Henrik; Døhlen, Gaute; Haugaa, Kristina H

    2016-11-01

    Patients with Jervell and Lange-Nielsen syndrome (JLNS) exhibit severe phenotypes that are characterized by congenital deafness, very long QT intervals, and high risk of life-threatening arrhythmias. Current treatment strategies include high doses of beta-blocker medication, left cardiac sympathetic denervation, and ICD placement, which is challenging in young children. The purpose of this study was to evaluate the safety and effect of pacing in addition to beta-blocker treatment in children with JLNS. All genetically confirmed patients with JLNS born since 1999 in Norway were included in the study. Data on history of long QT syndrome-related symptoms, QT interval, and beta-blocker and pacemaker treatment were recorded. A total of 9 patients with QT intervals ranging from 510 to 660 ms were identified. Eight patients developed long QT syndrome-related symptoms, and 1 patient died before diagnosis. The survivors received beta-blocker medication. Seven patients also received a pacemaker; 1 had a ventricular lead and 6 had atrial leads. The patient with the ventricular lead died during follow-up. The 6 patients with atrial leads survived without events at a mean follow-up of 6.9 years after pacemaker implantation. Two patients received prophylactic upgrade to a 2-chamber ICD. No arrhythmic events occurred in 6 very young JLNS patients who received atrial pacing in combination with increased doses of beta-blockers during 7-year follow-up. If confirmed in additional patients, this treatment strategy may prevent life-threatening arrhythmias in this high-risk patient group and may act as a bridge to insertion of a 2-chamber ICD when left cardiac sympathetic denervation is not available. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Cost-Effectiveness of TNF-Blocker Injection Spacing for Patients with Established Rheumatoid Arthritis in Remission: An Economic Evaluation from the Spacing of TNF-Blocker Injections in Rheumatoid Arthritis Trial.

    Science.gov (United States)

    Vanier, Antoine; Mariette, Xavier; Tubach, Florence; Fautrel, Bruno

    2017-04-01

    In patients with rheumatoid arthritis in remission, a disease activity-driven tapering of adalimumab or etanercept relying on progressive injection spacing has not been shown to be equivalent to a maintenance strategy at full dose in terms of disease activity in the Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study (STRASS) trial. To evaluate the cost-effectiveness of such a spacing strategy based on the data of the STRASS trial. This is a cost-utility analysis of the STRASS trial, a French multicenter 18-month equivalence randomized open-label controlled trial that included patients at stable dose for at least 1 year, in remission for at least 6 months. Effectiveness was assessed in quality-adjusted life-years (QALYs). Costs involved in the study period were assessed from a payer perspective. The decremental cost-effectiveness ratio (DCER) was calculated in the complete cases sample (n = 98). Several sensitivity analyses were conducted and the impact of missing data on DCER estimate was investigated. An acceptability analysis was performed. In the spacing arm, TNF-blockers were stopped for 34.1% of the patients, tapered for 43.2%, and maintained at full dose for 18.2%. The spacing strategy was associated with less QALYs gain (mean difference of -0.158; 95% confidence interval [CI] -0.085 to -0.232) and reduced costs (mean difference of -€8,440; 95% CI -6,507 to -10,212). The estimated DCER of the spacing strategy over the maintenance at full dose was €53,417 saved per QALY lost (95% CI 32,230 to 104,700). The spacing strategy appears cost-effective, but the acceptability of such a QALY loss reported to the cost avoided remains to be evaluated, because no consensual threshold has been determined for willingness to accept as compared with willingness to pay. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  3. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies.

    Science.gov (United States)

    Graudins, Andis; Lee, Hwee Min; Druda, Dino

    2016-03-01

    Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock. © 2015 The British Pharmacological Society.

  4. Producing superhydrophobic roof tiles

    International Nuclear Information System (INIS)

    Carrascosa, Luis A M; Facio, Dario S; Mosquera, Maria J

    2016-01-01

    Superhydrophobic materials can find promising applications in the field of building. However, their application has been very limited because the synthesis routes involve tedious processes, preventing large-scale application. A second drawback is related to their short-term life under outdoor conditions. A simple and low-cost synthesis route for producing superhydrophobic surfaces on building materials is developed and their effectiveness and their durability on clay roof tiles are evaluated. Specifically, an organic–inorganic hybrid gel containing silica nanoparticles is produced. The nanoparticles create a densely packed coating on the roof tile surface in which air is trapped. This roughness produces a Cassie–Baxter regime, promoting superhydrophobicity. A surfactant, n-octylamine, was also added to the starting sol to catalyze the sol–gel process and to coarsen the pore structure of the gel network, preventing cracking. The application of ultrasound obviates the need to use volatile organic compounds in the synthesis, thereby making a ‘green’ product. It was also demonstrated that a co-condensation process effective between the organic and inorganic species is crucial to obtain durable and effective coatings. After an aging test, high hydrophobicity was maintained and water absorption was completely prevented for the roof tile samples under study. However, a transition from a Cassie–Baxter to a Wenzel state regime was observed as a consequence of the increase in the distance between the roughness pitches produced by the aging of the coating. (paper)

  5. Producing superhydrophobic roof tiles.

    Science.gov (United States)

    Carrascosa, Luis A M; Facio, Dario S; Mosquera, Maria J

    2016-03-04

    Superhydrophobic materials can find promising applications in the field of building. However, their application has been very limited because the synthesis routes involve tedious processes, preventing large-scale application. A second drawback is related to their short-term life under outdoor conditions. A simple and low-cost synthesis route for producing superhydrophobic surfaces on building materials is developed and their effectiveness and their durability on clay roof tiles are evaluated. Specifically, an organic-inorganic hybrid gel containing silica nanoparticles is produced. The nanoparticles create a densely packed coating on the roof tile surface in which air is trapped. This roughness produces a Cassie-Baxter regime, promoting superhydrophobicity. A surfactant, n-octylamine, was also added to the starting sol to catalyze the sol-gel process and to coarsen the pore structure of the gel network, preventing cracking. The application of ultrasound obviates the need to use volatile organic compounds in the synthesis, thereby making a 'green' product. It was also demonstrated that a co-condensation process effective between the organic and inorganic species is crucial to obtain durable and effective coatings. After an aging test, high hydrophobicity was maintained and water absorption was completely prevented for the roof tile samples under study. However, a transition from a Cassie-Baxter to a Wenzel state regime was observed as a consequence of the increase in the distance between the roughness pitches produced by the aging of the coating.

  6. TRIAL: Producing Media Catalogs.

    Science.gov (United States)

    McWeeney, Mark G.

    TRIAL (Technique for Retrieving Information from Abstracts of Literature) is an information storage and retrieval system which can be used by school media specialists to produce indexes of non-print materials. This manual provides a step by step approach for media specialists to automate their non-print holdings. These procedures can also be…

  7. Methods for producing diterpenes

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention discloses that by combining different di TPS enzymes of class I and class II different diterpenes may be produced including diterpenes not identified in nature. Surprisingly it is revealed that a di TPS enzyme of class I of one species may be combined with a di TPS enzyme...

  8. Producing Civil Society

    DEFF Research Database (Denmark)

    Feldt, Liv Egholm; Hein Jessen, Mathias

    ’ and as such dominates our way of thinking about civil society. Yet, this view hinders the understanding of how civil society is not a pre-existing or given sphere, but a sphere which is constantly produced both discursively, conceptually and practically. Through two examples; 1,the case of philanthropy in the beginning...

  9. (PHB)-producing bacteria

    African Journals Online (AJOL)

    Isolation and characterization of two novel polyhydroxybutyrate (PHB)-producing bacteria. ... subsequently studied using phenotype microarray panels which allowed the testing of the effect of more than 90 different carbon, nitrogen, sulfur and phosphorus sources as well as pH on the growth characteristics of these strains.

  10. Amlodipine versus angiotensin II receptor blocker; control of blood pressure evaluation trial in diabetics (ADVANCED-J

    Directory of Open Access Journals (Sweden)

    Ikeda Shunya

    2006-10-01

    Full Text Available Abstract Background The coexistence of type 2 diabetes mellitus and hypertension increases the risk of cardiovascular diseases. The U.K. Prospective Diabetes Study has shown that blood pressure control as well as blood glucose control is efficient for prevention of complications in hypertensive patients with diabetes mellitus. However, some reports have shown that it is difficult to control the blood pressure and the concomitant use of a plurality of drugs is needed in hypertensive patients with diabetes mellitus. In recent years renin-angiotensin system depressants are increasingly used for the blood pressure control in diabetic patients. Particularly in Japan, angiotensin II (A II antagonists are increasingly used. However, there is no definite evidence of the point of which is efficient for the control, the increase in dose of A II antagonist or the concomitant use of another drug, in hypertensive patients whose blood pressure levels are inadequately controlled with A II antagonist. Methods/Design Hypertensive patients of age 20 years or over with type 2 diabetes mellitus who have been treated by the single use of AII antagonist at usual doses for at least 8 weeks or patients who have been treated by the concomitant use of AII antagonist and an antihypertensive drug other than calcium channel blockers and ACE inhibitors at usual doses for at least 8 weeks are included. Discussion We designed a multi-center, prospective, randomized, open label, blinded-endpoint trial, ADVANCED-J, to compare the increases in dose of A II antagonist and the concomitant use of a Ca-channel blocker (amlodipine and A II antagonist in hypertensive patients with diabetes mellitus, whose blood pressure levels were inadequately controlled with A II antagonist. This study is different from the usual previous studies in that home blood pressures are assessed as indicators of evaluation of blood pressure. The ADVANCED-J study may have much influence on selection of

  11. Beta blocker use in subjects with type 2 diabetes mellitus and systolic heart failure does not worsen glycaemic control

    Directory of Open Access Journals (Sweden)

    Wai Bryan

    2012-02-01

    Full Text Available Abstract Background The prognostic benefits of beta-blockers (BB in patients with systolic heart failure (SHF are known but despite this, in patients with diabetes they are underutilized. The aim of this study was to assess the effect of beta-blockers (BB on glycaemic control in patients with Type 2 Diabetes (T2DM and systolic heart failure (SHF stratified to beta-1 selective (Bisoprolol vs. nonselective BB (Carvedilol. Methods This observational, cohort study was conducted in patients with T2DM and SHF attending an Australian tertiary teaching hospital's heart failure services. The primary endpoint was glycaemic control measured by glycosylated haemoglobin (HbA1c at initiation and top dose of BB. Secondary endpoints included microalbuminuria, changes in lipid profile and estimated glomerular filtration rate (eGFR. Results 125 patients were assessed. Both groups were well matched for gender, NYHA class and use of guideline validated heart failure and diabetic medications. The mean treatment duration was 1.9 ± 1.1 years with carvedilol and 1.4 ± 1.0 years with bisoprolol (p = ns. The carvedilol group achieved a reduction in HbA1c (7.8 ± 0.21% to 7.3 ± 0.17%, p = 0.02 whereas the bisoprolol group showed no change in HbA1c (7.0 ± 0.20% to 6.9 ± 0.23%, p = 0.92. There was no significant difference in the change in HbA1c from baseline to peak BB dose in the carvedilol group compared to the bisoprolol group. There was a similar deterioration in eGFR, but no significant changes in lipid profile or microalbuminuria in both groups (p = ns. Conclusion BB use did not worsen glycaemic control, lipid profile or albuminuria status in subjects with SHF and T2DM. Carvedilol significantly improved glycemic control in subjects with SHF and T2DM and this improvement was non significantly better than that obtained with bisoprolol. BB's should not be withheld from patients with T2DM and SHF.

