Cardiac glycosides are a group of drugs derived from plants that act on the heart by increasing the force of contraction. They are used to treat atrial fibrillation and congestive heart failure by slowing the heart rate. Digoxin and digitoxin are the main cardiac glycosides available, obtained from Digitalis plants. They work by inhibiting the sodium-potassium pump in heart cells, increasing intracellular sodium and calcium levels to boost contraction force.

1. CARDIAC GLYCOSIDES
• Cardiac glycosides or digitalis essentially refer to a
group of chemically and pharmacologically related
drugs, that act on the heart by causing
atrioventricular conduction and vagal tone.
• They are invariably employed to slow the heart rate in
atrial fibrillation and also administered in congestive
heart failure.
• A large number of ‘drug substances’ are able to
enhance the force of contraction of the heart. It is,
however, pertinent to state here that this ionotropic
activity may be specifically of great utility and
importance in the ultimate treatment of congestive
heart failure

2. Cardiac Glycosides
• Drugs originally obtained from plant source, Digitalis
purpurea and Digitalis lanata
• Digoxin and digitoxin are the only cardiac glycosides
currently available
• Main pharmacologic effect of cardiac glycosides is to
increase the contractile force of myocardial
contraction
• Cardiac glycosides also decrease heart rate and
atrioventricular conduction

3. Digoxin
The side chain of
digoxin is made up of
three molecules of
digitoxose in a
glycosidic linkage,
which upon
hydrolysis yields the
aglycone, digoxigenin
(C23 H34 O5).
Digoxigenin is
obtained from the
leaves of Digitalis
lanata Ehrh. (Family :
Scrophulariaceae). Its
cardiotonic actions
are very much alike
to those of digitalis. It
is used in the
treatment of
congestive heart

4. Digitoxin
Digitoxin is obtained from
Digitalis purpurea Linne,
Digitalis lanata Ehrh, and
other suitable species of
Digitalis.
Its side chain is comprised of
three molecules of digitoxose
in a glycosidic linkage.
Hydrolysis affects removal of
the side chain to yield the
aglycone, digitoxigenin
(C23H34O4).
Digitoxin is the most potent
of the digitalis glycosides
besides possessing its
inherent maximum
cumulative action

5. Mechanism of Action
• Cardiac glycosides inhibit Na/K adenosine
triphosphatase, the “sodium pump” which causes
more Na to remain inside myocardial cells
• Increased intracellular Na stimulates Na/Ca exchange
that brings more Ca inside heart cells to increase the
force of contraction
• Cardiac glycosides also stimulate the vagus nerve
which decreases heart rate

6. Pharmacokinetics and Dosing
• Digoxin is water soluble and eliminated mostly
unmetabolized by the urinary tract
• Digitoxin is more lipid soluble, requires metabolism,
and has a longer half-life
• In acute CHF, initial “digitalization” doses are
administered to rapidly attain effective therapeutic
concentration
• Lower daily maintenance doses are then given to
maintain desired therapeutic concentrations

7. Electrolyte and Cardiac Glycoside
Interactions
• Low serum potassium (K) levels “hypokalemia”
increase drug toxicity and can cause cardiac
arrhythmias
• High serum potassium levels “hyperkalemia”
decrease the actions of the cardiac glycosides
• Increased serum calcium levels “hypercalcemia”
can increase the actions and toxicity of the
cardiac glycosides

8. Adverse Effects
• Common complaints include headache,
dizziness, nausea, and vomiting
• Visual disturbances “halo effect” around lights
often signals overdosage
• Bradycardia, ectopic beats, and a variety of
other cardiac arrhythmias can occur and can
be life-threatening

9. Diuretic Therapy of CHF
• Diuretic drugs are used to eliminate excess
sodium and fluid retention
• Elimination of excess fluid allows the heart to
function more efficiently
• Diuretics can be administered with cardiac
glycosides and other drugs used to treat CHF

10. Vasodilator Therapy of CHF
• Vasodilator drugs relax and dilate blood
vessels
• Vasodilation decreases peripheral resistance,
allows more efficient blood flow, and usually
increases cardiac output
• Angiotensin-converting enzyme inhibitors and
angiotensin receptor blocking drugs are
particularly useful in CHF