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CardiacCardiacGlycosidesGlycosides

Santos, Rafael Lorenz S.Santos, Rafael Lorenz S.Tan, Noel Jr. C.Tan, Noel Jr. C.

Tan, RoxanneTan, Roxanne GilleaGillea G.G.TomenbangTomenbang,, AndreyAndrey Paul C.Paul C.

Yee, Angelica Mae G.Yee, Angelica Mae G.

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Definition Cardiac glycosides are aka:

Digitalis glycosides, Cardioactiveglycosides, Cardiotonic glycosides,

Cardiac steroids

Both beneficial and toxic to the heart

Steroid compounds that can increase

cardiac output (CO) and alter electricalfunctions of the heart

Have a narrow margin of safety

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History

Plants that contain cardiac steroids havebeen used aspoisons and heart drugssince 1500 B.C.

Extracts have been used as:

Arrow poisons, Emetics, Diuretics,Heart tonics

Used widely in treating congestive heartfailure (CHF)

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History

3,000 years ago,Ancient Egyptians have

known of plants with cardiac glycosides

Until 18th century,William Witheringpublished a monograph describing the

clinical effects of the foxglove plant.

An Account of the Foxglove and Some

of Its Medical Uses: With Practical

Remarks on Dropsy and OtherDiseases

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Chemical Structure

Cardiac glycosides are triterpene molecules

Combination of a genin (aglycone) and a

sugar moiety (glycone) linked across anoxygen atom

Fig.1 Chemical structure of digoxin, a cardioactive glycoside

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Genin (Aglycone)

Basic structure of asteroid nucleus to

which a 5- or 6-membered unsaturated

lactone ring is attached at C-17

The 5-membered unsaturated lactone

ring is named cardenolides

The 6-membered unsaturated lactone

ring is named bufadienolides

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Cardenolide and

Bufadienolide The steroid nucleus and the lactone ringare essential forpharmacologic activity

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Sugar Moiety (Glycone)

Attached via the aglycone or the C-3

hydroxyl group

The majority of the saccharides incardiac glycosides are highly specific

The sugar molecule in C-3 affects the

pharmacokinetic variables

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Digitoxin

An example of cardiac glycoside is

digitoxinfrom Digitalis. Attached to

digitoxigenin is digitoxosevia the C-3

hydroxyl group

Fig.4 Digitoxin, differs only by the OH group in digoxin at C-12

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Types

Depending on the nature of lactone ring at C-

17, Cardiac glycosides are classified into two

groups, cardenolides and bufadienolides

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Cardenolides C23 steroids with an

unsaturated 5-membered lactone ring

Naturally occurringsubstance

Efficacious intreatment ofheartdiseases

Found in almost allparts of the plant

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Cardenolides

Abundant in theApocynaceaeandAsclepiadaceae

Digitoxigenin,Gitoxigenin,Gitaloxigenin,

Digoxigenin,Diginatigenin,Strophathidin,Ouabagenin

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Bufadienolides C24 steroids having a

doublyunsaturated 6-membered lactonering

Less widelydistributed in nature

Therapeutically oflittle use ascardioactive drugs

because of lowtherapeutic index (TI)and its side effects

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Bufadienolides

Found in some

Liliaceaeand

Ranunculaceae

ScillaridinA,Scill

iphaesidin,Helleb

rigenin

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Extraction Procedure

Reflux Method

Process ofboiling reactants while

continually cooling the vaporreturning itback to the flask as a liquid

Thus, heating under reflux willprevent theloss of any solvents and the compound

Liquid being heated will travel only partlyup the condenser tube before condensing

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+

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R

E

FL

U

X

ME

TH

O

D

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Reflux Method

Below the condensation point, solventwill be seen running backinto the flask

Aboveit, the condenser will appear dry

The boundary between the two zoneswill be clearly demarcated, and a reflux

ring or a ring of liquid will appear there AllCardiac glycosides can be extractedby this method (Wagner 1996)

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Schematic Diagram of

Reflux Method

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Medicinal Uses

Of the types of cardiac glycosides,cardenolides have been proven to be themost medicinally important

Digitalis lanata lanatosidesand digoxinare both used as cardiac drugs

Stophantusspecies oubain is used in

biological assays as standard and inpreparation ofouabaininj. as a cardiacdrug

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Medicinal Uses

Bufadienolides are less found in nature

than cardenolides

Hence, they are seldom used inmedicinal practices

It is used as an expectorant at minimal

doses for it may cause vomiting andmay promote gastric irritations