Cardiac glycosides, toxicities and therapeutic options in modern medicine.
Glycosides are composed of the interaction of nucleotides like glucose (sugar) in our nature. Sometimes they are called O-glycosides, S-glycosides. C-glycosides, N-glycoside,s and so on on the basis of their principle molecule. O-glycosides are the most common glycosides found in our nature. There is a linkage called Glycosidic Linkage between glycone and aglycone. Basically, polysaccharides are the broad-based definition of glycosides. Glycosides are found in Aloe, Rhubarb, Senna, poplar, willow and so on. There are different types of glycosides like phenol glycosides, aldehyde glycoside, isothiocynate steroidal glycoside, etc. Steroidal glycosides are called cardiac glycosides. They are used as cardiotonic. There are some drugs that use as therapeutic medicine such as Digitalis, Ouabain, Thevatia, Indian Squill, etc. But they have toxicities. They have some separate activities such as electrophysiological and mechanical on the the heart. Again they inhibit sodium-potassium adenosine in heart. If sodium potassium ATPase concentration decreased, there will be a chance of human the heart failure. This is the adverse effect of cardiac glycosides.
Cardiac
Glycosides:
Cardiac glycosides are called steroid
glycosides. There are some plants that contain C23 or C24 they
are steroidal glycosides that show the effect of slow or fast heart rating.
There are lots of plants but Digitalis
purpuria is the most successful plant to treat cardiac disease. Basically,
Glycosides are confined in nature. There are two types of genin here which use
as cardiotonic. They are Cardenolide and Bufadienolide.
Image: Cardenolides Image: Bufadienolide
Cardenolides are five-membered rings and
bufadienolides are six-membered rings. Cardenolides are found numerously than
bufadienoli. Again, there are different types of sugar found in cardiac
glycosides. They are fucose, rhamnose, digitalose, cymarose, glucose, thevetose,
and so on.
There are some characteristics of cardiac
glycosides. They are:
1. Generally they found originally in a plant
but some of them result from removal of one sugar molecule from another primary
glycoside such as Digitalis.
2. Cardiac glycosides are non-volatile.
3.They are soluble in water and organic
solvent.
4. They are generally bitter in taste.
5. They are solid either crystalline or
amorphous.
Not only Digitalis purpurea but also different types of the plant contain
cardenolide derivatives. There are some constituents of plants and their parts.
1.
Digitalis Leaf: In this portion purpurea glycosides A and
purpurea glycosides B are found and they possess the C3 genin in
digitoxoses sugar moieties. The most active components in Digitalis leaf are
gitoxin and digitoxin.
Image: Digitalis Leaf
2. Digitalis seeds:
The seeds of Digitalis purpurea have
more different types of glycosides linkage from Digitalis leaves. After
extraction from seeds, they are called Digitalin. They are composed of gitonin,
saponins digitonin, and digitalium verum which is water-soluble.
Image: Digitalis seeds
3. Digitalis Lanata Leaf:
They are identical to Digitalis purpurea but
the main different thing is that they are acetylated at digitoxose moiety to
the last glucose moiety. They are crystalline.
Cardiac
Glycosides Toxicities:
Cardiac glycosides basically reversibly
inhibit sodium-potassium ATPase exchanger and increased intracellular calcium
and inotropy. But the thing is cardiac glycosides have a low level of the
therapeutic effect. Cardiac glycosides are used as medicine for treating
cardiac disease. Sometimes it became poisonous or toxicity because of overdose
by accidental or intentional ingestion. The symptoms of overdose are nausea,
vomiting, and abdominal pain. But the main life-threatening condition is
cardiac toxicities. There are a different types of cardiac glycosides which
have different variation of their pharmacological and pharmacokinetic
properties in their structure. Nerium oleander seeds composed of cardiac
glycosides including thevetin A, thevetin B, and neriifolin. If anyone takes
about five to fifteen nerium leaves it would result in fatal poisoning. Even
one leaf of Nerium oleander could be created toxicity in children. Not only
leaves but also extract, flowers, and root extract can cause more nonfatal
cases. In the case of taking of eight to ten leaves of Thevetia peruviana seeds
can be fatal to but the seeds have not been shown to correlate with the degree
of toxicity of glycosides.
The main mechanism of cardiac glycoside toxicities is that cardiac glycosides bind to inactive the sodium-potassium ATPase that emits sodium and implies potassium into cardiomyocytes or myocardiocytes which are the cells that made make up the heart muscle. The inhibition causes a build-up of intracellular sodium that helps to increase intracellular calcium in this channel. It turns persuades further calcium ion release from the sarcoplasmic reticulum (SR) which main function is to store calcium ion. After then, it increased the force of contraction of the heart. When intracellular calcium ions increase then it also raises the membrane potential of the cell and conducting increasing rates of spontaneous cellular depolarization. The myocardium becomes irritable and increased vagal tone that causes bradycardia. This inhibition of the sodium-potassium ATPase also causes of hyperkalemia. In the case of acute poisoning by these alkaloids, the degree of hyperkalemia can cause severe toxicity.
Therapeutic
Options in Modern Medicine:
There are different types of drugs that
have a therapeutic effect on cardiac disease.
Name of the drug |
Biological Source |
Active Constituents |
Uses |
Digitalis |
Dried leaves of Digitalis purpurea |
Purpurea glycoside A and B. |
Cardiotonic. |
European Squill |
Dried sliced bulb of Urginea maratima |
Scillaren A & B |
Cardiotonic. |
Ouabain |
Dried seeds of Strophanthus gratus |
Ouabin |
Cardiotonic. |
Thevetia |
Dried seeds of Thevetia nerifolia |
Thevetin |
Cardiotonic. |
Indian Squill |
Dried sliced bulb of Urginea indica |
Scillaren A & B |
Cardiotonic. |
Digitalis (Digitalis purpurea) components have different uses in medical science.
They are used in the treatment of chronic heart failure because they have the
most successful cardiotonic effect than other glycoside plants. At present
there are various modern and more efficacious treatments for heart failure
disease are available. This digitalis compounds are very convenient and widely
used. In the case of heart failure patients, they have shown a great result for
digoxin in clinical studies. They are used in conjunction with vasodilators and
diuretics that improves the cardiac output and ejection fraction that reduces
pulmonary capillary pressure. It helps to reduce pulmonary congestion and edema
(swelling). For this reason, heart rate changes very little. These drugs help
to increases the inotropy rate. Another main important function of digitalis of
digoxin is it works on blood vessels is vasoconstriction (narrow of the blood
vessel), given to heart failure patients and the systemic vascular resistance
falls. This mechanism helps to development of cardiac output that leads to withdrawal
of compensatory vasoconstrictor mechanisms. The Digitalis compounds have a
small direct diuretic effect on the kidneys that is beneficial to heart failure
patients.
References:
1. https://www.tandfonline.com/doi/abs/10.1081/CLT-120022006
4. https://www.uspharmacist.com/article/digoxin-use-in-modern-medicine
5. https://www.researchgate.net/publication/308548495_CARDIAC_GLYCOSIDES_USES_IN_HEART
Thank you for the info
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