Cardiac Glycosides.ppt 5th sem.ppt

Cardiac glycosides

2. Drugs having the cardiac ionotropic
property increase in force of contraction
of heart muscles.
They increase the myocardial contractility and
improves cardiac output without proportionate
increase in Oxygen consumption
Do not increase the heart rate.
Digitalis is the genus name for the family
of the plants that provide most of the
medically useful cardiac glycosides -
Digoxin

3. Cardenolides and Bufadienolides
Digitalis purpurea –Digitoxin, Gitoxin and
Gitalin
Digitalis lanata -Digitoxin, Gitoxin and
Digoxin
Strophanthus gratus –Ouabin
Thevetia nerifolia –Thevetin
Convallaria majalis –Convallotoxin
Bufo vulgris -Bufotoxin

4. Digitalis purpurea Digitalis lanata
Strophanthus gratus

5. Urginea maritima Thevetia
nerifolia
Convallaria majalis

6. AllCardiacglycosides
aglycone(genin)part
(activepharmacologically)
sugar(glucoseordigitoxose)
attachedatCarbon3of
nucleus
Aglycone:Steroidring
(cyclopentanoperhydrophena
nthrenering)andlactone
ringattachedat17
th
position

7. Cardio-active Glycosides
•Group of steroidal glycosides act as cardiotonic agent.
•They increase tone, excitability and contractility of
cardiac muscles.
General properties of Cardiac Glycosides :
Amorphous powder
Bitter taste
Solubility in H2O
Insolubility in Organic solvents
Very toxic compounds
Odorless
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8. Solubility:
Glycosides are soluble in water and alcohols.
Increase number of sugars increase water solubility.
Aglycones soluble in CHCl
3and EtOAc.
Stability:
Acid hydrolysis:
Split sugars from the aglycone first.
Enzymatic hydrolysis:
Split sugars stepwise starting from the terminal sugar.
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9. Acts on Failing Heart:
Inability of the heart to pump sufficient blood to meet
the metabolic demands of the body
Reduced efficiency of the heart as a pump

10. According to their therapeutic effects:
CHF(congestive heart failure) and cardiac muscle
stimulators such as:
Digitalis glycosides: digoxin, digitoxin, gitoxin
(Fox glove leaves).
Ouabain: Strophanthus gratus seeds.
K-strophanthin: Strophanthus kombe seeds.
Scillaren A,B which isolated from red and white
Squill bulbs.
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11. According to the type of lactone ring:
1. Cardenolide(one double bond, lactone ring) :
Has five member lactone ring (unsaturated) attached at C17 B position
of steroidal nucleus.
Examples:
Digitalis glycosides:
Digoxin
Digitoxin
Gitoxin
Strophanthus gratus glycoside :
Oubain
Strophanthus Kombe glycoside :
K-strophanthin
2. Bufadienolide:(contain two double bonds, lactone ring):
Has six member ( unsaturated ) lactone ring attached at C-17 alpha –
position
Example:
Squill bulb glycoside
Scillaren
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12. Nomenclature :
The cardiac glycosides occur mainly in plants from which the
names have been derived.
Digitalis purpurea,
Digitalis lanata,
Strophanthus kombe are the major sources of the
cardiac glycosides.
Aglycone moiety:
The term 'genin' at the end refers to only the aglycone
portion (without the sugar).
The aglycone portion of cardiac glycosides is more
important than the glycone portion.
Aglycone part has steroidal nucleus
(cyclopentanoperhudrophenanthrene)
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13. Sugar moiety(glycone) :
The glycosides usually contain 3 to 4 sugars attached at C-3
OH.
The sugars most commonly used include L-rhamnose, D-
glucose, D-digitoxose, D-digitalose, D-digginose.
Beside Glucose and Rhamnose they usually contain
deoxysugars.
These sugars predominantly exist in the cardiac glycosides in
the β-conformation.
Digitoxose Digitose
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14. STRUCTURE:
These are composed of two structural features :
the sugar (glycone) moiety and
the non-sugar (aglycone -steroid) moieties.
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15. The R group at the 17-position defines the class of cardiac
glycoside.
Two classes have been observed in Nature:
1.cardenolides and
2.bufadienolides .
The cardenolides have an unsaturated butyrolactone ring
While the bufadienolides have an a-pyrone ring.
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16. Steroidal nucleus must be present.
3b-OH group involved in glycosidic linkage.
14b-OH group at C-14.
A/B ring junction cis
B/C ring junction trans
C/D ring junction cis
Additional oH groups at C-5, C-11 and C-16 may be
present.
The presence of lactone ring
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17. 17

