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KISHAN SINGH
M.PHARM (Pharmacology)
GLAIPR MATHURA
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Coagulation is the process whereby blood forms clots to
repair vascular injury and prevent blood loss.
 Excessive coagulation can lead to vascular
obstruction.
 Poor coagulation can lead to increased bleeding.
 Anticoagulation drugs inhibit the action of
coagulation factors- heparin or interfere with the
synthesis of coagulation factors(like vitamin K
antagonist, such as warfarin)
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 anticoagulant is a substance that prevents
coagulation; it stops blood from clotting. A
group of pharmaceuticals called anticoagulants
can be used in vivo as a medication for
thrombotic disorders.
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ANTICOAGULANT

1. Direct Thrombin Inhibitors
2a. Indirect Thrombin Inhibitors
2b. Coumarins
3. Fibrinolytic Drugs
4. Anti-Platelet Agents
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HIRUDIN
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Hirudin
is a naturally occurring peptide in
the salivary glands of medicinal
leeches that has a blood
anticoagulant property.
This is fundamental for the leeches’
alimentary habit of hematophagy,
since it keeps the blood flowing
after the initial phlebotomy
performed by the worm on the
host’s skin.
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Class I: Direct Thrombin Inhibitors

Hirudin
Present in leech saliva. Hirudin irreversibly binds to thrombin.
Purpose of leeches are used:
1. Improve circulation.
2. leeches are used to remove bad blood from vein.
3. Hirudin stays in circulation after leeches have been removed
reducing the chance of clot formation, and allowing the wound
to continue to bleed.
3. Bactericidal Effect
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 leech secreted a powerful anticoagulant, called
Hirudin.
 Hirudin is made up of 65 amino acids.
 These amino acids are organized into a compact N-
terminal domain containing three disulfide bonds
and a C-terminal domain which is completely
disordered.[
 Natural Hirudin contains a mixture of various
forms of the protein.
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 blood coagulation is the conversion of
fibrinogen into fibrin by the serine protease
enzyme thrombin
 Thrombin is produced from prothrombin, by
the action of an enzyme prothrombinase, in the
final stage of coagulation.
 Fibrin is then cross linked by factor XIII to form
a blood clot
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 The principal inhibitor of thrombin in normal
blood circulation is antithrombin III. Similar to
antithrombin III, the anticoagulation activity of
Hirudin is based on its ability to inhibit the
pro-coagulant activity of thrombin.
 Hirudin is the most potent natural inhibitor of
thrombin.
 antithrombin III Hirudin binds and inhibits
only the activity of thrombin forms with a
specific activity on fibrinogen.
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 Hirudin prevents or dissolves the formation of clots
and thrombi (i.e. it has a thrombolytic activity)
 Hirudin has advantages over commonly used
anticoagulants and thrombolytic like heparin, it not
interfere with the biological activity of other serum
proteins and can also act on complexed thrombin.
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 It is difficult to extract large amounts of Hirudin
from natural sources, so a method for producing and
purifying this protein using recombinant
biotechnology has been developed.
 Marketed preparation of Hirudin :-
Lepirudin (Refludan®)
Desirudin (Revasc/Iprivask®).
Several other direct thrombin inhibitors are derived
chemically from Hirudin.
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Heparin
Heparin discovered by Maclean in 1916 by a second
year medical student at johns Hopkins hospital
This was name heparin ,because it was first extracted
from liver
Heparin is not a single substance it is a mixture of
sulfated mucopolysacharides
Its molecular weight is 10000-40000
It present together with histamine in the granules of
mast cells
Commercial preparations are obtained from beef lung
and pig intestinal mucosa .
Heparin antagonist is protamine sulfate
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 Heparin is a naturally-occurring
anticoagulant produced by basophiles
and mast cells to prevent formation
and extension of blood clots
 Heparin does not disintegrate clots
that have already formed. It permits
the body's natural clot lysis
mechanisms, i.e. Fibrinolytic
 As the thrombokinase is released, it
neutralizes the action of heparin to
allow clotting to occur
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Adverse Effects:
 Increases bleeding because it inhibits blood clot
formation.
 Risk of bleeding can be mitigated by close
monitoring.
 heparin is contraindicated in patients with: active
bleeding; haemophilia; ulcerative lesions of
gastrointestinal tract; recent surgery in the brain.
 Heparin overdose is managed by discontinuing the
drug, and if bleeding occurs: administer protamine
sulphate which combines with heparin to form a stable
ion pair complex (inactivated).
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 Heparin is given by injection or drip into a vein
intravenously or by subcutaneously
 Heparin works by inhibiting the three major clotting
factors (thrombin, thromboplastin, and prothrombin)
 It slows the process of thromboplastin synthesis,
decelerates the conversion of prothrombin to thrombin,
and inhibits the effects of thrombin on fibrinogen,
blocking its conversion to fibrin.
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 Low-molecular weight heparin is gradually
replacing heparin for treatment of most
patients with venous thromboembolism
and acute coronary syndromes because it
has more convenient and cost-effective
 It has similar results to heparin
 Administered by subcutaneous
injection
 Examples of LMWH:-
lovenox® tinzaparin, certoparin,
parnaparin, reviparin and
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 LMWH is obtained by alkaline degradation of
heparin benzyl ester
 LMWH molecules are enriched with short chains
with higher anti-Xa: IIa ratio
 Low molecular weight heparins (LMWHs) are
fragments of standard unfractionated heparin (UH)
formed by depolymerisation by different methods of
manufacture. The heparinoid, danaparoid,
is a mixture of heparin

 Less inhibition of platelet function
 potentially less bleeding risk, but not shown in
clinical use
 Lower incidence of thrombocytopenia and
thrombosis
 less interaction with platelet factor 4
 fewer heparin-dependent IgG antibodies

 No need for laboratory monitoring
 Higher bioavailability - 90% vs 30%
 Longer plasma half-life
 Decreased “heparin resistance”
pharmacokinetics of UH are influenced by its bindings to
plasma protein, endothelial cell surfaces, macrophages, and
other acute phase reactants

COMPLICATIONS OF THERAPY
 bleeding more with uf than lmw heparin
 osteoporosis
 thrombocytopenia
 rapid clearance of lipoproteins
 hypersensitivity reactions
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UF HEPARIN
SHORTER HALF LIFE
LMW HEPARIN
LONGER HALF LIFE
LOWER & LESS RELIABLE
BIOAVAILABILITY
ANTI-Xa : ANTI-
THROMBIN
ACTIVITY
S/C INJECTION
8-12 HOURS
HIGHER &MORE
RELIABLE
BIOAVAILABILITY
ANTI-Xa : ANTI-
THROMBIN
ACTIVITY
S/C INJECTION
ONCE / 24 HOURS
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 Coagulation is the process whereby blood forms clots to
repair vascular injury and prevent blood loss.
1. Direct Thrombin Inhibitors
Example: Hirudin
Binds directly to the active site/substance recognition site of
thrombin, preventing the enzyme from converting
fibrinogen to fibrin.
Indication: Heparin Induced Thrombocytopenia; Acute
Coronary Syndrome.
2a. Indirect Thrombin Inhibitors
Example: Heparin
Anticoagulant that works by indirectly inhibiting thrombin
and other clotting factors by increasing the activity of
antithrombin.
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