Nomenclature : The cardiac glycosides occur mainly in plants from which the names have been derived. Reduced contraction of heart leads to reduced heart output but new blood keeps coming in resulting in the increase in heart blood volume. The size and degree of unsaturation varies with the source of the glycoside. These additional hydroxyl groups influence the partitioning of the cardiac glycosides into the aqueous media and greatly affect the duration of action. Cardiac steroids are widely used in the modern treatment of congestive heart failure and for treatment of atrial fibrillation and flutter. The aglycone moiety: The steroid nucleus has a unique set of fused ring system that makes the aglycone moiety structurally distinct from the other more common steroid ring systems. Saponins on hydrolysis yield an aglycone known as "sapogenin". The mechanism whereby cardiac glycosides cause a positive inotropic effect and electrophysiologic changes is still not completely clear. The so-called NEUTRAL saponins are derivatives of STEROIDS with spiroketal side chains. The lactone ring is not absolutely required. The bufadienolides derived their name from the genetic name for the toad, Bufo (the prototype compound bufalin was isolated from the skin of toads). Here the aglycone is a flavonoid. For example, the glycone and aglycone portions can be chemically separated by hydrolysis in the presence of acid. 3-Beta-D-(monoglucuronyl)18-beta-glycyrrhetinic acid, a metabolite of glycyrrhetinic acid inhibits 11-beta-hydroxysteroid dehydrogenase which converts ACTIVE cortisol to INACTIVE cortisone in the kidneys. On membrane depolarization sodium fluxes-in leading to an immediate elevation of the action potential. A deep red colour is produced.
Elevated intracellular calcium concentration triggers a series of intracellular biochemical events that ultimately result in an increase in the force of the myocardial contraction or a positive inotropic effect.
G- glycoside : The aglycone portion (figure below) of cardiac glycosides is more important than the glycone portion.
Here the aglycone is a simple phenolic structure. In the body, toxic substances are often bonded to glucuronic acid to increase their water solubility; the resulting glucuronides are then excreted. Expectorants are used to decrease the viscosity of tenacious mucus, or to increase the secretion of mucus in dry irritant unproductive cough, thereby, lubricating the air passages and making coughing more productive. An example of these is amygdalin from almonds. The Koenigs-Knorr reaction is the condensation of glycosyl halides and alcohols in the presence of metal salts such as silver carbonate or mercuric oxide. Some enzymes such as α-amylase can only hydrolize α-linkages; others, such as emulsin, can only affect β-linkages.
Saturation of the lactone ring dramatically reduced the biological activity. Salicin is converted in the body into salicylic acid, which is closely related to aspirin and has analgesic, antipyretic and antiinflammatory effects. Cardiac glycosides are proposed to inhibit this enzyme with a net result of reduced sodium exchange with potassium that leaves increased intracellular Na+.