THE SCOPE OF ANTIARRHYTHMIC DRUGS AND THE PROSPECTS FOR THE USE OF HIGHLY EFFECTIVE ANTIARRHYTHMIC DRUGS
Abstract
Cardiac arrhythmias remain a common cause of death and disability. Antiarrhythmic drugs (AADs) and antiarrhythmic agents remain a cornerstone of current cardiac arrhythmia management, despite moderate efficacy and the potential for significant adverse proarrhythmic effects. Due to conceptual, regulatory and financial considerations, the number of novel antiarrhythmic targets and agents in the development pipeline has decreased substantially during the last few decades. However, several promising candidates remain and there are exciting developments in repurposing and reformulating already existing drugs for indications related to cardiac arrhythmias. Due to the multifactorial intracardiac and extracardiac causes of Atrial fibrillation (AF) generation, current development of anti-AF agents is concentrated on modulation of ion channel activity as well as upstream therapies that reduce structural substrates. AF is a growing clinical problem associated with increased morbidity and mortality. While currently available antiarrhythmic drugs (AADs) are highly effective in acute cardioversion of paroxysmal AF, they are generally only moderately successful in maintaining sinus rhythm over the long-term maintenance. When taking into account both safety and efficacy, the existing results suggest that multiple ion channel blockers that show strong suppression of peak INa with comparatively quick unbinding kinetics, as well as inhibition of late INa and IKr, may be better for the treatment of AF. This review highlights the potential for therapeutic repurposing, reviews new compounds and formulations now undergoing clinical development for rhythm management of atrial fibrillation, and addresses the important conceptual factors for the creation of new antiarrhythmic drugs. Lastly, prospective paths for AAD advancement are examined. These elements, when combined with a growing knowledge of the molecular mechanisms behind cardiac arrhythmias, provide a cautiously optimistic prognosis for better pharmacological therapy options for cardiac arrhythmia patients.
Keywords
Cardiac ion currents, proarrhythmic causes, antiarrhythmic drugs, antiarrhythmic tactics, and cardiac arrhythmias.How to Cite
References
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