Cardioactive or Cardiotonic or Cardiac Glycosides

These glycosides are used therapeutically to strengthen the weakened heart. These thus allow the heart to function more efficiently. These compounds have the ability to increase the force of systolic contraction and shortening the period of systole thus giving the heart more time to rest between contractions.

The therapeutic efficiency of cardiac glycoside depends both upon the chemical nature of aglycone and the type and no. of sugar to which it is attached. The aglycones have steroidal skeleton, which is closely related to Vit-D, bile acid, or sex hormones. The sugar part renders the comp. More soluble and increases the power of fixation of glycoside to heart muscle. Two types of aglycones can be distinguished depending upon whether there is 5-membered or 6-membered lactone is attached

Cardenolide: -

Present in digitalis and strophanthus.

Bufadienolide: -

It is present in white squill.

R = C₆H₁₁O₅ (Cardenolide & Bufadienolide)

R = H in Cardenolide it is Digitoxigenin

Digitalis: -

B.O. :- Digitalis purpurea

Digitalis lanata

FAMILY :- Scrophulariaceae

P.U. :- Dried Leaves

Habitat:-

The plants are biennial or perennial herbs. Digitalis purpurea is indigenous to central and south-eastern Europe. Cultivated in Holland, Germany, France, Australia and U.S.A.

Digitalis lanata is also indigenous to central and south-eastern Europe and cultivated in Holland, U.S.A and Aqua Dor.

Collection & Drying: -

Leaves are collected in June from 2^nd year of growth of plant before opening of flower. Immediately dried artificially at 60⁰C. Dried leaves should not contain more than 5% of moisture.

Digitalis purpurea leaves Digitalis lanata leaves

Ovate or oblong Sessile without petiole

Petiole winged Oblong lanceolate

Dentate margin Linear lanceolate

10 cm Straight margin, entire margin

Upto 40 cm 4 cm – 35 cm

Digitalis Glycosides:-

There are four types of glycosides.

Digitoxigenin

Gitoxigenin

Gitaloxigenin

Digoxigenin

First three types are present in D. purpurea and D. lanata, while the last group of glycosides (Digoxigenin) is present only in D. lanata.

Derivatives of Digitoxigenin

Digitalis purpurea Digitalis lanata

Digitoxin Acetyl Digitoxin

The sugar chain contains This contains three molecules of

3 molecules of digitoxose. digitoxose and one acetyl group.

Purpurea Glycoside A Lanotosie A

This comp. Contains This glycoside contains 3 digitoxose

3 molecules of digitoxose units, one acetyl group,

and one mol. of glucose one glucose molecule.

Digitoxin: -

Digitoxin is a chief constituent of D. purpurea. 1 mg of digitoxin is therapeutically equivalent 1 g of digitalis leaves. It is completely absorbed through G.I.T. Therefore in equivalent or I.V. doses produce essentially same therapeutic effects and the drug has similar onset of action by either route.

Onset of action after I.V. injection is ½ to 2 hours with maximum effect occurring at 8 – 9 hours later. Following oral administration onset occur at 2 – 4 hours with maximum effect occurring at 12 – 24 hours.

The chief disadvantage of Digitoxin is its slow onset of action and prolonged half life, when compared with digoxin which is the active constituent of D. lanata. These constituents (Acetyl Digitoxin lanatoside A) are properly absorbed from G.I.T, so are rarely used.

Derivatives of Gitoxigenin: -

Digitalis purpurea Digitalis lanata

Gitoxin Lanatoside B

This glycoside contains three

digitoxose units, one acetyl group

and one glucose molecule.

Glucogitoxin or Purpurea glycoside B

This contains 3 digitoxose and

one glucose molecule.

Derivatives of Gitaloxigenin: -

Digitalis purpurea Digitalis lanata

Gitaloxin Lanatoside E

This glycoside contains three

digitoxose, one acetyl

and one glucose.

