Cardiac Glycosides – The Review of Remedies in congestive heart Failure

 

R. Ramasubramania Raja1*, Y. Haribabu2, C.I. Sajeeth3

1Professor, Department of Pharmacognosy, Grace College of Pharmacy, Palakkad.

2Principal, Grace College of Pharmacy, Palakkad.

3Vice Principal, Grace College of Pharmacy, Palakkad.

*Corresponding Author E-mail: rsmr_raj@yahoo.co.in

 

ABSTRACT:

Congestive heart failure, occurs when our heart muscle doesn't pump blood as well as it must. Certain conditions, such as narrowed arteries in your heart (coronary artery disease) or high blood pressure, gradually leave your heart too weak or stiff to fill and pump efficiently. Herbal drugs like digitalis, squill, and stropanthus commonly find the treatment of heart diseases. Caridio active glycosides like having the purpurea glycosides A and B present in the herb of digitalis, glucoscillaren A and scillarenase having the squill and strophanthus having strophanthoside.

 

KEYWORDS: Heart failure, Digitalis, Squill, Strophanthus, strophanthoside.

 

 


INTRODUCTION:

Heart failure is a progressive disease that is characterized by a gradual reduction in cardiac performance coronary artery disease and hypertension are most common cause of heart failure.

 

Acute Treatment

Chronic Treatment

Diuretics

Diuretics

Aldosterone receptor antagonist

Vasodilators

Angiotensin converting enzyme inhibitors

Beta agonist

Angiotensin receptor blockers

Bipyridines

Beta blockers

Natriuretic peptide

Cardiac glycosides

Left ventricular assist device

Vasodilators

 

 

Cardiac glycosides:

They are defined as naturally occurring drugs whose actions include both beneficial and toxic effects on the heart.

 

Uses:

During past, they are used to assassinate people, as arrow poisons etc., To treat congestive heart failure (dropsy). For treatment of arterial fibrillation and flutter.

 

History:

These glycosides are also named as sterols. Chemically, aglycone part of cardiac glycosides is a steroidal moiety. They are either C23 or C24 steroids because of either 5 membered or 6 membered lactone ring respectively. Those with 5 membered ring are called cardenolides, while with 6 membered ring are termed as bufadienolides. (1)

 

Cardenolides

Bufadienolides

No. of carbons-23

24

No. of double bonds- one double bond attached to steroidal nucleus through C17 position

Lacton3 ring contains 2 double bonds- and attached to steroidal nucleus by 17 beta position

Families- leguminosae, sterculiaceae, cruciferae, scrophulariaceae., Euphorbiaceae

 

Lilliaceae, raninculaceae.

Example- convallariamajlis (Lily of the valley), digitalis lanata

Leonidas cardiac (mother wart), drinks maritima(squill)

 

Natural sources containing cardiac glycosides:

Digitalis, Squill, Strophanthus and Oleander

 

Digitalis (1,5)

Synonym- digitalis leaves, fox glove leaves.

Biological source- Digitalis purpura, Digitalis lanata

Family-Scrophulariaceae

Dried at a temperature below 60, immediately after collecting leaves, the leaves should contain not more than 5% of moisture.

 

Morphological features:

colour- dark grayish green

Odour- slight

Taste- bitter

Size- 10-40 cm long, 4-20 cm wide

 

Shape:

ovate lanceolate to broadly ovate, with irregularly crenate or serrate or occasionally dentate margin. Leaves are pubescent with pennate venation and prominent veinlets on under surface. Generally the leaves are broken and crumpled.