  12. On Biophysical Properties and Sensitivity to Gap Junction Blockers of Connexin 39 Hemichannels Expressed in HeLa Cells

    Science.gov (United States)

    Vargas, Anibal A.; Cisterna, Bruno A.; Saavedra-Leiva, Fujiko; Urrutia, Carolina; Cea, Luis A.; Vielma, Alex H.; Gutierrez-Maldonado, Sebastian E.; Martin, Alberto J. M.; Pareja-Barrueto, Claudia; Escalona, Yerko; Schmachtenberg, Oliver; Lagos, Carlos F.; Perez-Acle, Tomas; Sáez, Juan C.

    2017-01-01

    Although connexins (Cxs) are broadly expressed by cells of mammalian organisms, Cx39 has a very restricted pattern of expression and the biophysical properties of Cx39-based channels [hemichannels (HCs) and gap junction channels (GJCs)] remain largely unknown. Here, we used HeLa cells transfected with Cx39 (HeLa-Cx39 cells) in which intercellular electrical coupling was not detected, indicating the absence of GJCs. However, functional HCs were found on the surface of cells exposed to conditions known to increase the open probability of other Cx HCs (e.g., extracellular divalent cationic-free solution (DCFS), extracellular alkaline pH, mechanical stimulus and depolarization to positive membrane potentials). Cx39 HCs were blocked by some traditional Cx HC blockers, but not by others or a pannexin1 channel blocker. HeLa-Cx39 cells showed similar resting membrane potentials (RMPs) to those of parental cells, and exposure to DCFS reduced RMPs in Cx39 transfectants, but not in parental cells. Under these conditions, unitary events of ~75 pS were frequent in HeLa-Cx39 cells and absent in parental cells. Real-time cellular uptake experiments of dyes with different physicochemical features, as well as the application of a machine-learning approach revealed that Cx39 HCs are preferentially permeable to molecules characterized by six categories of descriptors, namely: (1) electronegativity, (2) ionization potential, (3) polarizability, (4) size and geometry, (5) topological flexibility and (6) valence. However, Cx39 HCs opened by mechanical stimulation or alkaline pH were impermeable to Ca2+. Molecular modeling of Cx39-based channels suggest that a constriction present at the intracellular portion of the para helix region co-localizes with an electronegative patch, imposing an energetic and steric barrier, which in the case of GJCs may hinder channel function. Results reported here demonstrate that Cx39 form HCs and add to our understanding of the functional roles of Cx39 HCs

  13. Chronic effects assessment and plasma concentrations of the β-blocker propranolol in fathead minnows (Pimephales promelas)

    International Nuclear Information System (INIS)

    Giltrow, Emma; Eccles, Paul D.; Winter, Matthew J.; McCormack, Paul J.; Rand-Weaver, Mariann; Hutchinson, Thomas H.; Sumpter, John P.

    2009-01-01

    The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker (β-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590 ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10 mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4 mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC hatchability and LOEC female GSI values of 0.1 mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC m ale wet weight value of 1.0 mg/L, and the LOEC r eproduction value was 1.0 mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0 mg/L were 0.34 and 15.00 mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84 mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0 mg/L were greater than the human therapeutic plasma concentration

  14. Chronic effects assessment and plasma concentrations of the {beta}-blocker propranolol in fathead minnows (Pimephales promelas)

    Energy Technology Data Exchange (ETDEWEB)

    Giltrow, Emma [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Eccles, Paul D. [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Winter, Matthew J.; McCormack, Paul J. [AstraZeneca Safety, Health and Environment, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon TQ5 8BA (United Kingdom); Rand-Weaver, Mariann [Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom); Hutchinson, Thomas H. [Natural Environmental Research Council, Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3DH (United Kingdom); Sumpter, John P., E-mail: john.sumpter@brunel.ac.uk [Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH (United Kingdom)

    2009-11-27

    The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker ({beta}-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590 ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10 mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4 mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC{sup hatchability} and LOEC{sup female} {sup GSI} values of 0.1 mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC{sup m}ale wet weight value of 1.0 mg/L, and the LOEC{sup r}eproduction value was 1.0 mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0 mg/L were 0.34 and 15.00 mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84 mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0 mg/L were greater than the human

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

    Science.gov (United States)

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

    2017-05-15

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

  16. Potassium iodide as a thyroid blocker--Three Mile Island to today

    International Nuclear Information System (INIS)

    Halperin, J.A.

    1989-01-01

    The Three Mile Island (TMI) nuclear emergency in the U.S. in March 1979 marked the first occasion when use of potassium iodide (KI) was considered for thyroid blocking of the population in the vicinity of a potentially serious release of fission products from a nuclear power reactor. In face of a demand that could not be satisfied by commercial supplies of low-dose KI drug products from the U.S. pharmaceutical industry, the Food and Drug Administration directed the manufacture and stockpiling of sufficient quantities of saturated solution of potassium iodide (SSKI) to provide protection for one million people in the event of a large-scale release of radioiodines. Although the drug was not used, the experience of producing, stockpiling, and making ready for use a large quantity of the drug resulted in significant public policy, regulatory, and logistical issues. A number of these issues have been resolved through scientific debate and consensus, development of official guidance regarding the proper role of KI in nuclear emergencies, and the approval of New Drug Applications for KI products specifically intended for thyroid blocking in nuclear emergencies. Other issues regarding broad-scale implementation of the guidelines remain today. This paper traces the history of the development and implementation of the use of KI from pre-TMI to the present

  17. Potassium iodide as a thyroid blocker--Three Mile Island to today.

    Science.gov (United States)

    Halperin, J A

    1989-05-01

    The Three Mile Island (TMI) nuclear emergency in the U.S. in March 1979 marked the first occasion when use of potassium iodide (KI) was considered for thyroid blocking of the population in the vicinity of a potentially serious release of fission products from a nuclear power reactor. In face of a demand that could not be satisfied by commercial supplies of low-dose KI drug products from the U.S. pharmaceutical industry, the Food and Drug Administration directed the manufacture and stockpiling of sufficient quantities of saturated solution of potassium iodide (SSKI) to provide protection for one million people in the event of a large-scale release of radioiodines. Although the drug was not used, the experience of producing, stockpiling, and making ready for use a large quantity of the drug resulted in significant public policy, regulatory, and logistical issues. A number of these issues have been resolved through scientific debate and consensus, development of official guidance regarding the proper role of KI in nuclear emergencies, and the approval of New Drug Applications for KI products specifically intended for thyroid blocking in nuclear emergencies. Other issues regarding broad-scale implementation of the guidelines remain today. This paper traces the history of the development and implementation of the use of KI from pre-TMI to the present.

  18. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats.

    Science.gov (United States)

    Lozano-Cuenca, J; González-Hernández, A; López-Canales, O A; Villagrana-Zesati, J R; Rodríguez-Choreão, J D; Morín-Zaragoza, R; Castillo-Henkel, E F; López-Canales, J S

    2017-08-07

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (Pclobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

  19. Producing colloids with microfluidics

    Science.gov (United States)

    Pannacci, Nicolas; Willaime, Herve; Tabeling, Patrick

    2008-11-01

    Submicronic emulsions are commonly used in pharmaceutical, food, cosmetic and material industries. Standard microfluidic tool is particularly convenient to produce in a very controlled way either droplets of typical diameter ranging from 10 to 300 microns with a perfect monodispersity (nanodrops in a way that is slightly dependent on the fluids used. The control on such a flow authorizes the adjustment of the diameter of the colloids formed. We will show brownian particles from 860 nm to 1.3 μm in diameter obtained in such way and their clustering into crystals thanks to their high monodispersity. These first experimental results are very promising and make evident the great potential of micro and nano-fluidics to produce nano-emulsions or colloids with very controlled size that metamaterials can require.

  20. Means for producing gas

    Energy Technology Data Exchange (ETDEWEB)

    Reichhelm, G.L.

    1929-01-22

    This patent describes a gas-generating apparatus which works in combination with a gas-generating receptacle. The process requires a means for supplying finely divided carbon to said receptable, means for supplying a flame under pressure to hold said carbon in suspension, a conduit for conducting the combustible gas produced from said receptacle, and synchronously operating mechanical means for controlling said carbon-supplying means and said flame-supplying means.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-06-15

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

  2. Investigation of Calcium Channel Blockers as Antiprotozoal Agents and Their Interference in the Metabolism of Leishmania (L. infantum

    Directory of Open Access Journals (Sweden)

    Juliana Quero Reimão

    2016-01-01

    Full Text Available Leishmaniasis and Chagas disease are neglected parasitic diseases endemic in developing countries; efforts to find new therapies remain a priority. Calcium channel blockers (CCBs are drugs in clinical use for hypertension and other heart pathologies. Based on previous reports about the antileishmanial activity of dihydropyridine-CCBs, this work aimed to investigate whether the in vitro anti-Leishmania infantum and anti-Trypanosoma cruzi activities of this therapeutic class would be shared by other non-dihydropyridine-CCBs. Except for amrinone, our results demonstrated antiprotozoal activity for fendiline, mibefradil, and lidoflazine, with IC50 values in a range between 2 and 16 μM and Selectivity Index between 4 and 10. Fendiline demonstrated depolarization of mitochondrial membrane potential, with increased reactive oxygen species production in amlodipine and fendiline treated Leishmania, but without plasma membrane disruption. Finally, in vitro combinations of amphotericin B, miltefosine, and pentamidine against L. infantum showed in isobolograms an additive interaction when these drugs were combined with fendiline, resulting in overall mean sum of fractional inhibitory concentrations between 0.99 and 1.10. These data demonstrated that non-dihydropyridine-CCBs present antiprotozoal activity and could be useful candidates for future in vivo efficacy studies against Leishmaniasis and Chagas’ disease.