Derivatives of Digoxigenin

All these derivatives are found in D. lanata

1. Digoxin (3-Diqitoxose)

2. Acetyl digoxin (3-diqitoxose+1-Acetyl)

3. lanatoside C (3-diqitoxose+1acetyl+1-glucase)

4. Deslanoside (3-digitoxose+1-glucose)

Digoxin

Digoxin is chief constituent of D. lanata. It is the drug of choice in the treatment of congestive heart failure for following reasons.

1. Rapid onset of Action: -

Onset of action occurs in 5-30min. Following the I.V injection with somewhat longer when drug is administered orally. Maximum, effect occurring at 2-4 hours, depending upon the route through which drug is administered. Drug is completely eliminated with 2-6 days. The biologic half-life of digoxin is 18 hours.

2. It has relatively short duration of action, which minimize the chance of digitalis intoxication.

3. It can be administered orally as well as IV and I. M.

Deslanoside

Deslanoside is a derivative of lanatoside c and is given in left side heart failure. Onset of action occurs at 10-30min. With maximum effect occurring at 2-5 hours.

All digitalis glycosides possess same qualitative effect on heart, peripheral vascular system, C.N.S and GIT. But they vary in potency, rate of absorption, onset of action and rate of elimination.

In sufficient doses they produce nausea and vomiting b/c of their direct effect on CNS. Other toxic effects, which occur slowly, include drowsiness, marked confusion particularly in old age patients’ visual disturbances and disturbances of cardiac rhythm i.e. premature ventricular contraction.

Gitalin

Gitalin is a mixture of

(i) Gitoxin 13-14%

(ii) Gitaloxin 13-14%

(iii) Digitoxin 14-20%

Adulterants Of digitalis

It has three adulterants available in literature.

Verbascum Leaves (Mullein leaves)

These can easily be distinguished from the standard drug by the presence of numerous branched veins.

Leaves of Salvia Spp:-

These can be easily distinguished from shape. The cordate shape and long petiole while digitalis purpurea had rounded shape.

Leaves of Digitalis Thapsi: -

(i) These do not contain glandular trichome D. purpurea contain glandular and non-glandular trichome.

(ii) Colour of D. thapsi leaves is dark yellowish green while that of standard drug is grayish green.

(iii) Prisms of Ca-oxalate are present in D. thapsi while absent in case of standard drug.

Strophanthus

B.O. Strophanthus kombe

Strophanthus hispidus.

Family Apocynaceae

P.U. Dried ripened seeds.

Habitat

Strophanthus kombe is indigenous to forests of eastern Africa and yield a commercial variety of seeds known as green strophanthus. Strophanthus hispidus is indigenous to the forest of West Africa and yield a commercial variety of seeds known as brown seeds strophanthus.

Collection and Drying

The fruits are collected in Tune and July when they are fully ripened. Epicarp and mesocarp are removed and seeds are dried in endocarp.

Green Strophanthus is considered to be the best since it contains high conc. of strophanthus.

The seeds of St. kombe are lanceolated while that of St. hispidus is spindle shaped.

Constituents: -

The endosperm of seeds contains in addition to aleurone grains, strophanthin, fixed oil 30%.

Other constituents are two nitrogenous base trigonelline and choline. The seeds also contain resin and mucilages. Seeds have a spike odour, very bitter taste. The active constituent Strophanthin is soluble in water and dil. Alcohol. It is insoluble in chloroform ether and benzene.

Uses

Cardiotonic

Diuretic

Structure: -

Histochemical test: -

Section of seeds + drops of 67% H₂SO₄ the cells of endosperm containing strophanthine will resume green colour i.e. in the case of St. kombe and St. hispidus.

White Squill

It consists of white flesh inner scales of the bulb of white variety of Urginea maritima.

Family Liliaceae

Habitat These are found in France, Greece, Spain, Algeria, and Morocco.

Collection and Drying: -

The bulbs are collected late in August the outer membranous scales are removed. The inner fleshly scales are cut into small pieces and dried artificially, or in sun. the drug has slight odour and bitter taste.

Constituents: -

Squill contains a principal glycoside Scillaren that on hydrolysis yields aglycone; scillarenin and sugars.

Structure: -

Uses: -

Cardioactive

Diuretic

Expectorant

Emetic