Coagulant,Anticoagulants,Thrombolytics and Fibrinolytics.

1. 1
COAGULANT AND
ANTICOAGULANTS
Prepared by:
Prof. Mirza Anwar Baig
Anjuman I Islam's Kalsekar Technical Campus,School of
Pharmacy.
New Panvel,Navi Mumbai

2. 2
Topic Learning outcomes
1. Classification of drugs
2. Detail pharmacology
a)Mechanism of action
b)Therapeutic uses
c)Adverse effects
2

3. Classification of Coagulants
1. Agents acting locally eg: Thrombin
2. Transfusional agents
a.Human fibrinogn
b.Anti haemophilic globulin
c.Plasma or blood
3. Non transfusional agents
a.Vitamin K
b.Epsilon Amino Caproic Acid (EACA)
c.Tranexamic Acid
d.Ethamsylate
e.Aprotinin
f.Desmopressin
3

4. 4
1. Agents acting locally
a. Thrombin
Source: bovine/human plasma
Properties: Stable as dry powder, stored between 2 to
8 C. Inactive below pH 5.
Uses: Restricted to local application in oozing of blood.
b. Thromboplastin:
Source: Prepared from acetone extracts of brain/lung
tissue of killed rabbits.
Use: To dertermine prothombin time.
As a local haemostatic in surgery.
4

5. 5
c. Fibrin:
Source: obtained from human plasma
Uses:
1.It is used in dehydrated form as sheet to cover bleeding
surface.
2.Used in combination with thrombin to hold it over
bleeding area.
d.Gel foam :
It is porous, pressed form of gelatin sponge
Uses: Used in conjunction with thrombin to control oozing
of blood.
Completely absorbed may be left in place after suturing of
wounds.
Available as cones,packs, sponges and powders.
5

6. 6
e. Oxidized cellulose:
1.It is surgical gauze treated with nitrogen dioxide.
2.It promote clotting by a reaction between haemoglobulin and
cellulosic acid.
3.It becomes sticky when mixed with tissue juice and exert its
haemostatic action.
4.Absorbed within 2 to 10 days interfere with bone
regeneration.
f. Microfibrillar collagen:
Source: Prepared from bovine collagen.
Use: When applied to bleeding surface, attracts platelets to
form plug followed by natural clot.Used in capillary bleeding.
It is non allergic but can promote local infection and abscess
formation.
It is inactivated by autoclaving and hence should not be
sterilized.
6

7. 7
2. Transfusional agents:
a)Human fibrinogn
b)Anti haemophilic globulin
c)Plasma or blood

8. 8
a. Human fibrinogen:
Source: Human plasma
Uses:
1.It is used for restoring normal fibrinogen levels in haemorrhagic
complications caused by acute afibrinogenemia.
2.Fibrinogen and thrombin may be employed together for local
haemostasis.
b. Antihaemophilic globulin (AHG)
1.Haemophilia A and B (Christmas disease) are two commonest
hereditary haemorrhagic states. Due to deficiency of specific clotting
factor VIII and IX respectively.
2.Antihemophilic globulin or concentrate factor VIII is highly effective in
treatment of hemophilia A.
3.It is now prepared by DNA recombinant technique.
4.Half life is 12 hours.
5.Desmopressin increases AHG blood level by increasing its release.
8

9. 9
6. Are very expensive and may be associated with greater risk of
inducing IgG antibodies to factor VIII.
7. Probably act locally at the site of tissue injury.
8. Treatment should be guided by the physician experienced in the
case of hemophilia.
9.Christmas disease: fresh or stored plasma infusion is indicated to
replenish the factor IX which is stable on storage.
c. Plasma or Blood
i. Fresh frozen plasma is used in coagulation disorders as it
provides all clotting factors.
ii.Concentrated of factor VIII or preparation containing factors
II,VII,IX,X are also available for specific deficiencies.
iii.Whole blood transfusion is not preferable as it carries risk of
transfusion reactions.
9

10. 10
3. Non/ Transfusional agents:
a)Vitamin K
b)Epsilon Amino Caproic Acid (EACA)
c)Tranexamic Acid
d)Ethamsylate
e)Aprotinin
f)Desmopressin