 

Microscopic features:

Digitalis is a dorsi ventral leaf. It has anomocytic stomata on both surfaces and water pores at the apex of most marginal teeth. Trichomes are uniseriate, multicellular and bluntly point. There are also glandular trichomes with unicellular stalk and unicellular or bicellularhead. Glandular trichomes are generally located over the veins. Collapsed celled trichome is an important characteristic of digitalis. Starch grains are present in endodermis. Collenchymas at 3 different places, i.e., at upper epidermis, lower epidermis, and pericyclic part, which is also a characteristic to digitalis.(10)

 

Constituents:

Digitalis contains 0.2to 0.45% mixture of both 1°&2° cardiac glycosides. Primary glycosides are less absorbed and less stable than secondary glycosides such as digitoxin, gitoxin and gitaloxin. Primary glycosides are purpurea glycosides A&B and glucogitaloxan. Purpurea glycoside A on enzymatic hydrolysis yields digitoxin and glucose molecules. On further reaction, it produces digitoxigenin and 3 glucose molecules. Purpurea glycoside B on enzymatic hydrolysis gives gitoxin and glucose, further produces gitoxigenin and 3 digitoxose. It also contain 2 saponin glycosides namely, Digitonin and gitonin.(5)

 

Chemical Tests

Keller-kiliani test:-

The chemical test consists of boiling about 1g finely powdered digitalis with 10ml of 70% alcohol for 2-3 minutes. Extract is filtered 5 ml of water is added along with 0.5 ml strong solution of lead acetate. Shake well & separate the filtrate. Clear filtrate is treated with equal volume of chloroform and evaporated to yeild the extractive. The extractive is dissolved in glacial acetic acid. After cooling, 2 drops ferric chloride solution is added. These contents are transferred to a test tube containing 2 ml concentrated sulphuricacid. A reddish brown layer acquiring bluish - green colorafter standing is observed due to the presence of digitoxose.

 

Legal test: -

The extract is dissolved in pyridine, sodium nitro pruside solution is added to it and made alkaline pink.

 

Baljet test:-

To a section of digitalis, sodium picrate solution is added. It shows yellow to orange color.

 

Allied drugs:

Digitalis lanata have following synonyms like Wolly fox glove leaf, Austrial digitalis.

 

Biological source:

It is dried leaves of Digitalis lanata Ehrhart.

 

Family:

Scrophulariaceae.

It contains majorly 5 constituents. They are: Lantanosides A, B, C, D & E. Here, glycone digitoxose is acetylated.

 

Uses:

Irregular heart rhythms (atrial fibrillation), Congestive heart failure (CHF), Asthma, Epilepsy Tuberculosis, Constipation.

 

Squill (2)

Synonym:-Sea onion, scilla, Janglipyaj.

 

Biological source:-

Obtained from dried slices of bulbs of Urgenia indica kunth.

 

European squill is obtained from Urginea maritima.

 

Morphological features:-

Colour: -The slices of squill bulbs are slightly yellowish to white.

 

Odour: - Slight and characteristic.

Taste: - Bitter, mucilaginous and 3to 8mm broad.

The slices of Indian squill are united in group of 4 to 8. Which are curved? In case of European squill, it contains concavo-convex slices,3-6cm in length and 4-8mm in width. It is hygroscopic in nature. The transverse section shows presence of polygonal axially elongated epidermis, parenchymatous mucilage nous mesophyll with raphides of calcium oxalate crystals and is interrapted by small vascular bundles. In case of European squill polygonal cells are present with very rare encountering of stomach. Mesophyll is charecterised by mucilage present in large polygonal parenchymatouscells. Mesophyll also shows raphides of calcium oxalate.

 

Chemical Constituents:

Indian squill contains about 0.3% of cardiac glycosides. It yields to alcohol about 20 to 40% of extractive. Others are mucilage and calcium oxalate. Scillaren A and B are major glycosides. The drug also contains glucoscillaren A and scillarenase. In case of European squill, it contains the same along with proscillaridin A, xanthoscillide, flavonoids, mucilage sinistrin (carbohydrate similar to insulin). (6)

 

Chemical tests:

Mesophy ll strains with alkaline colarinsolution to red colour If treated with 0.1M iodine solutiom, it obtains reddish purple colour.

