[Cardiac glycosides: From ancient history through Withering's foxglove to endogeneous cardiac glycosides].

Abstract

For centuries, drugs that increase the power of contraction of the failing heart have been used for the treatment of congestive heart failure (dropsy). The cardiac effect is due to the content of cardiac glycosides. Squill or sea onion, Urginea (Scilla) maritima, a seashore plant, was known by the ancient Romans and Syrians and possibly also by the ancient Egyptians. Squills were used erratically, but some prescriptions indicate that they may have been used for the treatment of oedematous states. The toxic effect of strophanthus species was known from poisoned arrows used by the natives in Africa. Digitalis, derived form the foxglove plant, Digitalis purpurea, is mentioned in writings as early as 1250; a Welsh family, known as the Physicians of Myddvai, collected different herbs and digitalis was included in their prescriptions. However, the druge was used erratically until the 18th century, when William Withering, an English physician and botanist, published a monograph describing the clinical effects of an extract of the foxglove plant. Later, in 1785, the indication and the toxicity of digitalis were reported in his book, "An account of the Foxglove and some of its medical uses with practical remarks on dropsy, and other diseases". In Denmark, the leaves of Digitalis purpurea or Digitalis lanata were tested for cardiac glycoside activity. The standardized digitalis powder was used in tinctures, infusions, and tablets. The preparations were included in successive editions of the Danish pharmacopoeia, some of the tinctures already in 1828, i.e. before the standardization of the drug. Isolation of cardiac glycosides from digitalis, strophanthus and squill and determination of their chemical structures initiated biochemical and pharmacological studies. The scientific advances led to an understanding of cardiac muscle contractility and the Na,K pump as the cellular receptor for the inotropic action of digitalis. Examination of putative endogenous ligands to the receptor revealed some endogenous cardiac glycosides of similar or identical structures as those found in digitalis, strophanthus and squill. Increased concentrations of these glycosides are found in patients with heart failure. Further investigations are needed to determine whether the secretion of glycosides might be a physiologic response to a diminished cardiac output.