  3. Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs

    Directory of Open Access Journals (Sweden)

    Juliana Quero Reimão

    2011-12-01

    Full Text Available The need for drug combinations to treat visceral leishmaniasis (VL arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs, sum of FICs (ΣFICs and the overall mean ΣFIC were calculated for each combination. Graphical isobologram analysis showed that the combination of nimodipine and glucantime was the most promising in amastigotes with an overall mean ΣFIC value of 0.79. Interactions between CCBs and the anti-leishmanial drugs were classified as indifferent according to the overall mean ΣFIC and the isobologram graphic analysis.

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

    Directory of Open Access Journals (Sweden)

    Ibrahim F. Benter

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jennifer W. Bea

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yuki Hamano

    2011-09-01

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

  7. Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis.

    Science.gov (United States)

    Ashida, K; Sakurai, Y; Hori, T; Kudou, K; Nishimura, A; Hiramatsu, N; Umegaki, E; Iwakiri, K

    2016-01-01

    Vonoprazan is a novel potassium-competitive acid blocker which may provide clinical benefit in acid-related disorders. To verify the non-inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis (EE), and to establish its long-term safety and efficacy as maintenance therapy. In this multicentre, randomised, double-blind, parallel-group comparison study, patients with endoscopically confirmed EE (LA Classification Grades A-D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re-randomised into a long-term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks. Of the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long-term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non-inferiority of vonoprazan (P lansoprazole in EE was verified in the comparison study, and vonoprazan was well-tolerated and effective during the long-term maintenance study. © 2015 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

  8. Spectrofluorometric determination of some beta-blockers in tablets and human plasma using 9,10-dimethoxyanthracene-2-sodium sulfonate.

    Science.gov (United States)

    Abdine, H; Sultan, M A; Hefnawy, M M; Belal, F

    2005-04-01

    A simple and sensitive spectrofluorometric method was developed for the quantitative determination of some beta-blockers, namely arotinolol, atenolol and labetalol as hydrochloride salts. The method is based on the reaction of these drugs as n-electron donors with the fluorogenic reagent 9,10-dimethoxy-2-anthracene sulfonate (DMAS) as pi-acceptor in acidic medium. The obtained ion-pairs were extracted into chloroform and measured spectrofluorometrically at 452 nm after excitation at 385 nm. The fluorescence intensity-concentration plots are rectilinear over the ranges of 0.5-5 microg x ml(1), 1.0-11.0 microg x ml(1) and 0.6-6.4 microg x ml(1) for labetalol, atenolol and arotinolol, respectively. The different parameters affecting the reaction pathway were thoroughly studied and optimized. No interference was observed from the common pharmaceutical excipients. The proposed method was successfully applied to the analysis of tablets and the results were statistically compared with those obtained by reference methods. The method was further extended to the in vitro determination of the drugs in spiked human plasma, the % recoveries (n = 3) ranged from 96.98 +/- 1.55 to 98.28 +/- 2.19. A proposal of the reaction pathway was postulated.

  9. Potentiation of Opioid-Induced Analgesia by L-Type Calcium Channel Blockers: Need for Clinical Trial in Cancer Pain

    Directory of Open Access Journals (Sweden)

    S Basu Ray

    2008-01-01

    Full Text Available Previous reports indicate that the analgesic effect of opioids is due to both closure of specific voltage-gated calcium channels (N- and P/Q-types and opening of G protein-coupled inwardly rectifying potassium channels (GIRKs in neurons concerned with transmission of pain. However, administration of opioids leads to unacceptable levels of side effects, particularly at high doses. Thus, current research is directed towards simultaneously targeting other voltage-gated calcium channels (VGCCs like the L-type VGCCs or even other cell signaling mechanisms, which would aug-ment opioid-mediated analgesic effect without a concurrent increase in the side effects. Unfortunately, the results of these studies are often conflicting considering the different experimental paradigms (variable drug selection and their doses and also the specific pain test used for studying analgesia adopted by researchers. The present review focuses on some of the interesting findings regarding the analgesic effect of Opioids + L-VGCC blockers and suggests that time has come for a clinical trial of this combination of drugs in the treatment of cancer pain.

  10. Assessment of the relationship between the molecular properties of calcium channel blockers and plasma protein binding data

    Directory of Open Access Journals (Sweden)

    Odović Jadranka V.

    2017-01-01

    Full Text Available In this study we investigated the relationship between the calcium channel blockers (CCBs, amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem, and their calculated molecular descriptors: polar surface area (PSA, molecular weight (Mw, volume value (Vol, aqueous solubility data (logS, lipophilicity (logP, acidity (pKa values and plasma protein binding (PPB data, obtained from relevant literature. The relationships between the computed molecular properties of selected CCBs and their PPB data were investigated by simple linear regression analysis that revealed very low correlations (R2<0.35. When multiple linear regression (MLR analysis was applied to investigate reliable correlations between the CCBs’ calculated molecular descriptors and PPB data, the best correlations were found for the relationships between CCBs, and PPB data and lipophilicity, and with application of the molecular descriptor (Mw, Vol, or pKa data as additional independent variables (R2=0.623; R2=0.741; R2=0.657, respectively, with an acceptable probability value (P<0.05, confirming that lipophilicity, together with other molecular properties, are essential for the drugs’ PPB. We conclude that this could be considered as an additional in vitro approach for modeling CCBs. [Projekat Ministarstva nauke Republike Srbije, br. TR34031

  11. Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus

    Directory of Open Access Journals (Sweden)

    Jinmi Koo

    2015-09-01

    Full Text Available BackgroundIn mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN. Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions.MethodsWe examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2 gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC knock-in mice using a real-time bioluminescence measurement system.ResultsAdministration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms.ConclusionThese findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

  12. Effects of angiotensin II type 1 receptor blocker on bones in mice with type 1 diabetes induced by streptozotocin.

    Science.gov (United States)

    Zhang, Yan; Diao, Teng-Yue; Gu, Sa-Sa; Wu, Shu-Yan; Gebru, Yoseph A; Chen, Xi; Wang, Jing-Yu; Ran, Shu; Wong, Man-Sau

    2014-09-01

    This study was performed to address the pathological roles of the skeletal renin-angiotensin system (RAS) in type 1 diabetes-induced osteoporosis and the effects of the angiotensin II type 1 receptor blocker losartan on bones in diabetic mice. Bone histomorphology was detected by H&E staining, Safranin O staining and X-ray radiography. Micro-CT was performed for the analysis of bone parameters. Gene and protein expression were determined by RT-PCR and immunoblotting. Type 1 diabetic mice displayed osteopenia phenotype, and losartan treatment had no osteoprotective effects on diabetic mice as shown by the reduction of bone mineral density and microarchitectural parameters at the proximal metaphysis of the tibia. The mRNA expression of AGT, renin receptor and ACE, and protein expression of renin and AT1R were markedly up-regulated in the bones of vehicle-treated diabetic mice compared to those of non-diabetic mice. The treatment with losartan further significantly increased the expression of AGT, renin, angiotensin II and AT1R, and reduced the expression of AT2R receptor as compared to those of diabetic mice. Local bone RAS functionally played a role in the development of type 1 diabetic osteoporosis, and losartan had no bone-sparing function in diabetes mice because of enhance skeletal RAS activity. © The Author(s) 2013.

  13. Adsorption and Photocatalytic Decomposition of the β-Blocker Metoprolol in Aqueous Titanium Dioxide Suspensions: Kinetics, Intermediates, and Degradation Pathways

    Directory of Open Access Journals (Sweden)

    Violette Romero

    2013-01-01

    Full Text Available This study reports the photocatalytic degradation of the β-blocker metoprolol (MET using TiO2 suspended as catalyst. A series of photoexperiments were carried out by a UV lamp, emitting in the 250–400 nm range, providing information about the absorption of radiation in the photoreactor wall. The influence of the radiation wavelength on the MET photooxidation rate was investigated using a filter cutting out wavelengths shorter than 280 nm. Effects of photolysis and adsorption at different initial pH were studied to evaluate noncatalytic degradation for this pharmaceutical. MET adsorption onto titania was fitted to two-parameter Langmuir isotherm. From adsorption results it appears that the photocatalytic degradation can occur mainly on the surface of TiO2. MET removed by photocatalysis was 100% conditions within 300 min, while only 26% was achieved by photolysis at the same time. TiO2 photocatalysis degradation of MET in the first stage of the reaction followed approximately a pseudo-first-order model. The major reaction intermediates were identified by LC/MS analysis such as 3-(propan-2-ylaminopropane-1,2-diol or 3-aminoprop-1-en-2-ol. Based on the identified intermediates, a photocatalytic degradation pathway was proposed, including the cleavage of side chain and the hydroxylation addition to the parent compounds.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Cao, Zemin; Cooper, Mark E

    2012-08-01

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

  16. Role of voltage-gated sodium channel blockers in the treatment of chronic pain: Potential uses in clinical practice based on available evidence.

    Science.gov (United States)

    Alcántara Montero, A; Sánchez Carnerero, C I

    2018-02-26

    Once patients have failed first line therapy, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy. To choose amongst alternative agents, an understanding of pharmacology, pharmacokinetics, and available evidence in targeting various pain conditions is necessary. This article focuses on the use of the carboxamide class of voltage-gated sodium channel blockers (carbamazepine, oxcarbazepine, eslicarbazepine acetate) for adjunct pain medication management; including research updates in pharmacology, pharmacokinetics, and evidence for pain along on this therapeutic group with promising future areas of research. Although evidence for voltage-gated sodium channel blockers in chronic pain management is limited, emerging research has identified this area as promising for additional clinical trials to better guide clinical practice. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. K022: Effect of combination therapy (ANG II antagonist, valsartan and a calcium channel blocker) in a hypertensive model of diabetic nephropathy

    OpenAIRE

    Allen, T.J.; Davis, B.J.; de Gasparo, M.; Cooper, M.E.

    2017-01-01

    Recently, it has been suggested that in the context of diabetes and hypertension, more aggressive blood pressure targets should be considered. To achieve these levels of blood pressure control, it is likely that combination therapy will need to be used. The present study has explored the role of the addition of either a dihydropyridine or a non-dihydropyridine calcium channel blocker (CCB) to Ang II antagonist based treatment in an experimental model of hypertension and diabetes. The doses ch...

  18. Comparison of the effects of an ACE inhibitor and alphabeta blocker on the progression of renal failure with left ventricular hypertrophy: preliminary report.

