Importance of serum glycoside concentrations
For drug-mediated therapy it was a great advance when dose-related response could be replaced by correlating blood level and effect. The various factors, which related to the dose could influence the blood level, the concentration at the site of effect and finally the intensity of effect, are shown in Table 1. From this synopsis it could be deduced that for digitalis glycosides some of these factors are well-known. The absorption rate of digitoxin is 100%, for digoxin 80% and more. It is not advisable to administer drugs with a lower absorption rate. The distribution volume is also known. For the closely protein-bound digitoxin (protein binding 92–97%), it is about 0.5–0.71/kg body weight and for digoxin with a protein binding of 25% about 6–101/kg body weight, thus for a patient of 70 kg body weight resulting in a distribution volume for digitoxin of 51 and for digoxin of about 500–6001 respectively. Even metabolic passage and speed of elimination are well known. While digitoxin with a half-life of approximately 200 hours is mainly metabolized, digoxin is almost totally excreted via the kidney. In contrast, the significance and quantitative extent of those factors which are able to influence the concentration of glycosides at the site of action are far less known. Best studied and documented by empirical observations is the importance of pathological conditions on the intensity of effect. Here the synergism of hypokalemia and hypercalcemia and vice versa should be mentioned. The increased sensitivity for glycosides in hypoxemia is well known, especially in cor pulmonale as well as in prolonged severe heart failure, but also in hypothyroidism.
KeywordsToxicity Fibril Glycoside Digoxin Hypothyroidism
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