Drugs used in congestive heart failure

A condition in which the heart is unable to pump sufficient blood to meet the metabolic demand
of the body and also unable to receive it back because every time after a systole.

Cardiac glycosides
• The cardio active steroids and their glycosides are widely distributed in nature and have
characteristic actions on contractility and electrophysiology of heart.
• Their discovery is an example of folk lore medicine, known to ancient people like Romans
and Egyptians.
• Most glycosides are obtained from leaves of the foxglove, Digitalis purpurea or Digitalis
lanata.
• William Withering (1785) was the first to notice their effects on heart; cardiac glycosides
are the combination of an aglycone or genin, and one to four sugars.
• The steroidal aglycone of the glycosides is responsible for cardiac activity and sugars
provide favorable solubility and distribution, and thus, affect its potency and duration of
action.
• Now these glycosides are used less frequently.
The two types of cardiac glycosides used to treat CHF are digoxin and digitoxin, the primary being
digoxin.
Chemistry of Cardiac glycosides
The term genin at the end refers to only the aglycone portion (without the sugar). Thus the word
digitoxin refers to a agent consisiting of digitoxigenin (aglycone) and sugar moieties (three).
Aglycone moiety
 Rings A/B and C/D are cis fused while rings B/C are trans fused. Such ring fusion give the
aglycone nucleus of cardiac glycosides the characteristic ‘U’ shape.

 The steroid nucleus has hydroxyls at 3 and 14 positions of which the sugar attachment uses
the 3-OH group. 4-OH is normally unsubstituted.
 Additional hydroxyl groups at 12 and 16 positions greatly affect the duration of action.
 The lactone moiety at C-7 position is an important structural feature.
Plant sources provide a 5-membered unsaturated lactone.
Animal sources provide a 6-membered unsaturated lactone.
Sugar moiety
 One to 4 sugars are found to be present in most cardiac glycosides attached to the 3β-OH
group.
 The sugars most commonly used include L-rhamnose, D-glucose, D-digitoxose, D-
digitalose, D-digginose, D-sarmentose, L-vallarose and D-fructose.

MOA:
Digoxin is a positive inotropic agent.
• Digoxin also reduces sympathetic responses via the vagus nerve, which will reduce overall
heart rate.
• The combination of increased contractility and reduced heart rate creates a more efficient pump
for cardiac output
Endothelin-1 antagonists
Bosentan/Tezosentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and
endothelin-B (ET-B) receptors.