CARDIAC GLYCOSIDES SEMINAR.pptx

INTRODUCTION
What are Glycosides?
Glycosides may be defined as the organic compounds from plants or animal
sources which on enzymatic or acid hydrolysis give one or more sugar moieties
along with non sugar moiety.
Cardiac Glycosides :
Cardiac glycosides are an important class of naturally occurring drugs
having cardiac inotropic property which has, both, toxic as well as
beneficial effects on the heart.

SCROPHULARIAC
EAE
Example
Digitalis purpurea
APOCYANACEAE
Example
Strophanthus hispidus
LILIACEAE
Example
Urginea indica
Sources of Cardiac
Glycosides

General Properties of Cardiac
Glycosides
● Amorphous powder
● Bitter taste
● Odourless
● Soluble in water and alcohols
● Insoluble in Organic solvents
● Highly toxic in nature

HISTORICAL USE
Extracted from the skin of Poison Toad
Used as poison to
Assassinate people and to make
poisonous arrows.
MODERN USE
Extracted from Plant Glycosides
To treat congestive heart failure.
Treatment of atrial fibrillation and flutter.

GENERAL
MEACHANSIM OF
ACTION FOR
CARDIAC
GLYCOSIDES
Direct inhibition of Na+/K+‐ATPase
Inability of myocytes to pump Na+ leading to
intracellular accumulation of Na+
Indirect inhibition of Na+/ Ca++ exchanger,
which increases intracellular Ca++
More Ca++ released by the
sarcoplasmic reticulum, thereby making more
Ca++ available to bind to troponin-C
Increased force and velocity of
contraction
Topic Features
Describe here the topic of the
section

CLASSIFICATI
ON
According to the type of
Lactone Ring

o Contains a five membered lactone ring
with one double bond.
o The lactone ring is attached to steroidal
nucleus through C-17 position.
o Present in a large no. in nature.
o Examples : Digitoxin, Digoxin
CARDENOLI
DE
BUFADIENOLI
DE
o Contains a six membered lactone ring
with two double bonds.
o The lactone ring is attached to steroidal
nucleus through 17ᵝ position.
o Occurrence is fewer in nature.
o Examples : Bufalin, Scillaren

CHEMISTRY OF CARDIAC
GLYCOSIDES

GLYCONE
MOIETY
● 3-4 Sugar molecules attached to aglycone moiety.
● Sugar attached to 3rd position through b linkage
● Various types of sugars such as L-Rhamnose, D-
Glucose, D-Fructose, D-Digitoxose, D-Digitalose,
D-Cymarose, D-Sarmentose , D-Thevatose, L-
Vallarose etc.
● Glycone moiety does not potentiates the medicinal
activity, but it increases the solubilization of
aglycone part in the body and it is beneficial in the
absorption as well as distribution.
● Sugars predominantly exist as B conformation.
● Besides Glucose and Rhamnose they usually
contain De-oxysugars.
● Presence of -CH3CO group on sugar affects
lipophilic and kinetics of entire glycosides

AGLYCONE
MOIETY
o The term “genin” is used for aglycone moiety
without sugar.
o Steroidal nucleus is important for the activity.
o 3B-OH group is attached to the sugar moiety.
o 14B-OH group is important for activity.
o Additional -OH groups at C-5 , C-11, C-16 may be
present.
o 17B-OH is attached to the unsaturated lactone.
o No. of -OH groups increases on aglycone, it
makes onset of action faster as well as it
enhances metabolism.
o Cis A/B, Trans B/C, Cis C/D are present in the
structure. It makes nucleus very stable so more
active.
o Presence and attachment to a specific position to
a steroidal nucleus of lactone is essential for
proper activity.
o Size and degree of unsaturation varies with
source of glycoside.
o Aglycone moiety more important than Glycone
moiety.
Cyclopentanoperhydrophenth
rene
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19

