Cardiac glycoside
Encyclopedia
Cardiac glycosides are drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

 used in the treatment of congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

 and cardiac arrhythmia. These glycoside
Glycoside
In chemistry, a glycoside is a molecule in which a sugar is bound to a non-carbohydrate moiety, usually a small organic molecule. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. These can be activated by enzyme...

s are found as secondary metabolite
Secondary metabolite
Secondary metabolites are organic compounds that are not directly involved in the normal growth, development, or reproduction of an organism. Unlike primary metabolites, absence of secondary metabolities does not result in immediate death, but rather in long-term impairment of the organism's...

s in several plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

s, but also in some animals, such as the milkweed butterflies.

Function

Therapeutic uses of cardiac glycosides primarily involve the treatment of cardiac failure. Their utility results from an increased cardiac output
Cardiac output
Cardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...

 by increasing the force of contraction
Inotrope
An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions...

. By increasing intracellular calcium as described below, cardiac glycosides increase calcium-induced calcium release
Calcium-induced calcium release
Calcium-induced calcium release is a process whereby calcium can trigger release of further calcium from the muscle sarcoplasmic reticulum. Originally proposed for skeletal muscle in the 1970s, subsequent research has revealed that it is even more pronounced in the cardiac muscle...

 and thus contraction.

Drugs such as ouabain
Ouabain
Ouabain which is also named g-strophanthin, is a poisonous cardiac glycoside.-Sources:Ouabain is found in the ripe seeds of African plants Strophanthus gratus and the bark of Acokanthera ouabaio.-Function:...

 and digoxin
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...

 are cardiac glycosides. digoxin
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...

 from the foxglove plant is used clinically, whereas ouabain
Ouabain
Ouabain which is also named g-strophanthin, is a poisonous cardiac glycoside.-Sources:Ouabain is found in the ripe seeds of African plants Strophanthus gratus and the bark of Acokanthera ouabaio.-Function:...

 is used only experimentally due to its extremely high potency.

Normally, sodium-potassium pumps
Na+/K+-ATPase
Na+/K+-ATPase is an enzyme located in the plasma membrane in all animals.- Sodium-potassium pumps :Active transport is responsible for cells containing relatively high...

 in the membrane of cells (in this case, cardiac myocytes) pump potassium ions in and sodium ions out. Cardiac glycosides inhibit this pump by stabilizing it in the E2-P transition state, so that sodium cannot be extruded: intracellular sodium concentration therefore increases. A second membrane ion exchanger, NCX, is responsible for 'pumping' calcium ions out of the cell and sodium ions in (3Na/Ca); raised intracellular sodium levels inhibit this pump, so calcium ions are not extruded and will also begin to build up inside the cell.

Increased cytoplasmic calcium concentrations cause increased calcium uptake into the sarcoplasmic reticulum via the SERCA2 transporter. Raised calcium stores in the SR allow for greater calcium release on stimulation, so the myocyte can achieve faster and more powerful contraction by cross-bridge cycling. The refractory period of the AV node is increased, so cardiac glycosides also function to regulate heart rate.

Binding of cardiac glycoside to Na-K ATPase is slow, and also, after binding, intracellular calcium increases gradually. Thus, the action of digitalis
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...

 (even on IV injection) is delayed.

Raised extracellular potassium decreases binding of cardiac glycoside to Na-K ATPase. Consequently, increased toxicity of these drugs is observed in the presence of Hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...

.

If SR calcium stores become too high, some ions are released spontaneously through SR ryanodine receptor
Ryanodine receptor
Ryanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons...

s. Then after-depolarization this effect leads initially to bigeminy: regular ectopic beats following each ventricular contraction. If higher glycoside doses are given, rhythm is lost and ventricular tachycardia ensues, followed by fibrillation.

Examples

Examples of plants producing cardiac glycosides:
  • Cardenolide
    Cardenolide
    Cardenolide is a type of steroid. Many plants contain derivatives, collectively known as cardenolides, including many in the form of cardenolide glycosides...

     type:
    • Strophanthus
      Strophanthus
      Strophanthus is a genus of 35-40 species of flowering plants in the family Apocynaceae, native mainly to tropical Africa, extending to South Africa, with a few species in Asia, from southern India to the Philippines and southern China. The name derives from the long twisted threadlike segments of...

      ouabain
      Ouabain
      Ouabain which is also named g-strophanthin, is a poisonous cardiac glycoside.-Sources:Ouabain is found in the ripe seeds of African plants Strophanthus gratus and the bark of Acokanthera ouabaio.-Function:...

       g/k/e-strophanthin
    • Digitalis
      Digitalis
      Digitalis is a genus of about 20 species of herbaceous perennials, shrubs, and biennials that are commonly called foxgloves. This genus was traditionally placed in the figwort family Scrophulariaceae, but recent reviews of phylogenetic research have placed it in the much enlarged family...

       lanata
      and Digitalis purpureadigoxin
      Digoxin
      Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...

      , digitoxin
      Digitoxin
      Digitoxin is a cardiac glycoside. It has similar structure and effects to digoxin . Unlike digoxin , it is eliminated via the liver, so could be used in patients with poor or erratic kidney function. However, it is now rarely used in current Western medical practice...

    • Nerium oleander - oleandrin
      Oleandrin
      Oleandrin is a toxic cardiac glycoside found in oleander . Along with neandrin it is primarily responsible for the toxicity of the sap of oleander...

    • Asclepias
      Asclepias
      Asclepias L. , the milkweeds, is a genus of herbaceous perennial, dicotyledonous plants that contains over 140 known species...

       sp.
  • Bufadienolide type:
    • Drimia maritima

Examples of animals producing cardiac glycosides:
  • Bufadienolide type:
    • Bufo
      Bufo
      Bufo is a large genus of about 150 species of true toads in the amphibian family Bufonidae. Bufo is a Latin word for toad.- Description :...

      toads
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