11. 11
a. Vitamin K:
1.It comprises of 3 distinct fat soluable, naphthoquinone
compounds
2.Participate in biosynthesis of several clotting factors.
3. Vitamin K1 is found in several foods. fat-
soluable,Phytonadione (Phylloquinone)
4. Vitamin K2 is produced by bacteria in the GI T.
5. Vitamin K3 is synthetic compound.
Fat soluable: Menadione,Acetomenaphtone
Water soluable: Mendione sod.bisulfite. Menadione sod.Diphosphate.
Pharmacological actions:
i.Participate in carboxylation of the glutamic acid residues of
prothrombin and factors VII,IX,X in the final stage of synthesis.
ii.Also involve in electron transport (Coenzyme) and oxidative
phosphorylation.
11

12. 12
Absorption, fate and excretion:
a)Produced by the flora of human intestine.
b)Fat soluable vitamin K1 and K2 are absorbed in
presence of bile salts while water soluable K3
(Menadione) absorbed even in their absence.
Adverse reactions:
a)Rare after oral adminstration.
b)Serious anaphylactoid reactions after IV use.
c)Large doses of synthetic menadione produce haemolytic
anemia, hyper-bilirubinemia, kernicterus in new born.
d)Menadione competes with bile salts for glucuronide
detoxification causing accumulation of bile salts in blood
result in Juandice.
12

13. 13
Therapeutic uses:
1. Adult vitamin K deficiency: produced by
a. Malabsorption
b. Obstructive juandice
c. Prolonged malnutrition.
Menadione
used
2. Vitamin K deficiency in infants:
during acute diarrhoea.
3. Neonatal vitamin K deficiency:
4. Bleeding state during oral anticoagulant therapy
Vitamin K generally given orally but require bile salt
for absorption.
Menadione preparation are NOT used. May cause
adverse reactions in neonates with vitamin K deficiency.
Should be avoided in pregnancy to avoid haemorrhagic
disease.
13

14. 14
b. Epsilon amino caproic acid
1.Water soluble analogue of lysine.
2. Mechanism of action:
Inhibits plasminogen activation.
a)It is reversibly occupying lysine
binding Site on plasminogen.
b)Activation of plasminogen to plasmin
is Inhibited.
c)Result in inhibition of fibrin binding to
Plasminogen.
Hence inhibit fibrinolysis and stabilize the clot.
14

15. 15
ADME:
15
1.Orally absorbed
2.60 to 90% excreted in urine.
3.A blood level of 13mg/100 ml of blood required for
plasminogen inhibition.
4.130 mg/100 ml of blood required for inhibition of
plasmin activity.
ADVERSE EFFECTS:
Nasal stiffness, abdominal discomfort, dyspepsia,
hypotension, skin rashes etc.

16. 16
Therapeutic uses:
16
Used in prevention of hyper plasminaemic bleeding
state due to damage of tissues rich in plasminogen
activator.
For example
a.Primary menorrhagia
b.During prostatic surgery: contraindicated in hematuria
(risk of ureteral occlusion by un lysed clot)
c.Upper GI bleeding
d.Bleeding after dental extraction.
e.Bleeding associated with thrombocytopenia,
postpartum hemorrhage.

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c. Tranexamic acid (TA):
17
Derivative of lysine,10 time more potent & longer duration of
action than EACA .
Indications are similar to EACA.
Adverse effects are mild inlcude nausea,diarrhoea hypotension.
Both EACA and TA are contraindicated in patients with
subarachnoid bleeding because they may induce vasospasm and
ischemic stroke.
d. ETHAMSYLATE:
1. Used for similier indication as EACA and TA.
2. Probably act by correcting abnormal platelet aggregation ,does
not stabilize fibrin.

18. 18
e. Aprotinin:
18
It is polypeptide obtained from bovine lungs.
Mechanism of action:
1. It inhibits the action of several proteases like plasmin,trypsin,
chymotrypsin, kallikrein by forming reversible enzyme-inhibitor
complex.
2. By binding to plasmin, aprotinin prevents the degradation of fibrin
and fibrinogen (COAGULANT EFFECT).
3. Prevent plasmin-induced degradation of platelet glycoprotein 1b,
hence preserve platelet activity (COAGULANT EFFECT).
4. In addition, at higher doses aprotinin also inhibits tissue and plasma
kallikrein HENCE inhibits activation of Factor XII (responsible for
synthesis of thrombin), would decrease the amount of thrombin
(Powerful platelet aggregator) generated, (WEAK ANTICOAGULANT
EFFECT)
5. Hence inhibit initiation of both coagulation and fibrinolysis.
6. Was used in cardiac surgery to reduce blood loss.
Withdrawn from Market
Because of cardiovascular toxicity,stroke and renal toxicity.