LACTONE
MOIETY
● The presence of Unsaturated lactone
increases activity of Cardiac glycosides,
but if it is saturated then it will lose its
activity.
PYRONE
Butyrolacton
e
Cardenolide Bufadienolide
Butyrolactone ring Pyrone ring
It has a C-23
Steroidal nucleus
It has a C-24
Steroidal nucleus
Found in
Leguminosae,
Cruciferae,
Euphorbiaceae
Found in Liliaceae,
Ranunculeasae
Example :
Digitalis,
Strophanthus
Example : Squill

Chemical Tests for Cardiac
Glycosides
Drug 50% ethanol and 0.1 ml 1%
solution of m- dinitrobenzene
in ethanol
+ +
Violet colour appears due to presence
of active methylene group
Raymond’s Test :
2-3 drops of 20%
sodium hydroxide
solution

Glycosides
Crude
drug
Heat with 0.1 -5% solution of
xanthydrol in glacial acetic
acid
+ +
Red Colour is produced due to
presence of 2-deoxy sugar
Xanthydrol Test :
1% Hydrochloric acid

Glycosides
Glycosid
e
Mixture of 1% ferric sulphate
solution in 5% glacial acetic
acid
+ +
Reddish Brown colour appears at the
junction and the upper liquid layer is
Bluish-Green due to presence of
deoxy sugar
Keller-Killiani test :
1-2 drops of
concentrated sulphuric
acid

Glycosides
Glycosid
e
Few drops of Pyridine
+ +
Appearance of a Silver Mirror shows
positive test
Tollen’s test : (silver mirror test)
Few ml of Tollen’s Reagent
(solution of silver nitrate and
ammonia)

Glycosides
Drug
extracted
with CHCl3
Few drops of acetic
anhydride
+ +
Appearance of Violet ring which turns
Blue and finally Green due to
presence of sterol
Liebermann Test For Sterols :
Concentrated Sulphuric
acid (from side wall of
test tube)

Glycosides
Piece of lamina or thick
section of leaf
+
Yellow To Orange is seen
Baljet Test :
Sodium picrate reagent

Glycosides
Solution of Glycosides +
Development of Blue or Violet colour that fades out
in 1-2 hours shows presence of cardenolides
Kedde Test :
Kedde reagent
(equal volumes of 2% 3,5
dinitrobenzoic acid in menthol and
7.5% aqueous solution of KOH)

Glycosides
Drug Few ml of pyridine and 2
drops of nitroprusside
+ +
Deep Red colour is produced
Legal Test :
2-3 drops of 20%
sodium hydroxide
solution

Glycosides
Solution of Glycosides +
Appearance of Blue or Violet colour that shows
presence of cardenolides and bufadienolides
Antimony trichloride Test :
Solution of antimony tetrachloride
and trichloroacetic acid and heat

PLANTS CONTAINING
CARDIAC GLYCOSIDES
Digitalis purpurea
Digitalis lanata
Urginea maritima
Urginea indica

Synonym : Purple foxglove, Lady’s glove,
Finger flower
Biological source : Dried leaves of
Digitalis purpurea.
Family : Scrophulariaceae
● Shape : Ovate lanceolate to
broadly ovate
● Colour : Dark greyish green
● Odour : Odourless
● Taste : Bitter
● Size : 30cm long, 4cm wide
● Leaves : Hairy, slightly pubescent
on both surfaces.
● Margin : Crenate or serrate or
dentate
● Apex : Sub acute
DIGITALIS
PURPUREA
MORPHOLOGY

GEOGRAPHICAL SOURCES DIGITALIS
PURPUREA
USA
INDIA
ENGLAND OTHER PARTS
OF EUROPE
IRAQ
MEXICO
JAPAN

1. Biennial herb (a plant which blooms in its second year and then dies)
2. Good quality of drug is obtained especially from cultivated plant.
3. Flourish best in well drained loose soil preferably of siliceous origin with some slight
shade
4. Plant growing in sunny situation possesses the active qualities of herb
compare to shade by trees
5. Best grown when allowed to seed itself.
6. Seeds should be mixed with fine sand in order to ensure even distribution.
7. Before sowing soil is sterilized.
8. Sown in spring, the plant does not blossom till the following year.
CULTIVATION OF DIGITALIS
PURPUREA