    Science.gov (United States)

    Suzuki, H; Moriwaki, K; Kanno, Y; Nakamoto, H; Okada, H; Chen, X M

    2001-03-01

    The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and alphabeta blocker in combination with a calcium antagonist on the progression of renal function and left ventricular hypertrophy (LVH) in patients with chronic renal insufficiency and hypertension. The 65 subjects in this study were recruited from a cohort of 316 patients. The main criteria for inclusion were echocardiographic diagnosis of LVH (posterior wall thickness >12 mm) and serum creatinine of more than 1.5 mg/dl. Antihypertensive treatments were switched to the combination of amlodipine at a dose of 5 mg and benazepril at a dose of 2.5 mg daily or the combination of amlodipine at a dose of 5 mg and arotinolol at a dose of 20 mg daily at random irrespective of whether or not patients had been previously treated. The follow-up period was 2 years. Systolic and diastolic blood pressure were significantly reduced from 150/90 +/- 15/11 mmHg to 130/75 +/- 11/9 mmHg (ACE) and the levels of serum creatinine were increased significantly from 1.8 +/- 0.3 to 2.0 +/- 0.4 mg/dl (ACE). In the alphabeta-blocker group, these two values were similar and no significant changes were found. PWT was decreased from 14.2 +/- 0.6 to 12.9 +/- 0.3 cm in alphabeta blocker but was not significantly decreased in the ACE inhibitor group. In conclusion, combination therapy with a calcium antagonist and abeta blocker might be effective treatment for hypertensive patients with chronic renal insufficiency and left ventricular hypertrophy.

  19. Immortal time bias in pharmacoepidemiological studies on cancer patient survival: empirical illustration for beta-blocker use in four cancers with different prognosis.

    Science.gov (United States)

    Weberpals, Janick; Jansen, Lina; van Herk-Sukel, Myrthe P P; Kuiper, Josephina G; Aarts, Mieke J; Vissers, Pauline A J; Brenner, Hermann

    2017-11-01

    Immortal time bias (ITB) is still seen frequently in medical literature. However, not much is known about this bias in the field of cancer (pharmaco-)epidemiology. In context of a hypothetical beneficial beta-blocker use among cancer patients, we aimed to demonstrate the magnitude of ITB among 9876 prostate, colorectal, lung and pancreatic cancer patients diagnosed between 1998 and 2011, which were selected from a database linkage of the Netherlands Cancer Registry and the PHARMO Database Network. Hazard ratios (HR) and 95% confidence intervals from three ITB scenarios, defining exposure at a defined point after diagnosis (model 1), at any point after diagnosis (model 2) and as multiple exposures after diagnosis (model 3), were calculated to investigate the association between beta-blockers and cancer prognosis using Cox proportional hazards regression. Results were compared to unbiased estimates derived from the Mantel-Byar model. Ignoring ITB led to substantial smaller HRs for beta-blocker use proposing a significant protective association in all cancer types [e.g. HR 0.18 (0.07-0.43) for pancreatic cancer in model 1], whereas estimates derived from the Mantel-Byar model were mainly suggesting no association [e.g. HR 1.10 (0.84-1.44)]. The magnitude of bias was consistently larger among cancer types with worse prognosis [overall median HR differences between all scenarios in model 1 and Mantel-Byar model of 0.56 (prostate), 0.72 (colorectal), 0.77 (lung) and 0.85 (pancreas)]. In conclusion, ITB led to spurious beneficial associations of beta-blocker use among cancer patients. The magnitude of ITB depends on the duration of excluded immortal time and the prognosis of each cancer.

  20. Application of perfluorinated acids as ion-pairing reagents for reversed-phase chromatography and retention-hydrophobicity relationships studies of selected beta-blockers.

    Science.gov (United States)

    Flieger, J

    2010-01-22

    The addition of the homologous series of perfluorinated acids-trifluoroacetic acid (TFAA), pentafluoropropionic acid (PFPA), heptafluorobutyric acid (HFBA) to mobile phases for reversed-phase high-performance liquid chromatography (RP-HPLC) of beta-blockers was tested. Acidic modifiers were responsible for acidification of mobile phase (pH 3) ensuring the protonation of the beta-blockers and further ion pairs creation. The effect of the type and concentration of mobile phase additives on retention parameters, the efficiency of the peaks, their symmetry and separation selectivity of the beta-blockers mixture were all studied. It appeared that at increasing acid concentration, the retention factor, for all compounds investigated, increased to varying degrees. It should be stressed that the presence of acids more significantly affected the retention of the most hydrophobic beta-blockers. Differences in hydrophobicity of drugs can be maximized through variation of the hydrophobicity of additives. Thus, the relative increase in the retention depends on either concentration and hydrophobicity of the anionic mobile phase additive or hydrophobicity of analytes. According to QSRR (quantitative structure retention relationship) methodology, chromatographic lipophilicity parameters: isocratic log k and log k(w) values (extrapolated retention to pure water) were correlated with the molecular (log P(o/w)) and apparent (log P(app)) octanol-water partition coefficients obtained experimentally by countercurrent chromatography (CCC) or predicted by Pallas software. The obtained, satisfactory retention-hydrophobicity correlations indicate that, in the case of the basic drugs examined in RP-HPLC systems modified with perfluorinated acids, the retention is mainly governed by their hydrophobicity. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Producing images by ionography

    International Nuclear Information System (INIS)

    Pullan, B.R.; Dovas, T.; Mootes, B.M.

    1983-01-01

    A method and system for producing images by ionography and recording and storing same for display, comprising means for forming and recording a latent ionographic image on an electrically insulating film within a gas ionisation chamber between electrodes, scanning the latent image formed by an X-ray source, by means of an array of scanning electrodes movable on a platform to scan the latent image, the output signals from said scanning electrodes being amplified and digitised and thereafter placed in a digital storage and display device. (author)

  2. Does the prophylactic and therapeutic use of beta-blockers in preoperative patients with tetralogy of Fallot significantly prevent and treat the occurrence of cyanotic spells?

    Science.gov (United States)

    Fanous, Eliana; Mogyorósy, Gábor

    2017-10-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Does the use of beta-blockers significantly prevent and treat the occurrence of cyanotic spells in preoperative infants with tetralogy of Fallot?' Altogether, 80 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The author, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The participants in the papers reviewed were uncorrected (native or palliated) tetralogy of Fallot patients, all younger than 18 years of age, with some patients younger than 1 year. Each study reviewed included at least 10 patients, and all the studies were case series. Although even the most recent studies found were from 30 years ago, their data remain relevant. Several reviews reported either cases of overdosage or changes in efficacy of treatment after long-term usage. Four of the 6 case reviews demonstrated a decrease in the number of recurring cyanotic spells in at least 66% of the participants, following the introduction of beta-blockers. We can therefore conclude that the use of beta-blockers prevents the occurrence of cyanotic spells in preoperative patients with tetralogy of Fallot. There were insufficient data to establish optimum dosages or duration of treatment. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  3. Effects of IKur blocker MK-0448 on human right atrial action potentials from pateints in sinus rhythm and in permanent atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Simone eLoose

    2014-03-01

    Full Text Available Selective blockers of the Kv1.5 channel have been developed for the treatment of atrial fibrillation (AF, but little is known how these atrial-selective drugs affect human action potentials (APs. Therefore we have investigated the Kv1.5 blocker MK-0448 (N-{6-[(1S-1-(4-fluorophenyl-2,2-di(pyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide in right atrial trabeculae from patients in sinus rhythm (SR, permanent AF (> 6 months, and intermittent AF. MK-0448 blocked Kv1.5 current in an expression system and concentration-dependently elevated the plateau phase of atrial APs. In SR preparations stimulated at 1 Hz, MK-0448 (3 µM shortened action potential duration at 90% of repolarization (APD90 and effective refractory period (ERP, but in permanent AF preparations, MK-0448 prolonged APD90 and ERP. The effects of MK-0448 in intermittent AF resembled those in SR preparations. The APD-prolonging effect in AF preparations was more pronounced than with other IKur blockers, most likely due to the additional blocking effect of MK-0448 on IKs, a current that is present both in the atrium and ventricle. Block of IKs is probably more prominent in AF because of reduced repolarization reserve due to AF-induced remodeling.

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

    Science.gov (United States)

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

    1992-09-01

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

  5. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Shannon D Shields

    Full Text Available Cerebellar symptoms significantly diminish quality of life in patients with multiple sclerosis (MS. We previously showed that sodium channel Nav1.8, although normally restricted to peripheral somatosensory neurons, is upregulated in the cerebellum in MS, and that Nav1.8 expression is linked to ataxia and MS-like symptoms in mice. Furthermore, intracerebroventricular administration of the Nav1.8 blocker A-803467 temporarily reversed electrophysiological and behavioral manifestations of disease in a mouse MS model; unfortunately A-803467 is not orally bioavailable, diminishing the potential for translation to human patients. In the present study, we assessed the effect of per os (p.o. dosing of a new orally bioavailable Nav1.8-selective blocker, PF-01247324, in transgenic mice expressing Nav1.8 in Purkinje neurons, and in wildtype mice in the experimental autoimmune encephalomyelitis (EAE model. PF-01247324 was administered by oral gavage at 1000 mg/kg; control groups received an equal volume of vehicle. Behavioral assays of motor coordination, grip strength, and ataxia were performed. We observed significant improvements in motor coordination and cerebellar-like symptoms in mice that received PF-01247324 compared to control littermates that received vehicle. These preclinical proof-of-concept data suggest that PF-01247324, its derivatives, or other Nav1.8-selective blockers merit further study for providing symptomatic therapy for cerebellar dysfunction in MS and related disorders.

  6. Primary Colonic Angiosarcoma Seen in a Patient on Calcium Channel Blocker: A Case Report with Summary Analysis of 32 Other Cases from the Literature.

    Science.gov (United States)

    Wang, Qi; Zhao, Ting; Mi, Bian-Tao; Zhang, Yong-Lin; Wei, Rong; Tong, Hong-Lin; Wu, Maoxin

    2018-03-07

    BACKGROUND Angiosarcoma is a rare malignant mesenchymal tumor of vascular endothelial cell origin. Its occurrence in the colorectal region is extremely rare. Only 32 cases of primary colorectal angiosarcoma are reported in the current literature. Angiosarcoma in association with calcium channel blocker has been rarely reported. We present such a case of a patient who had been on levamlodipine besylate, a calcium channel blocker, for over 10 years. CASE REPORT A 53-year-old female with hypertension presented with a fever, a dry cough, and hematochezia. Computed tomography (CT) scan and angiography demonstrated a 6-cm vascular mass in the ileocecal region. The clinical symptoms stopped soon after a right hemicolectomy. The histopathology with immunohistochemical studies confirmed the diagnosis of angiosarcoma. Three months after surgery, the patient had evidence of recurrence of the tumor, however, she no longer presented with a fever or a dry cough. The patient was receiving chemotherapy at the time of the report. CONCLUSIONS Colorectal angiosarcoma is a rare malignancy of endothelial origin with uncertain etiology and often has a poor prognosis. Angiosarcoma seen in a patient taking calcium channel blocker is rare but alarming. CT scan and angiography are helpful tools to raise the suspicion of the diagnosis. A definitive pathological diagnosis relies on histopathology with immunohistochemical stains of endothelial markers. Surgical resection is still the best choice of the different treatment options.

