DRUGS USED

TO AFFECT
BLOOD
COAGULATION
 Terminology:
-Bleeding time (1-6 min)
Thrombocyt Bleeding time

-Clotting time (6-10 min)

Deficiency factor intrinsic pathway)
Hemophilia ) Clotting time
Heparin )
-Prothrombine time: indicate the total prothrombine in
the blood

-Thrombus: unwanted clot inside a blood vessel

Red thrombus (venous thrombus) contains:
Fibrin web >>> Thrombocyt Erythrocyte
Occurs in slow flowing blood i.e.
-Deep vein thrombus (leg vein)
-Post operative thrombosis
-Atrial fibrilation
-Arrtificial heart valve
Venous thrombosis Pulmonary embolism

White thrombus (Arterial thrombus)

Occurs in fast flowing blood /high flow rate
It contain: Thrombocyt >>> fibrin >
Example:- Myocardial infarction
-Stroke
 Hemostasis
Is finely regulated dynamic process of:
-maintaining fluidity of the blood
-repairing vascular injury
-limiting blood loss
-avoiding vessel occlusion (thrombosis)

This lecture will discuss about the drugs used to limit

bleeding (coagulant) and those that inhibit thrombosis
(anticoagulants).
 ANTICOAGULANTS
ANTIPLATELET
(ANTITHROMBOTICS)
THROMBOLYTICS
COAGULANTS
 1-6

COAGULATION
Platelets and clotting factors are responsible
for initiating coagulation. When an injury
occurs, platelets (thrombocytes) immediately
migrate to the damaged area. Because platelets
stick to each other (aggregation) and to the
vessel walls (adhesion), they form a plug
around the injured tissue. Plasma clotting
factors reach the platelet plug and interact with
each other to form a stable blood clot.
Hemostasis is the balance between clot
formation and clot breakdown that occurs
throughout the day.
 27-7

The effects of Drug affecting

coagulation
Anticoagulants
Interfere with plasma clotting factors
Antiplatelets
Inhibit platelet aggregation
Thrombolytics
Disolved clot
-Coagulants
To limit bleeding
 1-8

Anticoagulants
The clinically useful anticoagulants
produce their pharmacological response
by interfering with plasma clotting
factors, inhibiting platelet aggregation,
or dissolving clots.
 1-9

WARFARIN
-Warfarin has a long onset and duration of
action because it takes days (1-3 days) to
clear the normal clotting factors before an
effect can be observed.
-Coumarin derivatives
-Orally active
-Only active in vivo
-Less active in arterial thrombosis
-MOA: block Vit K dependent gamma
carboxylation of glutamate
residuesmodified
factors VII,IX,X & prothrombin
-Enzyme inducer (barbiturate,Carbamazepine)
decrease the anticoagulant effects
-E. inhibitor (cimetidine,metronidazole)
increase the anticoagulant effects.
-antidote:-concentrate of clotting factors
-fresh frozen plasma
-Phytomenadione i.v. (onset:6-12 hrs)
Antiplatelet (Antithrombotic)
Aspirin:
-MOA:Inhibit synthesis of prostaglandin
Thromboxane A2 by irreversible
acetylation of cyclooxygenaseAggre-
gation thrombocyte (-)
-Dose :325 mg/d Indonesia 80 mg/d.

Clopidogrel & Ticlopidine.

-MOA:Irreversibly Block the ADP receptor
on platelet
Blockade of platelet Gp IIB/IIIA receptor:
-Abciximab i.v.
-Eptifibatide i.v. infusion
-Tirofiban i.v. imfusion

Dipyridamole
-Vasodilator
-MOA;inhibit adenosine uptake & cyclic
GMP phosphodiesterase activity.
Effect antiplatlet< combine with aspirin
or warfarin.
Fibriolytics/Thrombolytics
-Streptokinase (not an enzyme)
-MOA: Streptokinase + plasminogen
activator complex convert plasmino-
nogenplasmin thrombolysis.
-ADR:Allergic reaction.

Alteplase ; Reteplase ; Tenecteplase

recombinant DNA technology
Allergic reaction (+).
-Anistreplase = APSAC (anisoylated plas
minogen streptokinase complex
single i.v.
-Allergic reaction (+).
 27-15

Heparins
-Increase the formation AT-Thrombin complex
(1000 x normal)
-Heparin AT III complex inhibit factors IXa,Xa
XIa &XIIa.
-Heparin acts in vitro & in vivo
-Heparin administration: S.C./i.v. infusion
-Indication:deep vein thrombosis.M.I. & stroke
recovery
-DOA:4-6 hrs
-Antidote protamine sulphate i.v.
-Heparin = Indirect Thrombin Inhibitor (ITI)
-Heparin consists of UFH (unfractionated
heparin) &LMWH (low molecular weight hepa
rin ,e.g.enoxaparin,dalteparin,Tinzaparin).
-UFH monitoring: a PTT (activated Partial
Thromboplastin Time).
-ADR:Bleeding
HIT (heparin induce thrombocytopenia)
-Contraindication:Hypersensitivity
HIT
Active bleeding
 27-17

Monitoring Coagulation
Therapeutic dosage is maintained and
evaluated based on clotting time:
Partial thromboplastin time (PTT)
Prothrombin time (PT)
International normalized ratio (INR)
Activated partial thromboplastin time (APTT)

Drugs that affect platelet aggregation can

cause increased bleeding.
Warfarin has the greatest potential for drug
interactions.
 27-18

Clinical uses:
Heparin: Venous thrombosis and
pulmonary embolism
Warfarin:
Prophylaxis of venous thrombosis and
pulmonary emboli
Antiplatelets:
Coronary artery disease
Thrombolytics:
Dissolution of preformed clots
The future for anticoagulants
Molecular targets are factor IIa (thrombin)
and factor Xa
The two candidate compounds, one direct
thrombin inhibitor (dabigatran etexilate)
and one direct factor Xa inhibitor
(rivaroxaban) are hoping to be approved
as new oral anticoagulants in the near
future
 27-20

Coagulants/Hemostatics
Agents used to decrease the
severity of hemorrhage:
Vitamin K
Protamine sulfate
Aminocaproic acid
Tranexamic acid
Thrombin (cattle or DNA technology)
topical
Gelatin collagen or cellulose sponges