Mechanisms of action of antiarrhythmic drugs: from ion channel blockage to arrhythmia termination.
Over the past decade, the strategies for arrhythmia management have been in transition. Physical methods to treat arrhythmias, such as ICDs and RF ablation, have undergone considerable refinement and wider application. Ischemic heart disease and congestive heart failure have been identified as clinical situations in which antiarrhythmic drugs have a significant proarrhythmic potential. However, drugs retain an important role in arrhythmia management. Strategies to mitigate the structural and functional changes that occur in hypertrophy, ischemia, and infarction have not been thoroughly explored. Membrane ion channels and receptors are the targets for the action of currently available drugs. The cloning and sequencing of these ion channels and receptors should improve the efficacy and specificity of drug design. Cardiac Na+, Ca2+, K+, and nonspecific cation channels have a clearly defined role in the generation of the normal action potential. Their specific roles in the various clinical arrhythmias is less certain. There are sufficient data to associate specific ionic channels with normal and abnormal automaticity and with reentry occurring in specific regions of the heart. A rational choice of antiarrthymic drugs can be made when an arrhythmogenic mechanism and the putative underlying membrane currents can be identified based on the clinical characteristics of the arrhythmia. For a majority of clinical arrhythmias, this ideal has not been achieved. When a particular drug is used to treat an arrhythmia, the full complement of its actions will depend on which multiple ion channels or receptors are blocked and the kinetics of drug interaction with these sites.
Duke Scholars
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Related Subject Headings
- Myocardium
- Ion Channels
- Ion Channel Gating
- Humans
- Cardiovascular System & Hematology
- Arrhythmias, Cardiac
- Anti-Arrhythmia Agents
- 3202 Clinical sciences
- 3201 Cardiovascular medicine and haematology
- 1103 Clinical Sciences
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Myocardium
- Ion Channels
- Ion Channel Gating
- Humans
- Cardiovascular System & Hematology
- Arrhythmias, Cardiac
- Anti-Arrhythmia Agents
- 3202 Clinical sciences
- 3201 Cardiovascular medicine and haematology
- 1103 Clinical Sciences