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Sex and Gender Aspects in Antiarrhythmic Therapy

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Sex and Gender Differences in Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 214))

Abstract

Although cardiac arrhythmia had long been considered a predominantly male syndrome, it is now clear that arrhythmia is also a primary cause of mortality in women. Notably, the manifestation of specific arrhythmia syndromes appears to be gender specific. In particular, female sex is an independent risk factor for development of torsade de pointes (TdP) arrhythmias not only in congenital long QT syndromes but also in acquired long QT syndromes which occur as adverse effects of existing drugs. Males, on the other hand, are more likely to develop Brugada syndrome. Recent clinical and experimental studies suggest that these differences may stem from intrinsic sex differences in cardiac tissue. These include fundamental electrical differences resulting from variable ion channel expression and diverse sex hormonal regulation via long-term genomic and acute nongenomic pathways, and sex differences in drug responses and metabolisms. Undoubtedly, determining the effect of gender on cardiac function will be difficult and require sophisticated methodologies. However, gender differences underlying predilection to distinct arrhythmia syndromes must be revealed so that new therapeutic strategies that take gender into account can be applied to at-risk patients.

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Abbreviations

TdP:

Torsade de pointe(s)

ECG:

Electrocardiograms

QTC :

Rate-corrected QT

ER:

Estrogen receptor

MAPK:

Mitogen-activated protein kinase

eNOS:

Endothelial nitric oxide synthase

PI3K:

Phosphoinositide 3-kinase

IKs :

The slow delayed rectifier K+ current

ICa,L :

L-type Ca2+ current

hERG:

Human ether-a-go-go-related gene

IKr :

The rapid delayed rectifier current

E2:

17β-estradiol

WPW:

Wolff–Parkinson–White

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Authors and Affiliations

  1. Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Junko Kurokawa PhD, Masami Kodama & Tetsushi Furukawa

  2. Department of Pharmacology, University of California, Davis, CA, USA

    Colleen E. Clancy

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  1. Junko Kurokawa PhD
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  2. Masami Kodama
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  3. Tetsushi Furukawa
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  4. Colleen E. Clancy
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Correspondence to Junko Kurokawa PhD .

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Editors and Affiliations

  1. Institute of Gender in Medicine (GiM), Center for Cardiovascular Research (CCR), Charité - Universitätsmedizin Berlin, Hessische Str. 3-4, Berlin, 10115, Germany

    Vera Regitz-Zagrosek

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Kurokawa, J., Kodama, M., Furukawa, T., Clancy, C.E. (2013). Sex and Gender Aspects in Antiarrhythmic Therapy. In: Regitz-Zagrosek, V. (eds) Sex and Gender Differences in Pharmacology. Handbook of Experimental Pharmacology, vol 214. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30726-3_12

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