The document discusses the coagulation process, highlighting the formation of blood clots through primary and secondary hemostasis, and the roles of various coagulation factors and platelets. It also provides an overview of anticoagulants, including heparin and newer agents, their mechanisms of action, and indications for use in conditions like strokes and heart attacks. Additionally, it addresses the importance of antifibrinolytics and other drugs that affect platelet aggregation.

1. Presented By,
ASWIN K
B.Pharmacy, Final Year,
KMCH College of Pharmacy.

2.  Coagulation is the process of conversion of
Blood from a liquid form into a gel form and
formation of a blood clot.
 Homeostasis is the process of Cessation of
blood loss from a damaged vessel and
followed by Repair.

3. CELLULAR (PLATELETS) PROTEIN (COAGULATION FACTOR)
 Activation
 Adhesion
 Aggregation of platelets
 Deposition and maturation of fibrin
By Activating,
 Factor I - fibrinogen
 Factor II - prothrombin
 Factor III - tissue thromboplastin
(tissue factor)
 Factor IV - ionized calcium ( Ca++ )
 Factor V - labile factor or proaccelerin
 Factor VI - unassigned
 Factor VII - stable factor or
proconvertin
 Factor VIII - antihemophilic factor
 Factor IX - plasma thromboplastin
component, Christmas factor
 Factor X - Stuart-Prower factor
 Factor XI - plasma thromboplastin
antecedent
 Factor XII - Hageman factor
 Factor XIII - fibrin-stabilizing factor

4.  Bleeding (hemorrhage or bruising)
 Obstructive clotting (thrombosis).

5.  Coagulation begins after injury to the Blood
vessel has damaged the Endothelium lining of
blood vessels.
Blood vessel Damage
Explosure of Blood to subendothelial
space
Explosure of subendothelial Tissue Factor to
Plasma factor VII &Change in Platelets.

6.  PRIMARY HEMOSTASIS:
Platelets forms a plug at the site of
injury is called primary hemostasis.
 SECONDARY HEMOSTASIS:
Additional coagulation factor/clotting
factors beyond Factor VII forms a Fibrin
strands to strengthen the platelet plug is
called secondary hemostasis.

7. Endothelium damage
Circulating platelets +underlying collagen
(via gp VI receptor)
Signal cascade &Activation of platelet Integrins
Tight binding of platelet to the extracellular matrix
Process of adhere platelet to the site of injury

8.  Activated platelets release ADP , Serotonin, PAF,
Platelet factor 4, Thromboxane A2.
 Activated platelets also activate other platelets.
 Activated platelets changes its shape from
Spherical to Satellite.
 Fibrinogen Cross-links between glycoprotein &
aggregation of adjacent platelets.

9. Activated platelet Release granular substances
Activate Gq-linked receptor
Increases the coc.of Calcium in the platelet’s cytosol
Activate protein kinase C
act
Phospholipase A2
Modify Integrin membrane glycoprotein &
Increases affinity to bind Fibrinogen

11. 1.Calcium & phospholipids:
Require for tenase & prothrombinase
complexes to function.
2.Vitamin K:
Gamma-glutamyl carboxylase
add
-COOH group to glutamic acid residues
(F,II,VII,IX,X Protein S,C,Z)

12. Vitamin K
Vitamin K epoxide reductase
Active form
Maturation of Clotting Factors

13. Protein C:
Thrombin Act on Protein C
Activated Protein C
APC Protein + S Phospholipid (Co factor)
Degrade Fva &FVIIIa

14. Serine protease inhibitor (serpin)
degrade
FIXa,Fxa,FXIIa,FXIIa

15.  Limit the action of TF
 Inhibit excessive TF-mediated activation of
FVII &FV

16. Plasminogen (plasma protein)
Tissue plasminogen activate(t-PA)
Plasmin
Fibrin Fibrin degrade product

17. Endothelium
release
PG I2
Activate
Gs protein – linked receptor
Adenyl cyclase
cAMP
Cytosolic Calcium level decreases

18.  It is the process of Desorption &
Reorganisation of Blood clot.

19.  Anticoagulants also called as blood thinners.
 These are chemical substances that prevent
or reduce coagulation of blood & prolonging
the clotting time.