9. In dry season, sufficient water is supplied.
10. In 1st year, long stalk with rosette of leaves is produced.
11. True plant shows dull pink or magenta not pale colored or spotted externally.
PURPUREA

COLLECTION OF DIGITALIS
PURPUREA
1. September to November by hand Collection
2. Organic matter and discolored leaves are avoided.
3. After collection, leaves should be dried as soon as possible at 60°C.
4. By quick drying, green color of leaves is maintained.
5. Drying is carried out till moisture is Not More Than 5%.
6. Packed under-pressure in airtight container.

Microscopy Of
Digitalis
purpurea
o Dorsiventral leaf
o Plenty of simple covering & glandular trichome
on both surfaces
o Covering trichome: uniseriate, 3-4 celled long,
collapsed cells, acute apex & finely warty cuticle.
o Glandular trichome: short unicellular stalk,
bicellular or rarely unicellular head
o Anomocytic (irregular celled) stomata
o Trichome-stomata more in lower surface
o Pericycle: parenchymatous above &
collenchymatous below
o Calcium oxalate crystals are absent

Chemical
constituents of
Digitalis purpurea
● It contains 0.2-0.45% mixture of both
primary and secondary cardiac
glycosides.
● Purpurea glycosides A and B and
Glucogitoloxin are primary glycosides. • Primary glycosides are less absorbed and
less stable than secondary glycosides such
as digitoxin, gitoxin, gitaloxin.
• Digitalis contains about 30 Glycosides
which include verodoxin, glucoverodexin
and odoroside H.
• Additionally, it also contains 2 saponin
glycosides – digitonin and gitonin.
Digitoxigenin

Chemical Tests for
Digitalis
Boil 1g of finely
powdered digitalis
with 10ml 70% alcohol
(2-3 mins) and filter
Filtrate + 5ml water
+ 0.5ml strong
solution of lead
acetate. Shake well
and sperate the
filtrate
Transfer to a
test tube
containing
2ml conc.
H₂SO₄
Extractive is dissolved
in glacial acetic acid,
cooled + 2 drops of
FeCl3 solution
Reddish brown layer
acquiring bluish-green
colour after standing is
observed due to presence
of digitoxose
Clear filtrate + equal
vol. of CHCl₃.
Evaporate to yield
extractive
Keller-Kiliani Test for Digitoxose :

Chemical Tests for
Digitalis
Dissolve the Extract
in pyridine
Sodium nitroprusside
solution and make it
alkaline
+
+
Baljet Test :
Pink or Red
colour is
produced
Legal Test :
Section of Digitalis Sodium picrate
solution
Yellow to Orange
colour is produced

STANDARDS OF QUALITY
● Foreign organic matter : Not more than 2%
● Loss on drying : Not more than 5% w/w, by drying to constant
weight at 105°C
● Acid – insoluble ash : Not more than 5%

Uses of
Digitalis
purpurea
ADULTERANTS
Digitalis leaves are adulterated with :
• The leaves of Verbascum Thapsus
• The leaves of Primula vulgaris
• The leaves of Symphatum officinale
● It is used in the treatment of congestive
cardiac failure.
● It is used in the treatment of atrial fibrillation,
atrial flutter, superventricular tachycardia.
● It has a good effect on kidney and results in
good diuresis.
● Also used in case of epilepsy and acute
mania.
● The major disadvantage of digitalis is that it
has ‘cumulative effect’ so administration of
drug should be under strict medical
supervision.
STORAG
E
Digitalis is stored in a well closed container in a
cool place away from light. Leaves must not
contain more than 5% of moisture because it
results in loss of cardiac activity. The powder is
stored in containers with dehydrating agents like
silica gel to absorb excess moisture.