  7. Snooker structure-based pharmacophore model explains differences in agonist and blocker binding to bitter receptor hTAS2R39.

    Directory of Open Access Journals (Sweden)

    Wibke S U Roland

    Full Text Available The human bitter taste receptor hTAS2R39 can be activated by many dietary (isoflavonoids. Furthermore, hTAS2R39 activity can be blocked by 6-methoxyflavanones, 4'-fluoro-6-methoxyflavanone in particular. A structure-based pharmacophore model of the hTAS2R39 binding pocket was built using Snooker software, which has been used successfully before for drug design of GPCRs of the rhodopsin subfamily. For the validation of the model, two sets of compounds, both of which contained actives and inactives, were used: (i an (isoflavonoid-dedicated set, and (ii a more generic, structurally diverse set. Agonists were characterized by their linear binding geometry and the fact that they bound deeply in the hTAS2R39 pocket, mapping the hydrogen donor feature based on T5.45 and N3.36, analogues of which have been proposed to play a key role in activation of GPCRs. Blockers lack hydrogen-bond donors enabling contact to the receptor. Furthermore, they had a crooked geometry, which could sterically hinder movement of the TM domains upon receptor activation. Our results reveal characteristics of hTAS2R39 agonist and bitter blocker binding, which might facilitate the development of blockers suitable to counter the bitterness of dietary hTAS2R39 agonists in food applications.

  8. Long-term effects of L- and N-type calcium channel blocker on uric acid levels and left atrial volume in hypertensive patients.

    Science.gov (United States)

    Masaki, Mitsuru; Mano, Toshiaki; Eguchi, Akiyo; Fujiwara, Shohei; Sugahara, Masataka; Hirotani, Shinichi; Tsujino, Takeshi; Komamura, Kazuo; Koshiba, Masahiro; Masuyama, Tohru

    2016-11-01

    Left ventricular (LV) diastolic dysfunction is associated with hypertension and hyperuricemia. However, it is not clear whether the L- and N-type calcium channel blocker will improve LV diastolic dysfunction through the reduction of uric acid. The aim of this study was to investigate the effects of anti-hypertensive therapy, the L- and N-type calcium channel blocker, cilnidipine or the L-type calcium channel blocker, amlodipine, on left atrial reverse remodeling and uric acid in hypertensive patients. We studied 62 patients with untreated hypertension, randomly assigned to cilnidipine or amlodipine for 48 weeks. LV diastolic function was assessed with the left atrial volume index (LAVI), mitral early diastolic wave (E), tissue Doppler early diastolic velocity (E') and the ratio (E/E'). Serum uric acid levels were measured before and after treatment. After treatment, systolic and diastolic blood pressures equally dropped in both groups. LAVI, E/E', heart rate and uric acid levels decreased at 48 weeks in the cilnidipine group but not in the amlodipine group. The % change from baseline to 48 weeks in LAVI, E wave, E/E' and uric acid levels were significantly lower in the cilnidipine group than in the amlodipine group. Larger %-drop in uric acid levels were associated with larger %-reduction of LAVI (p uric acid levels.

  9. Producing x-rays

    International Nuclear Information System (INIS)

    Mallozzi, P.J.; Epstein, H.M.; Jung, R.G.; Applebaum, D.C.; Fairand, B.P.; Gallagher, W.J.

    1977-01-01

    A method of producing x-rays by directing radiant energy from a laser onto a target is described. Conversion efficiency of at least about 3 percent is obtained by providing the radiant energy in a low-power precursor pulse of approximately uniform effective intensity focused onto the surface of the target for about 1 to 30 nanoseconds so as to generate an expanding unconfined coronal plasma having less than normal solid density throughout and comprising a low-density (underdense) region wherein the plasma frequency is less than the laser radiation frequency and a higher-density (overdense) region wherein the plasma frequency is greater than the laser radiation frequency and, about 1 to 30 nanoseconds after the precursor pulse strikes the target, a higher-power main pulse focused onto the plasma for about 10 -3 to 30 nanoseconds and having such power density and total energy that the radiant energy is absorbed in the underdense region and conducted into the overdense region to heat it and thus to produce x-rays therefrom with the plasma remaining substantially below normal solid density and thus facilitating the substantial emission of x-rays in the form of spectral lines arising from nonequilibrium ionization states

  10. Role of ascorbic acid in reduction of the incidence of the atrial fibrillation in patients under B-blocker and undergoing coronary artery bypass graft operation in early post-operative period

    Directory of Open Access Journals (Sweden)

    Moataz E. Rezk, MD

    2017-09-01

    Conclusions: The incidence of post CABG AF, intensive care unit stay, need for inotropic support and ventilator stay were decreased by patients intake of vitamin C in combination with β -blockers pre-operatively.

  11. Efficacy and Tolerability of Travoprost 0.004%/Timolol 0.5% Fixed-Dose Combination for the Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Inadequately Controlled with Beta-Blocker Monotherapy

    Science.gov (United States)

    Park, Ki Ho; Hubatsch, Douglas A.; Erichev, Valeriy; Paczka, Jose A.; Roberts, Timothy V.

    2017-01-01

    Objective. To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods. In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results. The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5 ± 2.5 mmHg and 22.2 ± 2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7 ± 3.1 mmHg and 16.1 ± 3.1 mmHg, respectively, in TTFC group and 21.1 ± 3.1 mmHg and 16.1 ± 2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (−4.6 mmHg; one-sided 95% confidence interval [−inf, −3.9]; p < 0.0001 [primary endpoint]); the upper bound of the 95% confidence interval was within the prespecified limit (<0). Both treatments were well tolerated. Conclusion. Superior IOP control was achieved with TTFC in patients with OAG or OHT previously uncontrolled with beta-blockers. No new safety findings were identified. This trial is registered with ClinicalTrials.gov NCT02003391. PMID:28239491

  12. Colorectal adenomas produce lysozyme.

    Science.gov (United States)

    Rubio, C A

    2003-01-01

    Lysozyme is an innate non-immunologic antibacterial enzyme produced by the Paneth cells of the upper intestinal tract. Lysozyme is not normally secreted in the lower intestinal tract. Previous reports indicate, however, that lysozyme may be secreted by colorectal neoplasias. The aim was to audit lysozyme expression in colorectal diseases including neoplasias. For that purpose, sections were stained with lysozyme (Muramidase), Ki67 (MIB1) and CD 68. Intense lysozyme overexpression (+++) was compared among 177 colorectal tissues: 35 having normal mucosa, 20 regenerative mucosa in inflammatory bowel disease (IBD), 2 inflammatory polyps, 3 collagenous colitis, 2 melanosis coli, 21 hyperplastic polyps, 42 tubular adenomas, 9 serrated adenomas, 30 villous adenomas and 13 invasive carcinomas. Intense lysozyme overexpression (+++) was found in 9.5% of the hyperplastic polyps, in 97.6% of the tubular adenomas, in 88.9% of the serrated adenomas, in 93.3% of the villous adenomas, in 76.9% of the carcinomas, but in none of the other tissues investigated. Neoplastic colorectal cells may acquire the capacity to produce lysozyme. The presence of that enzyme may not be a haphazard, capricious event in mutated colorectal epithelial cells but part of a more elaborate molecular behavior, not necessarily antibacterial. Recently, it was demonstrated that patients having lysozyme-secreting breast carcinomas were associated with a favorable prognosis. Whether lysozyme expression has any bearing on the biological behavior of colorectal carcinomas remains to be elucidated. Lysozyme overexpression (+++) also occurred in 2 of the 21 hyperplastic polyps, suggesting that intense lysozyme production might herald a possible dysplastic evolution in some hyperplastic polyps.

  13. A self-controlled case series to assess the effectiveness of beta blockers for heart failure in reducing hospitalisations in the elderly

    Directory of Open Access Journals (Sweden)

    Pratt Nicole L

    2011-07-01

    Full Text Available Abstract Background To determine the suitability of using the self-controlled case series design to assess improvements in health outcomes using the effectiveness of beta blockers for heart failure in reducing hospitalisations as the example. Methods The Australian Government Department of Veterans' Affairs administrative claims database was used to undertake a self-controlled case-series in elderly patients aged 65 years or over to compare the risk of a heart failure hospitalisation during periods of being exposed and unexposed to a beta blocker. Two studies, the first using a one year period and the second using a four year period were undertaken to determine if the estimates varied due to changes in severity of heart failure over time. Results In the one year period, 3,450 patients and in the four year period, 12, 682 patients had at least one hospitalisation for heart failure. The one year period showed a non-significant decrease in hospitalisations for heart failure 4-8 months after starting beta-blockers, (RR, 0.76; 95% CI (0.57-1.02 and a significant decrease in the 8-12 months post-initiation of a beta blocker for heart failure (RR, 0.62; 95% CI (0.39, 0.99. For the four year study there was an increased risk of hospitalisation less than eight months post-initiation and significant but smaller decrease in the 8-12 month window (RR, 0.90; 95% CI (0.82, 0.98. Conclusions The results of the one year observation period are similar to those observed in randomised clinical trials indicating that the self-controlled case-series method can be successfully applied to assess health outcomes. However, the result appears sensitive to the study periods used and further research to understand the appropriate applications of this method in pharmacoepidemiology is still required. The results also illustrate the benefits of extending beta blocker utilisation to the older age group of heart failure patients in which their use is common but the evidence is

  14. Effects of β-Blockers With and Without Vasodilating Properties on Central Blood Pressure: Systematic Review and Meta-Analysis of Randomized Trials in Hypertension.