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f. Desmopressin:
19
Analogue of arginine Vasopressin.
(antidiuretic,vasocontrictor,analgesic)
Increases for short time plasma concentration of
factor VIII in hemophiliacs and von willebrand factor
(required for platelet adhesion) in von Willebrand
disease. (Treatment of choice)
Therapeutic uses:
It shortens or normalize bleeding time in patients
with congenital defects of platelets.
Acquired bleeding during uremia or use of aspirin.
Acute variceal bleeding.

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g.Conjugated estrogen:
20
1.It improves platelets functions,shorten the prolonged
bleeding time.
2.Compared to desmpressin it has a delayed onset but
much longer duration of action.
3.Can be combined with desmopressin for synergestic
effect.
h. Vitamin C:
Specifically control bleeding due to scruvey.
i. Snake venome:
(copper head and russel viper)
Enhances coagulation by stimulating thrombokinase.

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ANTICOAGULANTS
21
CLASSIFICATION
1. Used in invivo
A. Parenteral anticoagulants (Fast acting):
Eg; Heparin,Bivalirudin,Dabigatran, Heparinoids
B. Oral anticoagulants (Slow acting)
i. Coumarin derivatives eg. Bishydroxycoumarin etc
ii. Indandione derivative eg. Phenindione
2. Used in invitro
A. Heparin
B. Calcium complexing agent eg. Sodium citrate

22. 22
A. Parenteral anticoagulants (Fast acting):
Heparin
22
1. Heparin was discovered in 1916 by Mclean, a medical
student.
2. It is naturally occurring anticoagulant, mole.wt is 5000-
3000 daltons.
3. Found in granules of mast cells, abundant in liver and in
lungs.
4. Commercial heparin is obtained from lungs and intestinal
mucosa of pigs and cattle.
5. It composed of mucopolysaccharides composed of number
of sulfated D-glucosamine and D-glucuronic acid linked
together through oxygen bridge.
6. The high content of esterifies sulfuric acid makes heparin
strongly electronegative compound.
7. Anticoagulant activity is attributed to its strong
electronegative charge.

23. 23
Pharmacology of heparin:
23
1. Blood coagulation:
i.Prevent clotting of blood in vitro and invivo.
ii.Act on all the three stages of coagulation.
iii.It activates antithrombin III which then inactivate
IXa and Xa & thrombin.
iv.AT-Heparin complex is 1000 time
active inhibitor than AT alone.
v. The binding of heparin with AT
Changes the confirmation of AT
vi. Thus AT-Heparin complex easily
Bind to serine protease of Xa.
(atleast 5 saccharide of heparin are
essential)

24. 2424
vii.Attachment of heparin antithrombin complex to thrombin
requires at least 18 saccharide units.
viii.Formation of fibrin thus prevented.
ix.Small dose of heparin have much less antithrombin activity
but inhibit factor Xa (a critical moiety of coagulation).
x. Small dose is used s.c for prophylaxis.
xi.Prolong clotting time 2 to 2.5 times.
2.Effect of lipoprotein lipase:
Activate the lipoprotein lipase and abolishes the cloudiness
of the hyper lipemic plasma (Tyndall effect).
3.Antiplatelet:
Inhibit platelet aggregation and prolong the bleeding time.
4.Miscellaneous actions:
Inhibits aldosterone secretion and causes hyperkalemia.
Have some antiinflammatory actions.

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ADME:
25
1.Poorly absorbed orally.
2.Well absorbed after SC injection.
3.When given exogenously taken up by mast cell and act like
a storage depot.
4.Metabolized by liver by heparinase.
5.Heparin does not cross placental barrier and is not
secreted in milk.
Adverse reactions:
Rare anaphylactic reactions
Bleeding: avoid aspirin during heparin therapy
Thrombocytopenia: due to platelet aggregation and formation of
heparin dependent antiplatelet antibodies. Improves after
discontinuation of therapy, platelet counting before the start of
therapy and during the therapy is recommended ,Stop the therapy
if platelet count is below 100000/cmm

26. 26
Low molecular weight heparins
26
Obtained by fractionation of native heparin.
Molecular weight between 4000-65000.
Advantages over native heparin are:
1.Absorbed more uniformly than native heparin
2.Have longer duration of action t1/2= 4
3.Selectively inactivate factro Xa: their activity for
thrombin is minimal.
4.Have predictable anticoagulant effect
5.Interact relatively less with platelets: fewer bleeding
episodes.
6.Less antigenic: less frequently causes thrombocytopenia
& osteoporosis.

