cardiac glycosides lecture notes-2012-2013

CARDIAC GLYCOSIDES

• The genins or aglycones of all cardiac

glycosides are steroidal in nature

• May be referred to as steroid glycosides

• They act as cardiotonic agents

• Enhance the tone of the heart

• Excitability

• Contractibility of the cardiac muscle

• Also the improved circulation tends to

improve renal secretion

• This relieves oedema often associated

with heart failure

Structural Characteristics of Cardiac Glycosides

• This is always involved in a glycosidic

linkage to a mono, di, tri, or tetra

saccharide

• Most sugars that are found in cardiac

glycosides are uncommon deoxy-sugars

• E.g Digitoxose, Cymarose, Thevetose

C

CHO

C

C

C

CH3

OH

OH

OH

H2 C

CHO

C

C

CH3

OH

OH

H2

CHO

C

C

CH OH

HC OCH3

OH

HCH3O

C OHH

CH3

Digitoxose Cyamarose Thevetose

O

R

OH

CH3

Sugar

Lactone ring

1

2

3

45

10

67

8

9

1112

13

1415

16

17

Types of cardiac glycosides

• The steroid aglycones or genins are of 2

types

• Cardenolides

• Bufadienolides

THE CARDENOLIDES• They are more prevalent in nature

• Cardenolides are C23 steroids

• These have α,β-unsaturated 5-membered

lactose ring in position C-17

2 main types:• Digitalis glycosides • Strophanthus glycosides

O

R

OH

CH3OH

Sugar

1

2

3

45

10

67

8

9

1112

13

1415

16

17

O OCardenolides

Digitalis glycosides R=CH3Strophanthus glycosides R=CHO OR CH2OH

The Digitalis group

These include:

• D. purpurea, D. dubia, D. ferruginea

• D. lanata, D. grandiflora, D. nervosa

• D. lutea D. mertonensis, D. subalpina

• D. thapsi

Chemical constituents

• digitoxin

• gitoxin

• digoxin

Digoxin

• Digoxin is the most widely used of

cardiotonic glycosides

• Obtained from the leaves of D. lanata

THE BUFADIENOLIDES

• This group of cardioactive agents includes

the following:

• Squill glycosides (scillarins)

• Toad poison (Bufotoxin)

Botanical source

• Obtained from the bulbs of varieties of

squill

• Family = Liliaceae

• Derives name from the generic name for

the toad (Bufo)

• Possesses doubly unsaturated 6-

membered lactone ring in position C-17

• Bufadienolides are C24 steroid

O

OH

R1R2

Sugar

1

2

3

45

10

67

8

9

1112

13

1415

16

17

O

O

Bufadienolides

Squill glycosides R1=OH, R2=H Bufotoxin R1 & R2 = ester group

Bufadienolides from Squill• These glycosides include the following:

• Scillarin A

• Scillarin B

Uses

• A potent cardiotonic

• As expectorant specially in chronic

bronchitis

• As stimulant

• It is used as a very effective expectotant

both in asthma and chronic bronchitis

• It may possess anticancer

• Produces diuresis

• It causes emesis in relatively higher doses

• Chemical colour reactions have been

evolved to be used as the qualitative tests

either for:

• the various glycosides

• or their corresponding aglycones

TEST FOR CARDIAC GLYCOSIDES

1 Kellar-Kiliani Test

The glycoside is dissolved in glacial acetic acid containing a trace of FeCl3, add conc. H2SO4 along the side of the test tube to settle at the bottom (for deoxy sugars e.g. digitoxose)

A reddish brown colour changing to bluish green colour appears at the junction of two reagents within 2-5 minutes spreading slowly into the acetic acid layer

2. Kedde’s Test A solution of glycosides is treated with a small amount of Kedde’s reagent (Cardenolides)

Development of a blue or violet colour that fades out in 1- 2 hours shows its presence

MEDICINAL IMPORTANCE OF CARDIAC GLYCOSIDES

• Cardiotonics

• Congestive heart failure

• Rheumatic heart disease

• Atherosclerosis

• Diuretics

Official Cardiac Drugs

• Digitalis leaf (digitalis tablets)

• Digitoxin tablets

• Digoxin injection