Synonym : Woolly foxglove, Grecian foxglove
Biological source : Dried leaves of Digitalis
lanata.
Family : Scrophulariaceae
● Shape : Sessile, linear lanceolate
● Size : 30cm long, 4cm wide
● Margin : Entire
● Apex : Acuminate
● Trichomes : 10-14 celled non-
glandular trichomes
DIGITALIS
LANATA MORPHOLOGY

GEOGRAPHICAL SOURCES DIGITALIS
LANATA
USA
INDIA
NETHERLANDS
ECUADOR

1. Biennial herb (a plant which blooms in its second year and then dies)
2. Perennial herb (perennial (Latin per, "through", annus, "year") is a plant that lives
for more than two years)
3. Light (sandy), medium loamy and heavy clay soil
4. Prefers acid-alkaline-neutral soil
5. Can grow in semi-shade or no shade.
6. Dry or moist soil
7. Propagated by seeds
8. Seeds are sown in early spring in a cold frame
9. Germination in 2-4 weeks at 20° C
LANATA

COLLECTION OF DIGITALIS
LANATA
When they are large enough to handle, seedlings are
transplanted into individual pots and planted them out in the
summer.

Microscopy Of
Digitalis lanata
o Upper Epidermis : Single layered,
covered with a thick cuticle, cells have
wavy and thick walls; Stomata are also
occasionally seen on the upper
epidermis.
o Trichomes : two kinds of trichomes are
seen in the upper epidermis, multicellular,
uniseriate covering trichomes and
glandular trichomes with unicellular stalk.
o Lower epidermis : Identical to upper
epidermis but numerous stomata.
o Mesophyll : It is differentiated into
palisade and spongy parenchyma.
o Vascular bundle is present towards the
ventral surface (upper epidermis) of the
midrib.
o Calcium oxalate crystals are absent

Chemical
constituents of
Digitalis lanata
● It contains 5 primary glycosides and in
all about 70 glycosides.
• The primary glycosides are identified as
Lantasoide A, B, C, D, and E.
• The aglycones – digoxigenin and
diginatigenin are specific to Digitalis lanata.

Uses of
Digitalis lanata
Allied Species
• Digitalis lutea : (Straw Foxglove)
This drug is as potent as Digitalis
purpurea.
It is supposed to have less irritation and
is
used as a common substitute for the
official
drug.
• Digitalis thapsi : (Spanish Foxglove)
This drug is 1.25 to 3 times more potent
than Digitalis purpurea.
● It shows 3-4 times more activity than
Digitalis purpurea.
● It is the commercial source of digoxin,
lanatoside C.
● It is used in the treatment of congestive heart
failure and atrial fibrillation.
● Use should always be supervised by a
qualified practitioner since in excess they
cause nausea, vomiting, slow pulse, visual
disturbance, anorexia and fainting.

Comparison between Digitalis purpurea and Digitalis lanata
Digitalis Purpurea Digitalis lanata
It has a tea-like odour and is
bitter in taste
It has tea-like odour
Contains Purpurea Glycoside A and
B along with Saponins, flavonoids
and Anthraquinones.
Contains Lanatoside A, B, C, D, E
Sclerenchyma and calcium oxalate
crystals are absent
Calcium oxalate crystals are
absent
Petiole is winged Petiole is sessile
Surface of leaf is pubescent
(covered with fine soft hair)
Surface of leaf shows cilia at
lower third part.
Numerous fragments of non-
glandular hair
Glandular hair are present

Synonym : White squill, scilla, Drimia
maritima
Biological source : Dried slices of bulbs of
Urginea
maritima
Family : Liliaceace
● Colour : Translucent yellowish-white
● Odour : Slight and characteristic
● Taste : Bitter and acrid
● Size : Entire bulb is 12-15 cm in
diameter and 18-20 cm in height.
The slices are 3-6 cm in length
and 4-8 mm in width.
● Shape : The slices are concavo-
convex shaped
EUROPEAN
SQUILL
MORPHOLOGY