18. Scrophulariaceae family:
foxglove -biennial flowering plants
cases of poisoning rare
natural emetic if eaten in excess
Digitalis purpurealeaf –purple, British
Digitalis Tablets B.P.
Tincture of Digitalis B.P.
commercially grown Holland, E. Europe
Digitalis lanataleaf –white,
Mediterranean
used for manufacture of pure glycosides
i.e. digoxin, lanatoside C
commericially produced Holland, Equador, USA
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19. Digitalisconsists of the
dried leaves of Digitalis
purpurea.
It is required to contain
at least 0.3% of total
cardinolides calculated
as digitoxin.
Parts Used: Leaves
Habitat:Native to
Western Europe.
Although the plant is
cultivated, wild plants
are thought to be
superior.
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20. Glycosides
purpurea glycoside A
purpurea glycoside B
Glucogitaloxin
Steroid cardenolides
contains 30 glycosides, 6 main ones
At C-3 of the genin: a linear chain of 3 digitoxose sugar
moieties terminated by glucose.
On drying: enzyme degradation takes place loss of the terminal
glucose. Produces
Digitoxin
Gitoxin
Gitaloxin
also contains anthraquinone glycosides
Saponins
Sopogenins
Flavonoids
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21. compounds belong to
cardenolide series
5 membered lactone ring
approx 96 compounds
[1930-1950 Stroll
worked on structures]
R
1
R
2
Names 1
y
2
y
H H digitoxigeninAAdigitoxin
H OH gitoxigeninBBgitoxin
OHH digoxigeninCCdigoxin
OHOH diginatigeninDDdiginatin
H formylestergitaloxigeninEEgitaloxin
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*
* Acetyl group
confers crystalline
properties -makes
compounds more
easily isolated

22. Some cardioactive glycosides from D.lanata:
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23. sugar found on primary glycosides of D.lanata.
glucose on the end of a chain of O-linked digitoxose
sugars at C
3.
expect about 10 compounds from D.lanata
important ones:
Digoxin “Lanoxin” –Wellcome –0.25 μg white tablet
Digitoxin “Digitalin” 0.25 μg small pink tablet
Lanatoside “Cedilanid” 0.10 μg –less well absorbed but
used for rapid digitalisation
Others not marketed, used experimentally 23

24. They are Cardiotonics used to treat Congestive heart
failure(CHF).
They increase force of contraction of cardiac muscles without
increase oxygen consumption.
Increase cardiac output.
The diastolic phase last longer so decrease heart rate.
Have diuretic effect due to increase amount of blood passing
through the kidney.
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25. General test for steroids:
Liebermann’s test:
Glycoside in acetic anhydride + Few drops of conc. H
2SO
4
Reddish violet Green
Test for Deoxysugars:
Keller-Kiliani’s Test:
Glycoside in acetic anhydride containing traces of FeCl
3+
conc. H
2SO
4 on the wall of the tube
Acetic acid layer acquire Bluish-green colour (Digitalis)
Acetic acid layer acquire Red colour (Squill)
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26. Test for 5-membered lactone ring:
Legal’s test:
Cardenolide in pyridine + Na nitroprusside + NaOH
deep redcolour.
Kedde’s test:
Cardenolide+ 3,5 dinitrobenzoic acid (Kedde’s reagent A)
+ NaOH (Kedde’s reagent B) violet colour.
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