Receptor kinetics and concentration-effect relation of cardiac glycosides

Therapeutic and toxic actions of cardiac glycosides are attributed to an inhibition of Na, K-ATPase. The therapeutically relevant range is between 25% and 50% inhibition. There is a good correlation between the average steady state serum concentration of glycosides and their therapeutic action. However, therapeutic and toxic effects set in with a latency and therefore do not follow the daily variations in glycoside concentration. Although the effect follows the average serum concentrations, only the minimal concentration is measured. In principle this is only adequate if the ratio of average/minimal concentration is constant. A model calculation showed that with a constant average steady state concentration an increase in the distribution volume or a decrease in total body clearance with corresponding reduction of the daily dose lead to an increase of the minimal concentrations of 5-7%. This means a corresponding underestimation of the average concentration from the minimum concentration. However, the deviations are too small to be of clinical relevance.