GEOGRAPHICAL SOURCES EUROPEAN
SQUILL
MOROCCO
GREECE
SPAIN
ITALY
ALGERIA
FRANCE

The plant prefers light (sandy) and medium (loamy) soils and requires
well-drained soil.
The plant prefers acid, neutral and basic (alkaline) soils.
The plant can tolerate strong winds but not maritime exposure.
Seeds are sown as soon as it is ripe in a greenhouse.
The seeds are sown thinly so that the seedlings can be left in the pot
for their first growing season.
Once the plant becomes dormant the young bulbs are divided, placing
two to three bulbs in each pot.
CULTIVATION OF EUROPEAN
SQUILL

COLLECTION OF EUROPEAN
SQUILL
Bulbs are dug out from the soil in the end of August and external
scaly leaves and central portion are removed.
The slices are dried completely in the sunlight or by heat of the stove.
The drug is stored in airtight and especially in moisture proof
containers.

Microscopy Of
Squill
o Single layer of polygonal
elongated epidermis is present
which is covered with the
cuticle.
o Mesophyll region consists of
acicular calcium oxalate
crystals, mucilage sheath, small
round starch grains and
vascular bundle.
T.S of Squill

Chemical
constituents of
European Squill
● Squill contains cardiac glycosides
of bufadienolide type.
● Scillaren-A is the most important
(about 2/3𝑟𝑑
of total glycosides)
● It also contains Scillaren-B
• It contains Glucoscillaren-A and
Proscillaridin-A in small amounts.
• Along with that it contains xanthoscillide,
flavonoids, mucilage, calcium oxalate,
sinistrin and a volatile substance which
causes irritation

Red variety of squill contains :
1. Anthocyanin (red color)
2. Scilliroside (glycoside which is toxic to rat)

Comparison between Scillaren A and Scillaren B
Nature Crystalline Amorphous
Colour Colourless White/ Yellowish
white
Taste Bitter Very Bitter
Odour Odourless Odourless
Solubility Comparatively less
water soluble
More soluble in
water, ethanol and
methanol
Activity Less active More active
Stability Less stable More Stable
SCILLAREN - A SCILLAREN - B
PROPERTIES

Chemical Tests for European
Squill
Drug
extracted
with CHCl3
Few drops of acetic
anhydride
+ +
Appearance of Violet ring which turns
Blue due to presence of sterol
Liebermann Test For Sterols :
Concentrated Sulphuric
acid (from side wall of
test tube)

Chemical tests for European
Squill
Mucilage + Corallin
soda
Yellow
stains
Red
stains
Mucilage + Iodine
Mesophyll region of squill contains mucilage, calcium oxalate and xanthoscillide

Uses of
European
Squill
ADULTERANTS
The common adulterants of squill plant
are the bulbs of different species of
ledebouria.
● It is a potent cardiotonic without having any
cumulative effect (unlike Digitalis).
● It is mostly employed in small doses as an
effective expectorant specially in chronic
bronchitis.
● It causes vomiting in relatively higher doses
● It also has some diuretic properties
● squill glycosides possess high therapeutic
index and rapid elimination.

Synonym : Jangli pyaz, sea onion, scilla,
urginea
Biological source : Dried slices of bulbs of
Urginea
indica kunth
Family : Liliaceace
● Colour : Squill bulbs are yellowish to white
● Odour : Slight and characteristic
● Taste : Bitter and acrid
● Size : 30-60 mm in length and 3-8 mm
broad.
● Shape : The slices are united in groups of
4-8 which are curved
INDIAN
SQUILL MORPHOLOGY

GEOGRAPHICAL SOURCE OF INDIAN SQILL
KONKAN COAST
SAURASHTRA
LOWER HIMALAYAS

Though it is not been cultivated, it grows well at a temperature
of 15–20°C and in sandy soil.
The bulbs grow to full size within 5 years.
The bulbs are collected after flowering, cut in to small slices
and dried under sun.
CULTIVATION AND COLLECTION
OF INDIAN SQUILL