    Science.gov (United States)

    Pucci, Giacomo; Ranalli, Maria Giovanna; Battista, Francesca; Schillaci, Giuseppe

    2016-02-01

    β-Blockers are less effective than other antihypertensive drug classes in reducing central systolic blood pressure (cSBP) as compared with peripheral SBP (pSBP). Whether this effect is less pronounced with vasodilating β-blockers (VBB) when compared with nonvasodilating β-blockers (NVBB) remains unsettled. We conducted a systematic review and meta-analysis of randomized trials exploring the effects of β-blockers on both pSBP and cSBP in hypertension. We selected 20 studies, for a total of 32 treatment arms (n=21 for NVBB, n=11 for VBB) and 1263 participants (n=962 for NVBB, n=301 for VBB). pSBP decreased from 150 to 133 mm Hg for NVBB and from 145 to 134 mm Hg for VBB. cSBP decreased from 137 to 126 mm Hg for NVBB and from 132 to 123 mm Hg for VBB. SBP amplification (pSBP-cSBP) decreased significantly under VBB (-5.6 mm Hg; 95% confidence interval, -7.8, -3.4 mm Hg), but not under NVBB (-1.1 mm Hg; 95% confidence interval, -3.4, +1.2 mm Hg; P<0.01 versus NVBB). There was high heterogeneity both within and between β-blockers subclasses. In a meta-regression model, the weighted difference in treatment-induced changes in SBP amplification between NVBB and VBB lost its significance after adjustment for mean age and baseline pSBP and heart rate (-2.9±2.3 mm Hg; P=0.22) and was almost abolished after adjustment for treatment-induced heart rate changes (-0.1±0.5 mm Hg; P=0.78). In conclusion, NVBBs, but not VBBs, determine a lower reduction in cSBP than in pSBP. However, the difference in treatment-induced SBP amplification changes between NVBB and VBB is nearly abolished after accounting for differences in heart rate changes. © 2015 American Heart Association, Inc.

  15. 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

  16. Effect of calcium channel blockers on gingival tissues in hypertensive patients in Lagos, Nigeria: A pilot study

    Directory of Open Access Journals (Sweden)

    Kehinde Adesola Umeizudike

    2017-01-01

    Full Text Available Background: Long-term treatment of common chronic cardiac conditions such as hypertension with calcium channel blockers (CCBs has long been associated with gingival hyperplasia. This oral side effect may affect esthetics and function, yet often overlooked and therefore underreported among Nigerians. Aim: This study aimed to determine the association of CCBs with gingival overgrowth (GO in hypertensive patients. Methods: This was a hospital-based, case–control study conducted among 116 hypertensive patients (58 CCB and 58 non-CCB age-matched controls attending the medical outpatient clinic of a tertiary health institution in Lagos, Nigeria. Data collection tools included interviewer-administered questionnaires and periodontal examination. Sociodemographic details, medical history, and periodontal indices (gingival index, plaque index, class of GO according to drug-induced GO [DIGO] Clinical Index were recorded. Results: The mean age was 59.4 ± 12.6 years, females representing 50.9%. In the CCB group, 39 (67.2% participants were on amlodipine and 19 (32.8% were on nifedipine. The mean duration of CCB use was 55.6 ± 53 months. DIGO was higher in CCB (36.2% than that in non-CCB participants (17.2% (χ2 = 4.4, P = 0.036. The risk of GO was higher in CCB users (odds ratio [OR] 2.7, [95% confidence interval (CI]: 1.1–6.5. Amlodipine users had higher DIGO (37.5% than that of nifedipine users (21.1% (OR 2.3, [95% CI]: 1.0–5.3. The predominant class of DIGO among the CCB users was Class 2 DIGO Clinical Index (90.5%. Conclusion: The study reveals that the risk of GO is nearly three times in CCB than that of non-CCB users and twice higher in amlodipine than nifedipine users in Nigeria.

  17. [Pathogenetic bases and efficacy of slow calcium channel blockers in the therapy of recurrent peptic ulcer disease associated with hypertension].

    Science.gov (United States)

    Fomina, L A; Chernin, V V

    To clarify blood calcium concentrations (BCCs) as an indicator of the functional state of the calcium-regulating system in the concomitant course of recurrent peptic ulcer disease (PUD) and hypertension, by comparing with the severity of a ulcerous process, with changes in regional microcirculation, and with the functions of the stomach. To elucidate the pathogenetic justification for and clinical efficacy of slow calcium channel blockers (SCCBs) in the treatment of this comorbidity. In the case-control study, each patient with recurrent PUD and grade 1, Stage I hypertension (Group 1; n=23) corresponded to a recurrent PUD patient matched for sex, age, and ulcer site (Group 2, n=23). The complex of treatment for these patients included the SCCB nifedipine. A control group consisted of 56 recurrent PUD patients who received combination therapy without nifedipine. All the patients over time underwent clinical and endoscopic examinations and determinations of BCCs, indicators of gastric secretory and motor functions, and regional microcirculation in the gastroduodenal mucosal biopsy specimens. Recurrent PUD was present with a reliable BCC increase that was more substantial when it was associated with hypertension. Calcium imbalance was accompanied by changes in regional microcirculation and gastric secretory and motor functional indicators forming an acid peptic factor, as well as by hypermotor dyskinesia, which were more pronounced in patients with comorbidity. Incorporation of a SCCB into a complex of therapy for recurrent PUD to eliminate the pathogenic effect of blood calcium contributed to more rapid arrest of the clinical symptoms of a recurrence, to elimination of acute-phase microcirculatory disorders in the gastroduodenal zone, and to the recovery of gastric functional indicators. Elevated blood pressure was ruled out during the therapy of concomitant diseases. Incorporation of a SCCB into the combination therapy of recurrent PUD associated with hypertension

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

    Directory of Open Access Journals (Sweden)

    Luis Rodriguez-Padial

    2017-12-01

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

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

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    Somesekhar

    2016-04-01

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

  20. Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure.

    Science.gov (United States)

    Fukui, Miho; Goda, Akiko; Komamura, Kazuo; Nakabo, Ayumi; Masaki, Mitsuru; Yoshida, Chikako; Hirotani, Shinichi; Lee-Kawabata, Masaaki; Tsujino, Takeshi; Mano, Toshiaki; Masuyama, Tohru

    2016-02-01

    While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = -0.33, p < 0.05; r = -0.28, p < 0.05, respectively), and HR (r = -0.31, p < 0.05; r = -0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction.

  1. The cholinomimetic morantel as an open channel blocker of the Ascaris suum ACR-16 nAChR.

    Science.gov (United States)

    Abongwa, Melanie; Baber, Katherine E; Martin, Richard J; Robertson, Alan P

    2016-12-01

    Nematode parasite infections pose a significant threat in human and veterinary medicine. At least a third of the world's population is at risk from nematode parasite infections. These infections not only cause health problems, but also cause loss of livestock production and hence, economic losses. Anthelmintic drugs are the mainstay by which control of nematode parasite infections is achieved. Many of the currently available anthelmintics act on nicotinic acetylcholine receptors (nAChRs). However, the detailed mode of action (MOA) of these anthelmintics is not clearly understood. Elucidation of the MOA of anthelmintics is highly desirable; an in-depth knowledge of the MOA will better inform on mechanisms of resistance development and on ways to slow down or overcome resistance. The cholinomimetic anthelmintic, morantel, has a complex MOA involving the activation and block of levamisole-sensitive single nAChR channels (L-type nAChR or L-nAChR). More recently, morantel has been demonstrated to activate Haemonchus contortus and Parascaris equorum ACR-26/ACR-27 nAChRs expressed in Xenopus laevis oocytes. Previous studies in our laboratory, however, have shown morantel does not activate the nicotine-sensitive nAChR (N-type nAChR or N-nAChR), Ascaris suum ACR-16 (Asu-ACR-16). In this study, we used two-electrode voltage-clamp (TEVC) electrophysiology to investigate the inhibitory effects of morantel, on expressed Asu-ACR-16 nAChRs in X. laevis oocytes. Our results show that morantel acts as a non-competitive antagonist on Asu-ACR-16. This non-competitive antagonism by morantel was further demonstrated to be voltage-sensitive. We conclude based on our findings that morantel is a non-competitive voltage-sensitive open channel blocker of Asu-ACR-16.

  2. BETAWIN-AHF study: effect of beta-blocker withdrawal during acute decompensation in patients with chronic heart failure.

    Science.gov (United States)

    Miró, Òscar; Müller, Christian; Martín-Sánchez, Francisco Javier; Bueno, Héctor; Mebazaa, Alexander; Herrero, Pablo; Jacob, Javier; Gil, Víctor; Escoda, Rosa; Llorens, Pere

    2016-12-01

    To evaluate the effects of discontinuing chronic beta-blocker (BB) treatment on short-term outcome in patients with chronic heart failure (CHF) during acute decompensation. We selected all the patients previously diagnosed with CHF and currently on BB and attended for acute heart failure (AHF) in one of the 35 Spanish emergency departments participating in the EAHFE registry. Patients were classified according to BB maintenance or withdrawal (BBM or BBW, respectively) during the episode. In-hospital mortality was the primary endpoint; and 30-day mortality, 30-day combined endpoint, and prolonged hospitalization were secondary. We used logistic regression for adjustment of results according to the differences between the BBM and BBW groups, and stratified analysis by age, sex, left ventricular ejection fraction, chronic obstructive pulmonary disease, heart rate (HR), and BB type (carvedilol/bisoprolol) was performed. Among 2058 patients receiving chronic BB treatment, 1990 were analyzed: BBM 530 (27 %), BBW 1460 (73 %). Compared to BBM, BBW had a higher in-hospital mortality (5.5 vs 3.0 %; p BBW and in-hospital mortality (OR 1.89; 95 % CI 1.09-3.26) and 30-day mortality (OR 2.01; 95 % CI 1.28-3.15). Stratified analysis indicated no interaction by all the subgroups analyzed, except for HR (p = 0.01 for interaction), which showed a greater negative impact of BBW in patients with HR >80 bpm (OR 2.74; 95 % CI 1.13-6.63). In the absence of clear contraindications, BB treatment should be maintained during AHF episodes in patients already receiving BB at home.

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

    Science.gov (United States)

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

    2016-09-01

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

  4. Is there any vindication for low dose nonselective β-blocker medication in patients with liver cirrhosis?

    Directory of Open Access Journals (Sweden)

    Tae Wan Kim

    2012-06-01

    Full Text Available Background/AimsNonselective β-blockers (NSBBs, such as propranolol, reportedly exert a pleiotropic effect in liver cirrhosis. A previous report suggested that survival was higher in patients receiving adjusted doses of NSBBs than in ligation patients. This study investigated whether low-dose NSBB medication has beneficial effects in patients with liver cirrhosis, especially in terms of overall survival.MethodsWe retrospectively studied 273 cirrhotic patients (199 males; age 53.6±10.2 years, mean±SD who visited our institution between March 2003 and December 2007; follow-up data were collected until June 2011. Among them, 138 patients were given a low-dose NSBB (BB group: propranolol, 20-60 mg/day, and the remaining 135 patients were not given an NSBB (NBB group. Both groups were stratified randomly according to Child-Turcotte-Pugh (CTP classification and age.ResultsThe causes of liver cirrhosis were alcohol (n=109, 39.9%, hepatitis B virus (n=125, 45.8%, hepatitis C virus (n=20, 7.3%, and cryptogenic (n=19, 7.0%. The CTP classes were distributed as follows: A, n=116, 42.5%; B, n=126, 46.2%; and C, n=31, 11.4%. Neither the overall survival (P=0.133 nor the hepatocellular carcinoma (HCC-free survival (P=0.910 differed significantly between the BB and NBB groups [probability of overall survival at 4 years: 75.1% (95% CI=67.7-82.5% and 81.2% (95% CI=74.4-88.0%, respectively; P=0.236]. In addition, the delta CTP score did not differ significantly between the two groups.ConclusionsUse of low-dose NSBB medication in patients with liver cirrhosis is not indicated in terms of overall and HCC-free survival.

