Heparin: Source, Structure, Chemistry, MOA and Uses

Molecular and Cellular aspects of Heparin along with Source, Structure, Chemistry, MOA and Uses.

1. HEPARIN
Presented by: Megh.P.Vithalkar
M.PharmSemester-1 (2020)
Department of Pharmacology.
Goa college of Pharmacy, Panaji-Goa.

2. INTRODUCTION
•Heparin is a naturally occurring anticoagulantthat prevents
the formation of blood clots.
•Heparin does not itself break down existing clots, but
enhancesthe body’s natural mechanisms involved in
dissolving clots.
•Heparin is one of the oldest medicines currently in use.
•It was first discovered in 1916 before the United States Food
and Drug Administration had been established and it did
not enter clinical trials until 1935.
•Heparin was first discovered by Jay McLean and William
Henry Howell in 1916.

3. NATURAL SOURCE OF HEPARIN
•Heparin, a natural anticoagulant, is formed in the body.
•Heparin is made by theliver,lungs, and other tissues in the body
and can also made in the laboratory.
•Heparin is a mixture of natural sulphated mucopolysaccharides,
which is generally found in granules of mast cells.
•The biosynthesis ofheparinoccurs primarily in the endoplasmic
reticulum and Golgi apparatus of mast cells.
•A tetra saccharide linker is attached to a serine residue on a
core protein, serglycin, and then the d-glucuronic acid (1→4)
N-acetyl-d-glucosamine disaccharide units are added.

4. COMMERCIAL SOURCE OF HEPARIN
•Most of the globally important pharmaceutical heparin, is
extracted currently from porcine intestinal mucosa,
although some is still obtained from bovine sources, mainly
in South America.
•Extraction of the crude intestinal material yields
approximately 0.8 Kg per animal which, following an
extensive purification procedure provides typically 180–
260mg of Heparin from each animal.

5. CHEMISTRY OF HEPARIN
•Heparin is a heterogenic mixture of
sulfonatedpolysaccharidesmade from a 15-100 repeating
units ofD-glucosamine,D-glucuronic acid, andL-iduronic
acid. (monosaccharides)
•Commercial heparin is essentially a mixture of a number of
compounds with various chain lengths and ofmolecular
massesbetween 5000 and 30,000 daltons.
•Monosaccharidesthat form heparin are modified by
eitherN-acetyl, orN-orO-sulfategroups, and are joined
byglucosidebonds, thus forming polymers with different
chain lengths.

6. •The main monosaccharides that form heparin are
a)6-sulfate-2-desoxy-2-sulfamino-α-d-glucose (A),
b)2-sulfateα-l-iduronicacid (B),
c)2-acetamido-2-desoxyα-d-glucose (C),
d)β-d-glucuronic acid (D), and
e)α-l-iduronicacid (E).
•These sugars are present in commercial heparin in descending
order: (A) > (B) > (C) > (D) > (E).

7. •Because of the presence ofsulfonateandcarboxyl
groupsin the molecules, heparin is a strongly acidic
compound that is partially neutralized in the body by
substituting acidichydrogen atomsinsulphategroups
withsodium ions.
•One unit of heparin (the "Howell unit") is an amount
approximately equivalent to 0.002 mg of pure heparin,
which is the quantity required to keep 1 ml of cat's blood
fluid for 24 hours at 0 °C.

8. STRUCTURE OF HEPARIN

9. TYPES OF HEPARIN
•There are two types of heparin drugs comprising
a. UNFRACTIONATED HEPARIN (UFH),
also known as standard heparin
b. LOW MOLECULAR WEIGHT HEPARIN (LMWH).

11. MECHANISM OF ACTION
•Heparin catalyses the inactivation
of thrombin by AT-III, by acting as a
template to which both the
enzyme and inhibitor bind to form
a ternary complex.

14. PHYSIOLOGICAL FUNCTION
•Heparin's normal role in the body is unclear.
•Heparin is usually stored within the secretory granules
ofmast cellsand released only into thevasculatureat sites
of tissue injury.
•It has been proposed that, rather than anticoagulation, the
main purpose of heparin is defence at such sites against
invading bacteria and other foreign materials.

15. MEDICAL USE
•Heparin is generally used for anticoagulation for the following
conditions:
1.Acute coronary syndrome, e.g.,NSTEMI
2.Atrial fibrillation
3.Deep-vein thrombosisandpulmonary embolism
4.Cardiopulmonary bypassforheart surgery
5.ECMOcircuit forextracorporeal life support
6.Hemofiltration
•Heparin and its low-molecular-weight derivatives
(e.g.,enoxaparin,dalteparin,tinzaparin) are effective in preventing
deep vein thrombosis and pulmonary emboli in people at high risk.

16. REFERENCES
•https://www.sciencedirect.com/science/article/abs/pii/S0065231808600670
•https://www.slideshare.net/venkateshkolla73/heparin-42670554
•https://www.news-medical.net/health/Heparin-History.aspx
•https://www.nature.com/articles/s41598-019-39093-
6#:~:text=Introduction,sources%2C%20mainly%20in%20South%20America .
•https://journal.chestnet.org/article/S0012-3692(15)41331-5/fulltext
•https://www.slideshare.net/IbrahimOsman5/anticoagulant-therapy-
78457821
•https://en.wikipedia.org/wiki/Heparin#Heparin_structure
•https://www.sciencedirect.com/topics/chemistry/heparin#:~:text=Heparin%
20is%20a%20heterogenic%20mixture,masses%20between%205000%20and%2
030%2C000

17. THANK YOU