27. 2727
Disadvantages :
Are expensive
LMW heparins vary in their pharmacokinetic properties.
Examples:
Enoxaparin, dlateparin,tinzaparin,pamaparin,reviparin.
Native heparin still remains the parenteral anticoagulant of
choice in ICU,operation theatre,patients with renal impairment.
Fondaparinux:
oSynthetic polysaccharide,binds to antithrombin.
oEnhances inactivation of factor Xa.
oT1/2 is 17 hrs
Small doses of heparin given SC for prophylaxis,have to
monitored whole blood clotting time & activated partial
prothromboplastin time .
No blood sample monitoring for LMW Heparin

28. 28
Heparin antagonist (HA):
28
HA is a strongly basic compounds which reacts with strongly
acidic groups of heparin. Thereby abolishing anticoagulant
activity.
Protamine Sulfate:
1.Mixture of simple,low molecular weight polypeptide
2.Found in fish sperm.
3.Binds firmly to heparin and inactivate it.
4.1mg of protamine neutralizes 100 units of heparin activity.
5.After protamine injection patient should be observed for
recurrence of bleeding as protamine sulfate is also a
anticoagulant.
6.Protamine IV may cause fall in BP,bradycardia,dyspnoea.
7.It partially neutralizes LMWH.

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Other Factor Xa inhibitors:
Rivaroxaban:
29
1.It is orally active,direct selective factror Xa inhibitor.
2.Used for prevention and treatment of arterial and
venous thromboembolism.
3.Does not require monitoring.
Danaparoid:
oObtained from porcine intestinal mucosa.
oGiven SC twice a day, for prophylaxis.
oDoes not cause thrombocytopenia,has no antidote.
oUsed as heparin substitute to prevent postoperative
DVT.

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Hirudine (Direct acting thrombin inhibitor)
30
1. Potent antithrombin polypeptide
2. Obtained from leech hirudo medicinalis
3. Now been synthesized by recombinant DNA technique.
4. Unlike heparin, it binds irreversibly to thrombin.
5. It inactivates free as well as fibrin-bound thrombin.
6. It doesn’t require antithrombin or other co-factor.
7. It not only prevents conversion of fibrinogen to fibrin but
also blocks thrombin catalyzed platelet aggregation and
activation of other clotting factors.
8. Its activity is monitored by same tests as of heparin.
9. No antidote available.

31. 3131
Bivalirudin:
1.Analogue of hirudin, with rapid onset and offset (due to
reversible action).
2.Safer than latter.
Argatroban:
1.Reversible direct thrombin inhibitor
2.Alternative to hirudin.
Dabigatran:
It is prodrug (Dabigatran etexilate), orally active, direct
inhibitor,
As effectvie as enoxaparin,ADR are same as enoxaparin.
Major adv: orally active without the need of coagulation
monitoring.
All direct thrombin inhibitors are used in patients
with or at risk of developing heparin induced
thrombocytopenia.

32. 32
Human antithrombin concentrate:
32
Prepared from human plasma.
It is used alone or in combination with heparin to treat patients with
rare hereditary disorder antithrombin III deficiency.
B. Oral anticoagulants (Slow acting)
1. COUMARIN DERIVATIVES (SLOW ACTING)
Effective orally (contrast to heparin)
Bis hydroxy coumarin or dicumaral (first coumarin compound)
Most commonly used drug is WARFARIN SODIUM
Anticoagulant action:
1. Vitamin K epoxide (inactive) convert to vitamin K reduced (active)
by vitamin K epoxide reductase.
2. Vitamin K (active) carboxylate the clotting factors II,VII,IX,X (active)
3. Oral anticoagulant competes with vitamin K and inhibit vitamin K
epoxide reductase.
4. Slow acting: becz of long half life of clotting factors.
5. Increase plasma antithrombin level

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ADME:
33
1. Slow oral absorption, crosses placenta and secreted in
milk.
2. Action is slow, because they prevent the formation of
essential clotting factors by liver but do not destroy
the already circulating factors.
Adverse effects:
Bleeding:
Fetal toxicity
Cutaneous gangrene

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Warfarin sodium:
34
1.It is employed as RAT POISON.
2.It is racemic mixture.
3.Its advantages over coumarin (dicumaral /Bis
hydroxycoumarin) are
i. It is almost 99% orally absorbed
ii. Rapid onset of action
iii. Adverse effects are few, may inculde alopecia,
urticaria, dermatitis.
iv. Can cross placenta but not secreted in milk (long
term warfarin use should be avoided in pregnancy).
v. Major drawback is multiple drug interactions.

