QT Prolongation and Torsade de Pointes Induced by Fluoroquinolones

QT Prolongation and Torsade de Pointes Induced by Fluoroquinolones: Infrequent Side Effects from Commonly Used Medications; Briasoulis A, Agarwal V, Pierce WJ; Cardiology 120 (2), 103-110 (Dec 2011)
Tags: ciprofloxacin gemifloxacin levofloxacin moxifloxacin ofloxacin
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Although very useful agents, fluoroquinolones are associated with a number of adverse events, some with considerable clinical significance. Prolongation of the QT interval, for example, is an adverse effect associated with the use of fluoroquinolones. Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels, especially the rapid component of the delayed rectifier potassium current I(Kr), expressed by HERG (the human ether-a-go-go-related gene). According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (TdP). Although gemifloxacin, levofloxacin, and ofloxacin are associated with a lower risk of QT prolongation compared with moxifloxacin, they should also be used with caution in patients at risk for QT prolongation. Ciprofloxacin appears to be associated with the lowest risk for QT prolongation and the lowest TdP rate. The overall risk of TdP is small with the use of fluoroquinolones. Clinicians can minimize that risk by avoiding prescriptions of multiple medications associated with QT-interval prolongation, especially in high-risk patients.

Clopidigrel besylate Vs sulfate

Antiplatelet Efficacy of Long-Term Treatment With Clopidogrel Besylate in Patients With a History of Acute Coronary Syndrome: Comparison With Clopidogrel Hydrogen Sulfate.

AuthorsTsoumani ME, et al. Show all Journal
Angiology. 2011 Dec 5. [Epub ahead of print]

Affiliation
Laboratory of Biochemistry, Department of Chemistry, School of Medicine, University of Ioannina, Ioannina, Greece.

Abstract
The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. We compared the antiplatelet effectiveness of long-term administration of the original CHS with a generic clopidogrel besylate (CB) salt formulation in 86 patients with a history of an ACS. At 1 month after the episode, patients receiving 75 mg/d CHS were randomized to continue with CHS (n = 41) or to switch to 75 mg/d CB (n = 45). Platelet aggregation, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression, and platelet-leucocyte conjugates were determined before randomization and at 6 months afterward. No difference in any platelet parameter studied was observed between the 2 groups either before randomization or after 6 months of treatment with CHS or CB. We conclude that there is no difference in the antiplatelet efficacy between CB and CHS during long-term administration in patients with a history of an ACS.

Tratamiento diabetes y enfermedad cardiovascular

By John Schieszer

DUBAI, United Arab Emirates -- December 8, 2011 -- Patients with type 2 diabetes may experience a lower incidence of cardiovascular events if they are treated with sitagliptin versus sulphonylureas, researchers said here December 5 at the International Diabetes Federation (IDF) 2011 World Diabetes Congress.

In recent years, there has been heightened concern about the potential cardiovascular risk associated with antihyperglycaemic agents used to treat type 2 diabetes. In a previously published pooled analysis of 19 clinical trials, researchers found that treatment of type 2 diabetes with sitagliptin 100 mg/day was not associated with an increased risk of cardiovascular events compared with patients not exposed to sitagliptin (0.6 vs 0.9 incident events per 100 patient-years, respectively).

Barry J. Goldstein, Merck, Sharp & Dohme Corporation, Whitehouse Station, New Jersey, and colleagues reported that sulphonylureas have potentially deleterious cellular effects in the cardiovascular system and have been shown in some clinical studies to increase the risk of cardiovascular events.

The investigators assessed cardiovascular safety by pooling 3 double-blind studies, which randomised patients at baseline to sitagliptin 100 mg/day (n = 1,226) or sulphonylureas (n = 1,225).

The trials analysed these agents when added to ongoing metformin therapy (30 weeks in duration with glimepiride) and 104 weeks (with glipizide), and the other was a monotherapy trial (104 weeks with glyburide).

In this current investigation, the researchers performed a post hoc safety analysis using custom major adverse cardiovascular events (MACE) that incorporated ischaemic events and CV deaths, without adjudication of these events.

Mean haemoglobin A1C (Hb A1C) was 7.6% and the median duration of diabetes was 5 years at baseline. Baseline characteristics were similar between groups. The cumulative patient exposure was 1,269 patient-years in the sitagliptin group and 1,274 patient-years in the sulphonylurea group.

They found that none of the patients in the sitagliptin group reported a MACE-related event, but 11 patients in the sulphonylureas group had at least 1 reported event. The incidence rate was 0 per 100 patient-years in the sitagliptin group compared with 0.9 per 100 patient-years in the sulphonylurea group.

For CV-related death, the incidence rate was 0 per 100 patient-years (0 deaths) with sitagliptin compared with 0.4 per 100 patient-years (5 deaths) with sulphonylureas.

The investigators concluded that the incidence of CV events was lower in patients treated with sitagliptin compared with sulphonylureas. They cautioned that more research is warranted and they noted the effect of sitagliptin on CV outcomes currently is being evaluated prospectively in a randomised, placebo-controlled trial.

[Presentation title: Cardiovascular Safety of Sitagliptin Versus a Sulphonylurea in Patients With Type 2 Diabetes Mellitus: A Pooled Analysis. Abstract P-1133a]

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Nitrates and Other Nitric Oxide Donors in Cardiology - Current Positioning and Perspectives

Nitrates and Other Nitric Oxide Donors in Cardiology - Current Positioning and Perspectives:

Abstract

Nitric oxide donors have been commonly used in the therapy of cardiovascular disease for more than 150 years. In spite of
this longevity and the popularity of their use, it appears somewhat paradoxical that there is no current consistent use among
cardiologists, as to both their indications and their optimal mode of administration. In part this results from their contradictory
pharmacodynamics: when given acutely, their effectiveness is undisputable; however, their long-term efficacy is potentially
limited by the development of tolerance and the induction of endothelial dysfunction, which may have negative prognostic implications.
This review reports recent biochemical and pathophysiological acquisitions, re-examines the role of nitrates and other nitric
oxide donors in cardiovascular medicine, comparing and commenting on international guidelines; and highlights areas of uncertainty,
where more clinical research with these drugs would still be warranted.

• Content Type Journal Article
• Category Review Article
• Pages 1-15
• DOI 10.1007/s10557-011-6354-0
• Authors
  
  
  • Francesco Iachini Bellisarii, Institute of Cardiology, “G. d’Annunzio” University - Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy
  • Francesco Radico, Institute of Cardiology, “G. d’Annunzio” University - Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy
  • Francesca Muscente, Institute of Cardiology, “G. d’Annunzio” University - Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy
  • John Horowitz, Department of Medicine, The Queen Elizabeth Hospital, Adelaide, Australia
  • Raffaele De Caterina, Institute of Cardiology, “G. d’Annunzio” University - Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy
  
  

• Journal Cardiovascular Drugs and Therapy
• Online ISSN 1573-7241
• Print ISSN 0920-3206