PubMed · 3543680
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J W Mason. 1987-02-19. Amiodarone.. https://doi.org/10.1056/nejm198702193160807
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Amiodarone is widely used in heart diseases but also provokes severe adverse effects due to its accumulation in other tissues than the heart. In order to circumvent side effects colloidal drug carriers have been designed to deliver the drug specifically to the site of action. Many preparation methods have been described and most have been reported to involve a high initial drug loss when introduced in an aqueous environment. Lipid nanocapsules (LNC) were prepared by a new phase inversion procedure and characterized in terms of size, surface potential, encapsulation efficiency, and drug release pattern. The encapsulation rate was varying between 92 and 94%. LNC did not display a distinct initial burst effect while the drug release of amiodarone can be prolonged over a significant period. Acceptor phase interfaces such as liposomes or blank LNC were applied to the release medium to enable a drug release to larger extents. The release was triggered by the pH of the release medium showing a faster release for lower pH; t(50%) values vary from 25.6 h (pH 2) to 236.3 h (pH 7.4). Moreover, LNC were prepared of different sizes (24.7+/-2.0 to 102.5+/-0.9 nm) showing only slight influences on their drug release profiles. It was concluded that the LNC surface is able to retain amphiphilic drugs. Such properties could allow drug delivery to the site of action without high initial drug loss.
Atrial fibrillation (AF) is a common contributor to cardiovascular morbidity and mortality. Two generally acceptable strategies exist for long-term AF management, with ongoing studies comparing the overall mortality associated with each. One strategy aims to maintain sinus rhythm, with antiarrhythmic agents if necessary, thereby preserving physiological cardiac electrical function but exposing the patient to the potential side effects of potent drugs. The second approach is to control the ventricular rate and prevent thromboembolic complications with anticoagulants, leaving the patient with AF. Both beta-blocking agents and calcium antagonists are more effective than digoxin in achieving rate control. Several nonpharmacological therapies including catheter ablation, implantable devices and surgical interventions show promise for rate control and maintenance of sinus rhythm. This paper provides an overview of new developments in pharmacological and nonpharmacological therapy. Key features of recently published clinical guidelines, including a unified classification scheme for AF and issues relating to rate control and maintenance of sinus rhythm, are considered. In addition, preliminary results from the recently presented AFFIRM study, the largest AF trial to date, are summarized. Finally, we discuss recent insights into the basic mechanisms underlying AF that have potentially significant clinical implications.
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