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
)
Heparin
)

Clotting time

-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.

The effects of Drug affecting

coagulation
Anticoagulants
Interfere with plasma clotting factors

Antiplatelets
Inhibit platelet aggregation

Thrombolytics
Disolved clot

-Coagulants
To limit bleeding

27-7

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 cyclooxygenaseAggregation 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 plasminonogenplasmin 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