35. 35
Mechanism of action: Warfarin
35

36. 36
Drug interactions:
36
1.Inhibiting the platelet functions
(aspirin,NSAID)
2.Stimulating hepatic microsomal
catabolism of warfarin
(Barbiturates,rifampicin,carbamazepine).
3.Displacing warfarin from protein binding
(Sulfonamides,phenylbutazone,chlorpropa
mide etc)
4.Inhibiting metabolic clearance of warfarin
(cimetidine,omeprazole,amiodarone)

37. 37
Indandione derivatives:
37
These examples are PHENINDIONE,ANISINODIONE.
Anticoagulant activity is similar to coumarin compounds.
They are now OBSOLETE because of toxicity.
IN VITRO ANTICOAGULANTS
Physical methods:
By cooling the blood
Use of Paraffin,collodion or silicone coated Pan for collection
Calcium complexing agents:
Oxalates and Citrates: Potassium oxalate precipitate serum calcium
as calcium oxalate and form calcium sodium citrate.
The anticoagulant solution (B.P) contains 2.5 % sodium citrate in
0.9% saline.
Potassium oxalate produces convulsions hence not used in vivo.

38. 3838
EDTA: (Ethylene di amine tetra acetic
acid)
Chelating agent having greater affinity for
calcium.
Its sodium salt is used.
Heparin: Discussed earlier

39. 39
Thrombolytics or Fibrinolytics
1. Streptokinase
2. Recombinant tissue type plasminogen activator
3. Urokinase
4. Acylated plasminogen/ streptokinase activator

40. 40
Mechanism of Fibrinolysis:
All thrombolytic agents are directly
or indirectly plasminogen activator.
CLASSIFICATION:
1. Fibrin specific thrombolytic agents
Alteplase,Reteplase,Tenecteplase
2. Fibrin non-specific thrombolytic
agents
Streptokinase, Anistreplase,
Urokinase.
All are directly acting
thrombolytic agent except
Steptokinase.
Pharmacokinetic profile,patients
tolerance and disease state will
be consider to select the
thrombolytic agent.
40

41. 4141
Streptokinase:
1.Obtained from Beta haemolytic Steptococci group C.
2.It is inactive as such: BUT when combines with
plasminogen,the plaminogien-STC complex is ACTIVE.
3.Causes conversion of plasminogen to plasmin.
4.Antistreptococcal antibodies of past infection inactivate
it.
5.It may cause hypersensitivity reactions and anaphylaxis.
6.Fever,hypotension and arrhythmias are reported.
7.Used in DVT, due to availability of other fibrinolytics it
is not used in developed countries.
8.Being least expensive still widely used in developing
countries.

42. 42
Urokinase:
42
1. Obtained from human urine.
2. Now obtained from cultured human renal cells
3. Potent direct plasminogen activator
4. It is non-antigenic,non-pyrogenic,non -allergic. (differ
from STC).
5. Lacks fibrin specificity and very expensive.
6. Its use is followed by heparin and latter oral
anticoagulants.
7. Used to lyse fibrin or blood deposit in anterior
chamber of eye.
8. Used in patient in whom STK has been used for an
earlier episodes.
9. Limited use because of availability of newer
fibrinolytics.

43. 43
Alteplase
(Recombinant plasminogen activator)
1. Produced by recombinant DNA technology from human tissue
culture.
2.Specifically activates gel phase plasminogen already bound to
fibrin, and has little action on circulating plasminogen.
3.It is rapidly cleared by liver and has a plasma t1/2 of 4 to 8
min.
4.Because of the short t1/2, it needs to be given by slow IV
infusion and often requires heparin coadministration.
5.It is nonantigenic, but nausea, mild hypotension and fever
may occur.
6.It is expensive.

44. 44
Rateplase:
1. It is modified form of rt-PA, longer acting.
2. somewhat less specific for fibrin bound plasminogen.
3. The longer duration of action enables bolus dose
administration (10 mg over 10 min repeated after 30
min).
Tenecteplase:
1. It is a mutant variant of rt-PA with higher fibrin
selectivity and longer duration of action.
2. The clinical efficacy and risk of bleeding with
reteplase and tenecteplase are similar to alteplase.

