tailieunhanh - Antiarrhythmic Drugs A practical guide – Part 6

Dược lý lâm sàng dược lý lâm sàng của amiodarone có thể được khá mô tả như là kỳ lạ, phức tạp, và không đầy đủ hiểu. Sau một liều uống, 30-50% được hấp thụ từ đường tiêu hóa. Sau khi hấp thụ, amiodarone hiển thị một mô hình phức tạp của phân phối thường được mô tả như là một mô hình (ít nhất) ba ngăn. | 90 Chapter 5 of calcium-channel blockade a Class IV effect . All these effects can produce antiarrhythmic actions. Clinical pharmacology The clinical pharmacology of amiodarone can be fairly described as being bizarre complex and incompletely understood. After an oral dose 30-50 is absorbed from the gastrointestinal tract. Once absorbed amiodarone displays a complex pattern of distribution that is usually described as at least a three-compartment model. The first or central compartment is thought to consist of the intravascular space. With aggressive loading regimens the central compartment can be largely saturated within 24 hours. The second or peripheral compartment probably consists of most of the body s organs. It is thought to take 5-7 days to begin to saturate the peripheral compartment by use of a typical regimen for loading amiodarone an important consideration because the antiarrhythmic effects of amiodarone are thought to require adequate filling of this peripheral compartment. The third or deep compartment consists of the body s fat. It takes many weeks or months for the third compartment to become saturated and it may never actually become completely saturated. Because of the depth of this deep compartment amiodarone has a huge volume of distribution many times the body s actual volume it has been calculated to be as high as 500 L. Tissue concentrations of amiodarone vary markedly from organ to organ and are the highest in organs with high-fat content such as the liver and the lungs. In vivo amiodarone is in a state of equilibrium among the three compartments. If the drug is discontinued the concentration of amiodarone in the central compartment the serum falls quickly to low levels but the low serum levels persist for weeks or months because of the slow leaching of the drug from the peripheral and deep compartments. Amiodarone is metabolized in the liver to desethylamiodarone DEA which displays electrophysiologic effects similar to the parent compound