Pulmonary Delivery of Antiarrhythmic Drugs for Rapid Conversion of New-Onset Atrial Fibrillation
Autor: | Richard L. Verrier, Luiz Belardinelli |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Invited Review Article Drug Compounding medicine.medical_treatment pulmonary delivery dominant frequency 030204 cardiovascular system & hematology Flecainide Acetate Cardioversion 03 medical and health sciences QRS complex 0302 clinical medicine cardioversion Heart Rate Internal medicine Administration Inhalation Atrial Fibrillation medicine Animals Humans Adverse effect Flecainide Metoprolol Pharmacology Inhalation business.industry Nebulizers and Vaporizers Atrial fibrillation medicine.disease Disease Models Animal Treatment Outcome 030104 developmental biology cyclodextrin Cardiology Cardiology and Cardiovascular Medicine business Anti-Arrhythmia Agents medicine.drug |
Zdroj: | Journal of Cardiovascular Pharmacology |
ISSN: | 0160-2446 |
Popis: | Pharmacologic management of atrial fibrillation (AF) is a pressing problem. This arrhythmia afflicts >5 million individuals in the United States and prevalence is estimated to rise to 12 million by 2050. Although the pill-in-the-pocket regimen for self-administered AF cardioversion introduced over a decade ago has proven useful, significant drawbacks exist. Among these are the relatively long latency of effects in the range of hours along with potential for hypotension and other adverse effects. This experience prompted development of a new strategy for increasing plasma concentrations of antiarrhythmic drugs rapidly and for a limited time, namely, pulmonary delivery. In preclinical studies in Yorkshire pigs, intratracheal administration of flecainide was shown to cause a rapid, reproducible increase in plasma drug levels. Moreover, pulmonary delivery of flecainide converted AF to normal sinus rhythm by prolonging atrial depolarization, which slows intra-atrial conduction and seems to be directly correlated with efficacy in converting AF. The rapid rise in plasma flecainide levels optimizes its anti-AF effects while minimizing adverse influences on ventricular depolarization and contractility. A more concentrated and soluble formulation of flecainide using a novel cyclodextrin complex excipient reduced net drug delivery for AF conversion when compared to the acetate formulation. Inhalation of the beta-adrenergic blocking agent metoprolol slows ventricular rate and can also terminate AF. In human subjects, oral inhalation of flecainide acetate with a hand-held, breath-actuated nebulizer results in signature prolongation of the QRS complex without serious adverse events. Thus, pulmonary delivery is a promising advance in pharmacologic approach to management of AF. |
Databáze: | OpenAIRE |
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