Chemical
constituents of
Indian Squill
● Indian squill contains about 0.3% of
cardiac glycosides.
● Scillaren-A and Scillaren-B are the
major constituents.
● The drug also contains
glucoscillaren A and enzyme
Scillarenase.
• The other contents of drug are
mucilage (about 40 %) and calcium
oxalate

Chemical tests for Indian
Squill
Mucilage + Corallin
soda
Reddish-purple
stains
Red
stains
Mesophyll + Iodine
Water

Uses of Indian
Squill
ADULTERANTS
Commercial samples of Indian squill in
the market, are mixed with Scilla
hyacintoiana.
● It is a potent cardiotonic without having any
cumulative effect (unlike Digitalis).
● It is mostly employed in small doses as an
effective expectorant specially in chronic
bronchitis and asthma.
● It shows some anti-cancer activity against
human epidermoid carcinoma.
● It also has some diuretic properties

MARKETED PREPARATIONS
OF CARDIAC GLYCOSIDES

• Generic name : Digoxin.
• Brand name : Lanoxin, Lanoxicaps,
Cardoxin, Digitek.
• It is a cardiotonic glycoside obtained mainly
from Digitalis lanata.
• Digoxin has positive inotropic and negative
chronotropic activity.
• It is used to control ventricular rate in atrial
fibrillation and in the management of
congestive heart failure with atrial fibrillation.
Marketed
Preparations of
Cardiac Glycosides
Lanoxin Pediatric injection
Cardoxin 0.25 mg
tablets
DIGOXIN

• Indications : Heart failure, atrial fibrillation
• Dosage : In Adults- oral solution 0.05mg/mL
, Injectable solution- 0.1mg/ml.
• Contraindications : Digitalis toxicity,
ventricular tachycardia/fibrillation, obstructive
cardiomyopathy.
• Side effect : Extra beats, anorexia, nausea
and vomiting. Diarrhoea in elderly, confusion,
dizziness, drowsiness, restlessness,
nervousness, agitation and amnesia,
Marketed
Preparations of
Cardiac Glycosides
Lanoxin 250 micrograms tablets

• Indications : Congestive heart failure , atrial
flutter, atrial tachycardia, atrial fibrillation.
• Dosage : Adult and child age 12 years and
above, orally 1.2 to1.6 mg per day in divided
dose. Child 1 to 2 year age 0.04 mg per kg
weight.
• Contraindications : Hypersensitivity,
hypokalemia, pregnancy, lactation, hepatic
disease, A.V. block, ventricular tachycardia.
• Side effect : Hypersensitivity, hypokalaemia,
pregnancy, lactation, hepatic disease, A.V.
block, ventricular tachycardia.
Marketed
Preparations of
Cardiac Glycosides
Digoxin- Sandoz 0.25mg tablets
DIGITOXIN
DIGITOXIN is similar in structure and effects to
digoxin. It is excreted via liver. It could be used in
patients with poor or erratic kidney function. It is
now rarely used.

• Action : Digoxin immune FAB do not
allow digoxin to bind to the sites of action
and reverse digoxin toxicity.
• Indications : Digoxin or digitoxin toxicity.
• Contraindications : Hypersensitivity,
mild digoxin toxicity, children ,
pregnancy, lactation.
• Side effects : Facial swelling, redness,
rapid respiration rate, low cardiac output.
Marketed
Preparations of
Cardiac Glycosides
DigiFa
b
DIGIBIN
D
Digoxin Immune
Fab

Dixin Tablets IP 0.25
mg
Marketed
Preparations of
Cardiac Glycosides
Digoxin Tablets, USP 0.125 mg

Digoxin Elixir .05mg/ml
60mL
Marketed
Preparations of
Cardiac Glycosides
Lanoxin Paediatric 50 mcg /ml Elixir
Syrup

THANKS!
● References:
1. Pharmacognosy by C.K.
Kokate, A.P. Purohit, S.B.
Gokhale
2. Pharmacy180.com
3.https://www.slideshare.net/
priyankagoswami/glycosidesem
-8
4. Essentials of medical
pharmacology by K.D Tripathi

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