21. Heparin also known as unfractionated heparin
(UFH).
HISTORY::
1. Heparin was discovered by Jay
McLean and William Henry Howell in 1916.
2. In 1918, Howell coined the term 'heparin' for
this type of fat-soluble anticoagulant.
3. In the early 1920s, Howell isolated a water-
soluble polysaccharide anticoagulant, which he
also termed 'heparin',
CHEMISTRY:
1. Native heparin is a polymer with
a molecular weight ranging from 3 to
30 kDa and commercial heparin
preparations is in the range of 12 to 15 kDa.
2. [Heparin is a member of
the glycosaminoglycan family
of carbohydrates and consists of a variably
sulfated repeating disaccharide unit
MOA:
Binds with antithrombin III
Inactivate thrombin,factor Xa and protease
ANTODOTE:
1.Protamine sulfate
(1 mg per 100 units of heparin that had been
given over the past four hours).
21MEDICINAL CHEMISTRY II

22.  Heparin (M.Wt- 5000 -40,000Da) is a
naturally occurring polysaccharide that
inhibits coagulation.
 LMWHs are defined as heparin salts having
an average molecular weight of less than
8000 Da
ANTIDOTE:
1.Protamine

23. AntiThrombin
(Serine protease inhibitor)
Degrade Activate
FIXa,Fxa,FXIIa,FXIIa
LMWHs
DRUGS:
1. Bemiparin
2. Nadroparin
3. Reviparin
4. Enoxaparin
5. Parnaparin
6. Certoparin

24. Vitamin
Vitamin K epoxide reductase
Active form
Block
Maturation of Clotting Factors
Vitamin K antagonists

25. Dicumarol
Phenindione
Coumarin
Warfarin
Ethyl Bicoumacetate

26. Fibrinogen
Thrombin
Fibrin (clot) Inhibit
DTI

27. Bivalent:
Bivalirudin
:
Hirudin
Bivalirudin
Lepirudin
Desirudin
Univalent:
Argatroban
Inogatran
Melagatran (and its
prodrug ximelagatran)
Dabigatran
Argatroban
ximelagatran

28.  These are a class of anticoagulant drugs which act
directly upon Factor X in the coagulation cascade,
without using antithrombin as a mediator.
 These compounds as substitutes for the currently
administered vitamin K antagonists or low
molecular weight heparin.
 ADVANTAGES:
1.Rapid onset and offset of action.

29. Rivaroxaban
Apixaban Edoxaban
DRUGS:
1.Rivaroxaban
2.Apixaban
3.Edoxaban
4.Darexaban
5.Eribaxaban

30. Fondaparinux
Idraparinux sodium
DRUGS:
1.Fondaparinux
2.Idraparinux sodium
3.Idrabiotaparinum

31.  These are agents which decrease platelet
aggregation and inhibit thrombus formation
 They are effective in the arterial
circulation, where anticoagulants have little
effect.

32.  Irreversible cyclooxygenase inhibitors
 Aspirin
 Triflusal
 Adenosine diphosphate (ADP) receptor inhibitors
 Cangrelor
 Clopidogrel
 Prasugrel
 Ticlopidine
 Phosphodiesterase inhibitors
 Cilostazol
 Protease-activated receptor-1 (PAR-1) antagonists
 Vorapaxar
 Glycoprotein IIB/IIIA inhibitors (intravenous use only)
 Abciximab
 Eptifibatide
 Tirofiban
 Adenosine reuptake inhibitors
 Dipyridamole
 Thromboxane inhibitors
 Thromboxane synthase inhibitors
 Thromboxane receptor antagonists

33. Aspirin
Trifusal
Ticlopidine
Clopidogrel
Tirofiban

34.  Antifibrinolytics are a class of medication that are
inhibitors of fibrinolysis.
 These drugs block the binding sites of the enzymes
or plasminogen respectively and thus
stop plasmin formation.
MECHANISM OF ACTION:
Plasminogen (plasma protein)
Tissue plasminogen activate(t-PA)
Plasmin
Block
Fibrin Fibrin degrade product
Anti Fibrinolytics
MEDICINAL CHEMISTRY II 34

35. 6-aminocaproic acid
Tranexamic acid
DRUGS:
1.Aminocaproic acid
2.Tranexamic acid (Cyclokapron)
3.Ethamsylate
4.Aprotinin

36.  Strokes – where a blood clot restricts the flow of
blood to your brain, causing brain cells to die and
possibly resulting in permanent brain damage or
death.
 Transient ischemic attacks (TIAs) – also called "mini-
strokes", these have similar symptoms to a stroke,
but the effects usually last less than 24 hours.
 Heart attacks– where a blood clot blocks a blood
vessel supplying your heart, starving it of oxygen and
causing chest pain and sometimes death.
 Deep vein thrombosis (DVT) – where a blood clot
forms in one of the deep veins in your body, usually
your legs, causing pain and swelling.
 Pulmonary embolism – where a blood clot blocks one
of the blood vessels around the lungs, stopping the
supply of blood to the lungs.

37. MEDICINAL CHEMISTRY II 37