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The narrow therapeutic margin can be explained by the mechanism of action. Cardiac glycosides (CG) bind to the extracellular side of Na+/K+-ATPases of cardiomyocytes and inhibit enzyme activity. The Na+/K+-ATPases operate to pump out Na+ leaked into the cell and to retrieve K+ leaked from the cell.
The FeIII-P450-RH binary complex is first reduced by NADPH, then forms the ternary complex, O2-FeII-P450-RH, which accepts a second electron and finally disintegrates into FeIII-P450, one equivalent of H2O, and hydroxylated drug (R-OH). |
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