 

Uses: -

Coronary heart disease (CHD): Early research suggests that injecting methylproscillaridin, a chemical in squill, intravenously (by IV) might improve heart function in people with coronary heart disease. Abnormal heart rhythm and other heart problems. Fluid retention (edema). Bronchitis. Asthma. Whooping cough. Thinning mucus. Inducing vomiting. Other conditions.

 

Strophanthus (1,3)

Synonym: - Semino strophanthi.

Biological source:-

These are dried ripe seeds of strophanthus kombe oiver or strophanthus hispidus De Candolle

 

Family: - Apocyanaceae.

 

Morphological features:-

These seeds are obtained from fruits with 2 follicles. Seeds arev10-20mm in length, 3-5mm width and 2mm thickness. Shape is lanceolate. Silky touch of seeds is due to trichomes. Endosperm and embryo is quite oily in nature. When treated with 80% sulphuric acid, the endosperm shows deep emerald green colour. The seeds have bitter taste and unpleasant odour.

 

Constituents:-

Drug contains mixture of glycosides called k-strophanthene. It contains k-strophanthoside, k- strophanthoside beta- cymarin and cymarol. Except cymarol, all the 3 glycosides yeildstrophanthidin on hydrolysis. K- strophanthoside is considered as main glycoside which on hydrolysis gives aglycone strophanthidine along with 3 sugars cymarose, alpha and beta -glucose.(7)

Chemical tests:-

Glycosides show green colour on addition of sulphuric acid.

 

Uses:

Hardening of the arteries” (arteriosclerosis). Heart problems. High blood pressure. Other conditions. More evidence is needed to rate the effectiveness of strophanthus for these uses.

 

Toxicity of cardiac glycosides: (4, 8)

From ancient times, humans have used cardiac-glycoside-containing plants and their crude extracts as arrow coatings, homicidal or suicidal aids, rat poisons, heart tonics, diuretics and emetics, primarily due to the toxic nature of these compounds. Thus, though cardiac glycosides have been used for their medicinal function, their toxicity must also be recognized. For example, in 2008 US poison centers reported 2,632 cases of digoxin toxicity, and 17 cases of digoxin-related deaths. Because cardiac glycosides affect the cardiovascular, neurologic, and gastrointestinal systems, these three systems can be used to determine the effects of toxicity. The effect of these compounds on the cardiovascular system presents a reason for concern, as they can directly affect the function of the heart through their inotropic and chronotropic effects. In terms of inotropic activity, excessive cardiac glycoside dosage results in cardiac contractions with greater force, as further calcium is released from the SR of cardiac muscle cells. Toxicity also results in changes to heart chronotropic activity, resulting in multiple kinds of dysrhythmia and potentially fatal ventricular tachycardia. These dysrhythmias are an effect of an influx of sodium and decrease of resting membrane potential threshold in cardiac muscle cells. When taken beyond a narrow dosage range specific to each particular cardiac glycoside, these compounds can rapidly become dangerous. In sum, they interfere with fundamental processes that regulate membrane potential. They are toxic to the heart, the brain, and the gut at doses that are not difficult to reach. In the heart, the most common negative effect is premature ventricular contraction.(6,7,9)

 

CONCLUSION:

The herbal drugs like digitalis, squill, and strophanthus is very potential drug for the treatment of cardiac failure. Digitalis is a ornamental plant but its have the high value of cardiac glycosides. The squill and stophanthus involved the congestive heart failure, the isolated glycoside based drug is once formulated it will very useful for this society. India is growing country once its formulations over it is reaches the economic poor people also.

 

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8.        Moses Kandula, Karthika. P, Robin Abraham. Nurses Action towards Cardio Vascular Emergencies Asian Journal of Nursing Education and Research .10.5958/2349-2996.2019.00024.7

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Received on 21.04.2021         Modified on 10.06.2021

Accepted on 08.07.2021       ©A&V Publications All right reserved

Res. J. Pharmacognosy and Phytochem. 2021; 13(4):187-190.

DOI: 10.52711/0975-4385.2021.00032