Digitoxin—A Critical Review *

Within recent years, there has been an increasing interest in purified digitalis preparations. However, in spite of the original optimistic reports , the recent literature tends to discredit the value of the new preparations. Most criticisms fall into two groups: (A) Inadequacy of digitali-zation with the original recommended dosage schedules. (B) Increase in the incidence of drug toxicity. It is the purpose of this paper to analyze the value of the most commonly used purified glycoside, digitoxin. History Modern concepts of digitalis therapy began in 1785, with the publication by William Withering of his classical monograph,86 An Account of Foxglove and Some of Its Medical Uses, with Practical Remarks on Dropsy and Other Diseases. Withering, a botanist as well as a physician, recognized that the amount of active material present in the plant was not constant, and he emphasized the importance of controlling the conditions of growth of the plant and the importance of proper selection of the leaves. He cautioned against using the roots because he had observed a great variation in the potency of material obtained from that source. During most of the 19th century Withering's advice was little heeded; purple foxglove was often prescribed indiscriminately and in toxic doses. But the striking clinical results sometimes obtained with such crude preparations stimulated chemists to begin the search for active principles. The first studies recorded are those of the French chemist,Destouches, in 1808, and Quevenue and Homolle, in 1842, who probably already had digitoxin present in their digitaline preparations. In 1868, Nativelle62' 63 isolated from the dried leaves of Digitalis purpurea a relatively pure cardio-active principle, which was given the name of digitaline cristallisee, and was proved to be a potent cardiac drug by Vulpian. It has been marketed in France by the name of digitaline Nativelle. In 1875, the German chemist Schmiedeberg reported70 the isolation of a closely allied material, which he named digitoxin, and stated that it formed the bulk of digitaline cristallisee. Windaus,85 in 1926, completed the analytical investigation of digitoxin by determining its empirical formula and by interpreting its behavior on hydrolysis.