Cardiac glycosides are naturally occurring drugs that have beneficial effects on heart contractility but can also be toxic. Digoxin is the only cardiac glycoside currently used clinically. They work by inhibiting the sodium-potassium ATPase pump, increasing intracellular calcium and contractility. While they increase contractility and are used to treat congestive heart failure, cardiac glycosides can also cause arrhythmias and other adverse effects. Their use requires monitoring due to the risk of toxicity.

1. PREPARED BY-
Suresh Kumar Ghritlahare
Assist. Professor
SRU, Raipur, (C.G.)

2. Cardiac Glycosides
 These are glycosidic drugs having cardiac inotropic
properties and occuring in naturally having both beneficial
and toxic effect on the heart and have played oustanding
role in the therapy of congestive heart failure (C.H.F.).
 Cardiac glycosides are found in several plants and in toad
skin (Bufotoxin). Digitalis lanata is the source of Digoxin,
the only glycoside that is currently in use. Others like
Digitoxin (from Digitalis purpurea) and Ouabain (from
Strophan thus gratus), etc. are no longer clinically used or
marketed.
 By convention the term, ‘Digitalis’ has come to mean ‘a
cardiac glycoside’.

3. Chemistry
 The cardiac glycosides consist of an aglycone (genin) to
which are attached one or more sugar (glucose or
digitoxose) moieties.
DIGOXIN
 Theaglycone consists of
cyclopentanoperhydrophenanthrene (steroid) ring to which
is attached a 5 or 6 membered unsaturated lactone ring.

4. Source of Cardiac Glycosides
S. No. Source Glycosides
1. Digitalis Purpurea (Leaf) Digitoxin, Gitoxin, Gitalin
2. Digitalis lanta (Leaf) Digitoxin, Gitoxin, Digoxin
3. Strophanthus gratus (Seed) Strophanthin-G
4. Thevetia (Nut) Thevetin
5. Convalleria Majalis Convallotoxin
6. Bufo Vulgaris (Toad Skin) Bufotoxin

5. Mechanism of Action
 Cardiac glycosides basically target myocardium of
heart.
 Cardiac glycosides selectively inhibit Na+/K+
ATpase and decrease availability of Na+ ion at
extracellular sites.
 In response to decrease availability of sodium at
extracellular site sodium exchanger get inhibited
 Increase Ca++ ion concentration intracellularly also
increase sarcolema Ca++ load.
 Increase force of cardiac contraction is positive
inotropic effect.

7. Pharmacological Actions
1. Heart : Digitalis has direct effects on myocardial
contractility and electrophysiological properties.
I. Force of contraction: Digitalis causes a dose dependent
increase in force of contraction of heart—a positive inotropic
action.
II. Rate Heart: rate is decreased by digitalis.Bradycardia is
more marked in CHF patients.
III. Electrophysiological properties:
(a) Action potential (AP ): The resting membrane potential
(RMP) is progressively decreased (to less negative values)
with increasing doses.
(b) Conduction: A-V conduction is demonstrably slowed by
therapeutic doses.
(c) ECG : Therapeutic doses of digitalis produce changes in the
ECG.

8. Fig: Effect of digitalis on Purkinje fibre action potential

9. 2. Blood vessels: Digitalis has mild direct vasoconstrictor
action—peripheral resistance is increased in normal
individuals.
 3. Kidney: The retained salt and water is gradually
excreted. No diuresis occurs in normal individuals or in
patients with edema due to other causes.
4. CNS: Digitalis has little apparent CNS effect in
therapeutic dose. Higher doses cause CTZ activation →
nausea and vomiting.

10. Pharmacokinetics
Absorption: Bioavailability of digoxin tablets from
different manufacturers may differ. Presence of food
in stomach delays absorption of digoxin.
Distribution: The volume of distribution of digoxin is
large (6–8 L/Kg). It is concentrated in the heart (~20
times than plasma), skeletal muscle, liver and kidney.
Metabolism: Metabolized by liver
Excretion: Digoxin is primarily excreted unchanged by
the kidney:

11. Adverse Effects
Extracardiac: Anorexia, nausea, vomiting and
abdominal pain are usually reported first: are due to
gastric irritation, mesenteric,CTZ stimulation. Fatigue,
malaise, headache, mental confusion, restlessnessetc.
Cardiac: Almost every type of arrhythmia can be
produced by digitalis: pulsus bigeminus, nodal and
ventricular extrasystoles, ventricular tachycardia and
terminally ventricular fibrillation.

12. Contraindications
 Hypokalemia
 Elderly, renal or severe hepatic disease
 Myocardial ischaemia
 Myxoedema:
 Ventricular tachycardia
 Acute myocarditis

13. Uses
1. Congestive heart failure:
 Systolic dysfunction: The ventricles are dilated and
unable to develop sufficient wall tension to eject
adequate quantity of blood.
 Diastolic dysfunction :The ventricular wall is thickened
and unable to relax properly during diastole; ventricular
filling is impaired because of which output is low.
2. Cardiac arrhythmias
 Atrial fibrillation (AF)
 Atrial flutter (AFI)
 Paroxysmal supraventricular tachycardia (PSVT)

14. REFERENCES
 Tripathi KD, “Essentials of Medical Pharmacology”
published by Jaypee Brothers Medical Publishers (P) Ltd,
Seventh Edition: 2013, New Delhi, p.p. no-512-519.