Congestive heart failure

1. “Drugs Used in Congestive Heart
Failure”
By
Harun M. Patel (M. Pharm., Ph.D., Post Doc.)
R. C. Patel Institute of Pharmaceutical Education & Research
Shirpur
Mobile Number: 08806621544; Email: patelsynthetic@gmail.com

2. What is Congestive Heart Failure ?
“Congestive heart failure is a condition
that affect the Pumping power of heart
muscle and that may lead to the Heart
Failure”
CHF develops when your ventricles can’t
pump enough blood volume to the
body. Eventually, blood and other fluids
can back up inside Lungs, abdomen,
liver and limbs

3. Types of Congestive Heart Failure
A) Left Sided CHF:
 Systolic heart failure occurs when
the left ventricle fails to contract
normally. This reduces the level of
force available to push blood into
circulation. Without this force, the
heart can’t pump properly.
 Diastolic failure, or diastolic
dysfunction, happens when the
muscle in the left ventricle becomes
stiff. Because it can no longer relax,
the heart can’t quite fill with blood
between beats.
A) Right Sided CHF:
 It occurs when the right ventricles has
difficulty in pumping the blood to lungs.
In such condition blood reversed or
remain in blood vessel, which causes
fluid retention in lower extremities,
abdomen and other vital organ.

4. Reasons for Congestive Heart Failure
 Coronary artery disease: Coronary artery disease (CAD), a disease of
the arteries that supply blood and oxygen to the heart, causes decreased blood
flow to the heart muscle. If the arteries become blocked or severely narrowed,
the heart becomes starved for oxygen and nutrients.
 Heart attack: A heart attack occurs when a coronary artery becomes suddenly
blocked, stopping the flow of blood to the heart muscle. A heart
attack damages the heart muscle, resulting in a scarred area that does not
function properly.
 Cardiomyopathy: Damage to the heart muscle from causes other than artery
or blood flow problems, such as from infections or alcohol or drug abuse.
 Conditions that overwork the heart: Conditions including high blood
pressure, valve disease, thyroid disease, kidney disease, diabetes, or heart
defects present at birth can all cause heart failure. In addition, heart failure can
occur when several diseases or conditions are present at once.

5. Drugs used in CHF
Cardiac Glycoside : Digoxin and Digitoxin
B1 Agonist: Dobutamine
Inhibitors of cardiac Cyclic-AMP phosphodiesterase: Amrinone, Milrinone
Peptides: Nesiritide
Endothelin Antagonist: Bosentan, Tezosentan

6. Cardiac Glycoside
Cardiac glycoside consist of Aglycone
portion and Glycone portion.
The aglycone consists of
cyclopentanoperhydrophenanthrene
(steroid) ring to which
is attached a 5 or 6 membered
unsaturated lactone ring.

7. Cardiac Glycoside
Classification
Based on substitution at C-17, Cardiac
glycosides are further classified as
Bufadienolides and Cardenolides.
Bufadienolides: Six membered lactone
ring with
Cardenolides: Contains cyclic
butyrolactone ring

9. Digitoxin and Digoxin are obtained from the Digitalis Lanata.
Both the contains Digoxigenin as a aglycone portion and three sugars

12. Nesiritide Peptides
Nesiritide is a 32 amino acid sequence
peptide manufactured from E.coli
using r-DNA technology.
Nesiritide

13. MOA of Nesiritide
Nesiritide is the endogenous peptide that exerts a direct vasodilatory
effect on arterial and venous blood vessel along with diuretic activity.
Binding of Nesiritide to the Guanylate Cyclase receptor leading to
increase in intracellular cGMP, which causes the inhibition of of
phosphorylation of the Myosine. Hence Actin will not bind with
Myosine. It also inhibit the entry of calcium

15. Endothelin Antagonist
Bosentan Tezosentan

16. Mode of Action
The endothelium is a thin membrane that
lines the inside of the heart and blood
vessels. Endothelial cells release substances
that control vascular relaxation and
contraction.
Endothelin-1 is a neurohormone which
binds to endothelin A (ETA and ETB)
and B receptor in the endothelium and
vascular smooth muscle. Binding of
Endothelin-1 to (ETA and ETB)
produces the vasoconstriction.
Bosenntan and Tezosentan are dual
inhibitor of ETA and ETB and causes the
vasodilation