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Cardiac glycoside: Wikis


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Cardiac glycosides are drugs used in the treatment of congestive heart failure and cardiac arrhythmia. These glycosides are found as secondary metabolites in several plants, but also in some animals.

Example of the chemical structure of one of the cardiac glycosides.


Cardiac glycosides are used therapeutically mainly in the treatment of cardiac failure, due to their anti-arrhythmic effects. These are caused by the ability to increase cardiac output by increasing force of contraction by prolonging the plateau phase of cardiac depolarization thus slowing ventricular contraction and allowing more time for ventricular filling. (If you increase the pre-load, you increase the force of contraction - Frank-Starling law). Drugs such as ouabain and digoxin commonly used clinically and experimentally.

Normally, sodium-potassium pumps 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 pump, NCX, is responsible for pumping calcium ions out of the cell and sodium ions in (3Na/Ca); raised intracellular sodium levels inhibit this exchange, 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.

If SR calcium stores become too high, some ions are released spontaneously through SR ryanodine receptors. 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 of plants producing cardiac glycosides:

Examples of animals producing cardiac glycosides:

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