  5. The Risk for Lung Cancer Incidence with Calcium Channel Blockers: A Systematic Review and Meta-Analysis of Observational Studies.

    Science.gov (United States)

    Rotshild, Victoria; Azoulay, Laurent; Zarifeh, Majd; Masarwa, Reem; Hirsh-Raccah, Bruria; Perlman, Amichai; Muszkat, Mordechai; Matok, Ilan

    2018-02-26

    There are conflicting findings regarding the association between the use of calcium channel blockers (CCBs) and the risk of lung cancer. Considering the public health importance of lung cancer prevention, and emerging evidence of a significant biologic role of calcium channel regulation in the development of lung cancer, we conducted a meta-analysis to assess the risk of lung cancer in CCB users compared with non-CCB users. We conducted a comprehensive systematic search of leading medical databases for observational studies published up to December 2017 that examined CCB use and the risk of lung cancer. We used random-effects models to pool results. The impact of duration of CCB use on the estimated effect size was explored using random effects meta-regression. Ten studies (six cohort and four case-control studies) that evaluated the overall cancer risk among 38,758 CCB users were included in the analysis. Overall risk ratio (RR) for CCB use and lung cancer was 1.15 (95% confidence interval [CI] 1.01-1.32). Subgroup analysis by duration of CCB use suggested that the observed increase in lung cancer risk was driven by the results of five studies with prolonged (≥ 4 years) exposure (RR 1.18; 95% CI 1.08-1.30). Our analysis suggests exposure to CCBs is associated with an increased risk of lung cancer. Considering their widespread use, and the paucity of data on the long-term effects of chronic exposure to CCBs, these results are reason for concern and warrant further investigation. The protocol for this study was registered at the PROSPERO registry of systematic reviews (registry number: CRD42017056362).

  6. Post-diagnostic calcium channel blocker use and breast cancer mortality: a population-based cohort study.

    Science.gov (United States)

    Busby, John; Mills, Ken; Zhang, Shu-Dong; Liberante, Fabio Giuseppe; Cardwell, Chris

    2018-02-01

    There have long been concerns that calcium channel blockers (CCBs), widely used to treat hypertension, may contribute to malignant growth through the evasion of apoptosis and proliferation of cancer cells. Worryingly, a recent cohort study found breast cancer patients who used CCBs had higher death rates, but interpreting these results was difficult as they were based on all-cause mortality and medication use before cancer diagnosis. We used UK population-based data to more robustly investigate the association between CCB use and cancer-specific mortality. We selected a cohort of patients with breast cancer newly diagnosed between 1998 and 2012 from English cancer registries. We linked to prescription and clinical records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used adjusted, time-dependent Cox-regression models to calculate hazard ratios (HRs) comparing breast cancer-specific and all-cause mortality between post-diagnostic CCB users and non-users. Our cohort included 23,669 breast cancer patients, of whom 5,141 used CCBs and 3,053 died due to their breast cancer during follow-up. After adjustment, CCB users had similar breast cancer-specific mortality to non-users (HR=0.98, 95% CI: 0.88, 1.08). There was no evidence of a dose-response relationship. We found similar associations for specific CCBs, and for all-cause mortality. In this large population-based breast cancer cohort, we did not find any evidence that CCB use is associated with increased mortality.

  7. Calcium channel blockers and breast cancer incidence: An updated systematic review and meta-analysis of the evidence.

    Science.gov (United States)

    Wright, Cameron M; Moorin, Rachael E; Chowdhury, Enayet K; Stricker, Bruno H; Reid, Christopher M; Saunders, Christobel M; Hughes, Jeffery D

    2017-10-01

    Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association would have important public health implications due to the widespread use of CCBs, this study aimed to incorporate new evidence to determine whether an association is likely to exist. We searched MEDLINE, EMBASE and the Cochrane Library to 28 June 2016 for relevant literature. References and citing articles were checked and authors contacted as necessary. Two authors independently selected articles and extracted data. Twenty-nine studies were reviewed; 26 were non-randomised studies (NRS). Meta-analysis of study data where adjustment for 'confounding by indication' was judged to be present suggests that an association, if any, is likely to be modest in magnitude (pooled odds/risk ratio 1.09 (95% confidence interval (CI) 1.03-1.15, I 2 =0%, 8 sub-studies; pooled hazard ratio 0.99 (95% CI 0.94-1.03, I 2 =35%, 9 sub-studies)). There are credible study data showing an increased relative risk with long-term use of CCBs, but the results of our meta-analysis and of meta-regression of log relative risk against minimum follow-up time are mixed. The current summative evidence does not support a clear association between taking CCBs and developing breast cancer. However, uncertainty remains, especially for long-term use and any association might not be uniform between different populations and/or breast cancer sub-types. We thus recommend further NRS in settings where CCB use is highly prevalent and population-based cancer, prescription and health-registries exist, to resolve this continuing uncertainty. PROSPERO, CRD42015026712. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Differential effects of angiotensin II receptor blocker and losartan/hydrochlorothiazide combination on central blood pressure and augmentation index.

    Science.gov (United States)

    Metoki, Hirohito; Obara, Taku; Asayama, Kei; Satoh, Michihiro; Hosaka, Miki; Elnagar, Noha; Miyawaki, Yoshinori; Kojima, Iwao; Ohkubo, Takayoshi; Imai, Yutaka

    2015-01-01

    Central systolic blood pressure (CSBP) may be a better predictor of cardiovascular risk than clinic brachial (B)SBP. The effects of dose increment from medium dose of angiotensin II receptor blockers (ARBs) to the maximum dose of ARBs (maximum) and changing from medium dose of ARBs to losartan 50 mg/hydrochlorothiazide 12.5 mg combination (combination) were compared in hypertensive patients in whom monotherapy with a medium ARB dose did not achieve goal home SBP (135 mmHg). Four weeks after treatment with a medium ARB dose monotherapy, those whose home SBP level was above 135 mmHg were randomized to receive the maximum ARB dose (n = 101) or the combination (n = 99) once daily for 8 weeks. Both regimens significantly decreased BSBP and CSBP, while a decrease in BSBP and CSBP was greater with combination. The maximum significantly decreased augmentation index (AIx), while the combination did not. The rate of a decrease in reflection to decrease in CSBP was greater in the maximum than in the combination. In the elderly subgroup, the combination more effectively lowered BSBP than the maximum, and only the combination decreased CSBP. However, in the young subgroup, the maximum decreased AIx more than combination, while both regimens lowered CSBP and BSBP to a similar extent. It is explained in part that the maximum may affect pulse wave reflection more predominantly than the combination, especially in young subjects. A weak effect on pulse wave reflection and, thus, on CSBP, of the combination may be overcome by the potent antihypertensive effect of this regimen.

  9. MANAGEMENT OF HYPERTENSION- INSIGHTS INTO REAL-WORLD CLINICAL PRACTICE FOR DIFFERENTIAL USAGE OF CALCIUM CHANNEL BLOCKERS (CCBS

    Directory of Open Access Journals (Sweden)

    Arup Dasbiswas

    2017-05-01

    Full Text Available BACKGROUND Calcium channel blockers (CCB like amlodipine, S (- amlodipine and cilnidipine, etc. have established place in the treatment of hypertension (HTN. As perceived by most of the physicians, they have comparative antihypertensive efficacy. However, available evidences suggest varied differences in incidence of pedal oedema. Aim- This survey was planned to understand real-world clinical practice pattern of Indian physicians for usage of various antihypertensive agents with emphasis on CCBs and whether differential incidence of oedema with CCBs is encountered in their clinical practice. MATERIALS AND METHODS Survey questionnaire consisting of 10 questions about preferred antihypertensive choice for different subsets of patients with HTN and efficacy and safety of S (- amlodipine was prepared and validated in small group of physicians. Overall, 494 general physicians and cardiologists practising in India were approached for seeking their opinion on usage of various CCBs. Statistical Analysis- Data were expressed in percentage. Design- Prospective, cross sectional, questionnaire-based survey. RESULTS Amongst various anti-hypertensive agents, majority of the physicians preferred CCB as their initial drug of choice for patients with HTN (53.8%, HTN with CKD (41.1%, elderly (55.3%, and young (30.8% patients. Though amlodipine was preferred by 75.7% physicians, pedal oedema was observed in >10% patients by 40.5% physicians. Most of the physicians rated S (- amlodipine to have better efficacy (79.4% and safety profile (88.3% with decreased incidence of pedal oedema than racemic Amlodipine. CONCLUSION Available evidences suggest comparative efficacy of S (- amlodipine and racemic amlodipine with varied differences in incidence of pedal oedema. However, our survey suggests better efficacy and safety of S (- amlodipine over racemic amlodipine as opined by most of the physicians of India. The survey findings need to be further evaluated in randomised

  10. Digging into Lipid Membrane Permeation for Cardiac Ion Channel Blocker d-Sotalol with All-Atom Simulations

    Directory of Open Access Journals (Sweden)

    Kevin R. DeMarco

    2018-02-01

    Full Text Available Interactions of drug molecules with lipid membranes play crucial role in their accessibility of cellular targets and can be an important predictor of their therapeutic and safety profiles. Very little is known about spatial localization of various drugs in the lipid bilayers, their active form (ionization state or translocation rates and therefore potency to bind to different sites in membrane proteins. All-atom molecular simulations may help to map drug partitioning kinetics and thermodynamics, thus providing in-depth assessment of drug lipophilicity. As a proof of principle, we evaluated extensively lipid membrane partitioning of d-sotalol, well-known blocker of a cardiac potassium channel Kv11.1 encoded by the hERG gene, with reported substantial proclivity for arrhythmogenesis. We developed the positively charged (cationic and neutral d-sotalol models, compatible with the biomolecular CHARMM force field, and subjected them to all-atom molecular dynamics (MD simulations of drug partitioning through hydrated lipid membranes, aiming to elucidate thermodynamics and kinetics of their translocation and thus putative propensities for hydrophobic and aqueous hERG access. We found that only a neutral form of d-sotalol accumulates in the membrane interior and can move across the bilayer within millisecond time scale, and can be relevant to a lipophilic channel access. The computed water-membrane partitioning coefficient for this form is in good agreement with experiment. There is a large energetic barrier for a cationic form of the drug, dominant in water, to cross the membrane, resulting in slow membrane translocation kinetics. However, this form of the drug can be important for an aqueous access pathway through the intracellular gate of hERG. This route will likely occur after a neutral form of a drug crosses the membrane and subsequently re-protonates. Our study serves to demonstrate a first step toward a framework for multi-scale in silico safety