45. 45
Uses of fibrinolytics:
1. Acute myocardial infarction
2. Deep vein thrombosis
3. Pulmonary embolism
4. Peripheral arterial occlusion
5. Stroke

46. 46
Antiplatelet agent

47. 47
Process of Platelet Plug formation...
Damage to vascular endothelium Release of reactive
proteins like collagen
and von Willebrand factor (vWF)
React respectively with
platelet GPIa, and GPIb receptors
Platelets are activiated
Release of proaggregator.
and vasoconstrictor mediators (TXA2,
ADP and 5-HT)
The platelet GPIIb/III, receptor undergoes a
conformational change favouring binding with
fibrinogen
Induces platelet aggregation and platelet plug is formed

48. 48
Control of intravascular thrombus formation:
In veins, due to sluggish blood flow, a fibrinogen tail is formed
which traps RBCs "the red tail'. (Anticoagulants are more
effective in venous thrombosis)
In arteries platelet mass is the main constituent of the thrombus.
(Antiplatelet drugs are more useful in arterial thrombosis).
Prostacyclin (PGI2), synthesized in blood vessels,(strong inhibitor
of platelet aggregation).
A balance between TXA2, released from platelets and PGI2
released from vessel wall appears to control intravascular
thrombus formation.
Platelets also play a role in atherogenesis.

49. 49
AntiplateletAntiplatelet agentagent::
1. Prostacyclin PGI2
2. Inhibitor of TXA2 formation: asprin
3. ADP receptor antagonist: Ticlopidine,Clopidogrel
4. Phosphodiesterase inhibitor: Dipyridamole
5. Glycoprotien IIb/IIIa antagonist: Abciximab

50. 50
Physiology of platelet aggregation:

51. 51
Role of vWF and Gp receptors:

52. 52
Mechanism of action of antiplatelet agents:

53. 53
Prostacyclin (PGI2)
It is naturally produced
by endothelial cells of
blood vessels.
Effects: causes
vasodilation,inhibitig
platelet aggregation.
Uses: during hemodialysis
and to treat pulmonary
hypotension.
Very unstable,short half
life of 3 mints.

54. 54
TXA2 inhibitor: Aspirin
In low dose selectively
inhibit synthesis of
TXA2,higher dose
also inhibit
prostacyclin formation.

55. 55
Uses of Aspirin:
1. Decreaseg the incidence of CHD.
2. Preventing MI in patients with angina.
3. Acute cronary syndrome where immediate platelet
inhibition is desirable.
4. Patients undergoing cronary bypass surgery.
5. Preventing stroke in CVD.
6. Preventing ischemic limb complication.
7. Preventing reinfarction in pateints having MI.
8. Preventing pre eclampsia in pregnant women but should
be given between 12th to 16th weeks of pregnancy.
9. In hypertensive patients it is avoided.
10.Can cause G.I Bleeding.

56. 56

57. 57
Dazoxiben:
1. It is substituted imdiazole.
2. Selectively blocks production of TXA2.
3. Without affecting PGI2.
4. ASPRIN IS SAFER AND FAR SUPERIOR.
Ticlopidine: (ADP receptor antagonist)
1. Thienopyridine derivative.
2. Active metabolite is ADP antagonist.
3. Oral onset of action delayed for hours.
4. Slightly more effective than aspirin but more toxic than
aspirin.

58. 58
ClopidogrelClopidogrel: (: (ADPADP receptorreceptor antagonistantagonist))
1. Chemically related to ticlopidine.
2. Irreversibly block P2Y12 receptor present on
platelet responsible for platelet aggregation.
3. As compare to aspirin it is more expensive.
4. Combination with aspirin is synergestic only for
acute complications.
5. Combination may give excessive bleeding.
6. Alternative P2Y12 antagonists are developed with
fast onset of actions like newer Thienopyridines
(Prasugrel, Ticagrelor,cangrelor.)

59. 59
Dipyridamole:Dipyridamole:
(Phosphodiesterase inhibitor)(Phosphodiesterase inhibitor)
 It is vasodilator.
 Reversibily inhibit platelet phosphodiestrase
enzyme. leading to increase in cAMP. Decrease
in cystosolic calcium and inhibit platelet
aggregation.
Use:
 As adjuvant to warfarin in patients with
artificial heart valves.

60. 60
Glycoprotien IIa/IIIb antagonist:
1. A monoclonal antibody against the platelet
receptors eg: Abciximab
2. Synthetic inhibitor eg: Tirofiban (competative
blocker of receptor)
Abciximab:
have synergestic effect with aspirin and
heparin. effect last for 48 hrs.
Tirofiban and Eptifibatide: competative inhibitor.
plasma half life is 2to 2.5 hrs.