  11. Digging into Lipid Membrane Permeation for Cardiac Ion Channel Blocker d-Sotalol with All-Atom Simulations.

    Science.gov (United States)

    DeMarco, Kevin R; Bekker, Slava; Clancy, Colleen E; Noskov, Sergei Y; Vorobyov, Igor

    2018-01-01

    Interactions of drug molecules with lipid membranes play crucial role in their accessibility of cellular targets and can be an important predictor of their therapeutic and safety profiles. Very little is known about spatial localization of various drugs in the lipid bilayers, their active form (ionization state) or translocation rates and therefore potency to bind to different sites in membrane proteins. All-atom molecular simulations may help to map drug partitioning kinetics and thermodynamics, thus providing in-depth assessment of drug lipophilicity. As a proof of principle, we evaluated extensively lipid membrane partitioning of d-sotalol, well-known blocker of a cardiac potassium channel K v 11.1 encoded by the hERG gene, with reported substantial proclivity for arrhythmogenesis. We developed the positively charged (cationic) and neutral d-sotalol models, compatible with the biomolecular CHARMM force field, and subjected them to all-atom molecular dynamics (MD) simulations of drug partitioning through hydrated lipid membranes, aiming to elucidate thermodynamics and kinetics of their translocation and thus putative propensities for hydrophobic and aqueous hERG access. We found that only a neutral form of d-sotalol accumulates in the membrane interior and can move across the bilayer within millisecond time scale, and can be relevant to a lipophilic channel access. The computed water-membrane partitioning coefficient for this form is in good agreement with experiment. There is a large energetic barrier for a cationic form of the drug, dominant in water, to cross the membrane, resulting in slow membrane translocation kinetics. However, this form of the drug can be important for an aqueous access pathway through the intracellular gate of hERG. This route will likely occur after a neutral form of a drug crosses the membrane and subsequently re-protonates. Our study serves to demonstrate a first step toward a framework for multi-scale in silico safety pharmacology

  12. Development of Producibility Evaluation Criteria

    National Research Council Canada - National Science Library

    Wilkins, Jr., James R; Kraine, Gilbert L; Thompson, Daniel H; Borchers, Kenneth H; Borchers, Marilyn M

    1993-01-01

    .... To accept this definition is to equate producibility with productivity, and normally leads to consideration of many more elements than should be taken into account for evaluating producibility...

  13. Power Producer Production Valuation

    Directory of Open Access Journals (Sweden)

    M. Kněžek

    2008-01-01

    Full Text Available The ongoing developments in the electricity market, in particular the establishment of the Prague Energy Exchange (PXE and the associated transfer from campaign-driven sale to continuous trading, represent a significant change for power companies.  Power producing companies can now optimize the sale of their production capacities with the objective of maximizing profit from wholesale electricity and supporting services. The Trading Departments measure the success rate of trading activities by the gross margin (GM, calculated by subtracting the realized sales prices from the realized purchase prices and the production cost, and indicate the profit & loss (P&L to be subsequently calculated by the Control Department. The risk management process is set up on the basis of a business strategy defining the volumes of electricity that have to be sold one year and one month before the commencement of delivery. At the same time, this process defines the volume of electricity to remain available for spot trading (trading limits. 

  14. Beta-blockers overdose

    Science.gov (United States)

    ... on how much and what type of this medicine the person took and how quickly they receive treatment. ... Aronson JK. Beta-adrenoceptor antagonists. In: Aronson JK, ed. ... Practice . 9th ed. Philadelphia, PA: Elsevier; 2018:chap 147.

  15. Brachial Plexus Blocker Prototype

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    Stéphanie Coelho Monteiro

    2017-08-01

    Full Text Available Although the area of surgical simulation has been the subject of study in recent years, it is still necessary to develop artificial experimental models with a perspective to dismiss the use of biological models. Since this makes the simulators more real, transferring the environment of the health professional to a physical or virtual reality, an anesthetic prototype has been developed, where the motor response is replicated when the brachial plexus is subjected to a proximal nervous stimulus. Using action-research techniques, with this simulator it was possible to validate that the human nerve response can be replicated, which will aid the training of health professionals, reducing possible risks in a surgical environment.

  16. Radiation produced biomaterials

    International Nuclear Information System (INIS)

    Rosiak, J.M.

    1998-01-01

    radiation technique. Immobilization of biologically active species in hydrogel matrices, their use as drug delivery systems and enzyme traps as well as modification of material surfaces to improve their biocompatibility and ability to bond antigens and antibodies have been the main subject of their investigations. The rising interest in the field of application of radiation to bioengineering was also recognized by the International Atoimc Energy Agency, which has initiated the international programs relating to those studies. In these lectures some directions of investigations on the formation of hydrogels and their applications for biomedical purposes have been specified. Also, some examples of commercialized products being produced by means of radiation technique have been presented

  17. O uso de bloqueadores neuromusculares no Brasil El uso de bloqueadores neuromusculares en Brasil Neuromuscular blockers in Brazil

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    Maria Cristina Simões de Almeida

    2004-12-01

    BNM. Las complicaciones más apuntadas fueron el bloqueo prolongado, el broncoespasmo grave y la curarización residual. CONCLUSIONES: El atracúrio es el bloqueador neuromuscular más empleado en Brasil, hay alto percentual del uso de la succinilcolina en situaciones no emergenciales, el uso de monitores de la transmisión neuromuscular es raro, y, como un corolario, un percentual significativo de uso de criterios eminentemente clínicos para considerar el paciente descurarizado. Se registró que, cerca del 30% de los anestesiologistas tuvo algún tipo de complicación consecuente del uso de eses fármacos.BACKGROUND AND OBJECTIVES: There are no statistical data on the use of neuromuscular blockers in Brazil. This study aimed at statistically analyzing this topic. METHODS: Our study has compiled 831 answers to a questionnaire filled by anesthesiologists attending the 48th Brazilian Congress of Anesthesiology in Recife, 2001, and via Internet by anesthesiologists whose e-mail addresses are in the Brazilian Society of Anesthesiology web page (www.sba.com.br. The following data were evaluated: years of experience with the specialty, region where anesthesiologists practice, neuromuscular blockers (NMB usage in order of preference, indications for succinylcholine, neuromuscular transmission monitor usage, blockade recovery criteria, neostigmine usage, NMB administration routes and description of observed complications. RESULTS: Most anesthesiologists practice for more than 11 years and the highest number of answers have come from the Southeastern region of Brazil. Most common NMB is atracurium, followed by pancuronium and succinylcholine. Succinylcholine is more frequently used for rapid sequence induction and in children (80% and 25%, respectively. Neuromuscular transmission monitors are never used by 53% of anesthesiologists, and 92% of them use clinical signs as blockade recovery criteria. Neostigmine is routinely used by 45% of professionals and 94% of them administer

  18. Role of alpha-1 blocker in expulsion of stone fragments after extracorporeal shock wave lithotripsy for renal stones

    International Nuclear Information System (INIS)

    Pirzada, A.J.; Anwar, A.; Javed, A.; Memon, I.; Mohammad, A.

    2011-01-01

    Background: Renal stone disease is a significant and worldwide health problem. Recent advances in stone management have allowed kidney stones to be treated using extracorporeal shock wave lithotripsy (ESWL), uretero-renoscopy (URS), and percutaneous nephrostolithotomy (PCNL). Recently, medical expulsion therapy (MET) has been investigated as a supplement to observation in an effort to improve spontaneous stone passage rates. Patients and Methods: This study was a randomized, controlled, prospective study to determine whether the administration of Alpha-1-adrenergic receptor antagonists as an adjunctive medical therapy, increases the efficacy of ESWL to treat renal stones. Sixty patients with renal stones of 0.5-1.5 Cm in size (average size 1.2 Cm) were included in this study underwent ESWL followed by administration of Alpha-1-adrenergic receptor antagonists at department of Urology Liaquat National Hospital Karachi from Feb 2008 to Sept 2008. This was a comparative study and patients were divided into two groups. In group A patients received conventional treatment Diclofenac sodium, Anti Spasmodic (Drotaverine HCl) as required and Proton Pump inhibitor (Omeprazole 20 mg) once daily after shock wave lithotripsy. In group B patients received alpha-1 blocker, Alfuzosin HCl 5 mg twice daily in addition to conventional treatment. All patients were instructed to drink a minimum of 2 litres water daily. Ultrasound guided Dornier Alpha Impact Lithotripter was utilised for shock wave lithotripsy. Results: Of the 60 patients, 76.7% of those receiving Alfuzosin and 46.7% of controls had achieved clinical success at 1 month (p=0.01). The mean cumulative diclofenac dose was 485 mg per patient in the Alfuzosin group and 768 mg per patient in the control group (p=0.002). This difference was statistically significant. Conclusion: Alfuzosin therapy as an adjunctive medical therapy after ESWL is more effective than lithotripsy alone for the treatment of patients with large renal

  19. 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

  20. Evaluation Effects of Verapamil as a Calcium Channel Blocker on Acquisition, Consolidation and Retrieval of Memory in Mice

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    Nooshin Masoudian

    2015-04-01

    Full Text Available Many factors are involved in learning and memory processes including brain nuclei, neurotransmitter systems, and the activity of ion channels. Studies showed inconsistent effects of calcium channel blockers on learning process, especially memory consolidation; however, little is known about their effect on memory acquisition and retrieval. Accordingly, the present study aimed to determine the effects of verapamil calcium channel antagonist as a representative of the phenylalkylamine group on different stages of memory and learning processes including acquisition, consolidation and retrieval in mice. In this experimental study, 150 male albino mice with a mean weight of 30 g were used. The mice were trained in a passive avoidance-learning task (1 mA shock for 2 seconds for evaluation of memory acquisition and consolidation and 3 seconds for evaluation of memory retrieval. The effect of verapamil (1, 2.5, 5, 10, and 20 mg/kg on memory consolidation and the most effective dose of consolidation phase on memory acquisition and retrieval was assessed. For the evaluation of memory consolidation, the animals received the drug intraperitoneally immediately after training, while for evaluation of memory acquisition and retrieval, the drug was injected one hour before training. Memory retrieval test was performed 48 hours after training (the length of time it took the animal to enter the dark part of the device. The results showed that verapamil injection exerted no effect on memory acquisition and consolidation; nevertheless, it was capable to disrupt memory retrieval in 10 and 20 mg doses. These results indicate that as a phenylalkylamine calcium channel antagonist, high doses of verapamil can im