ANTIPLATELETS, ANTICOAGULANT,

THROMBOLYTIC

Antiplatelets:

Anticoagulants:

Drugs that prevent platelet adhesion, activation, and

aggregation
Drugs that prevent blood coagulation cascade
through modification of coagulation factors

Thrombolytics/ fibrinolytics:

Drugs that degrade the thrombus

Platelet activation:
Platelet activation
Thrombin, ADP, serotonin, thromboxane A2
Activation of receptors on platelet surface:
TxA2 receptor, ADP-receptor, Glycoprotein IIb/IIIa
receptor (fibrinogen receptor)

Platelet adhesion
Injured endothelium releases von Willebrand
factor (collagen receptor)

Platelet aggregation
Linking of platelet by fibrinogen
3

PLATELET ACTIVATION

ANTI PLATELETS
1. ASPIRIN: Inhibitor of cyclooxygenase
AA ------------ Thromboxane-A2
COX

Aspirin irreversibly blocks COX-1 in the platelet

TxA2 Prevent platelet activation by TxA2
Also inhibits formation of PGs in gastric mucosa
irritation
Should be given immediately in acute coronary
syndrome (UAP, MCI)
Life long use in all ischemic vascular disease
(coronary, cerebral, peripheral)
Some patients show aspirin resistance
5

ANTI PLATELETS
2. ADP-receptor blockers: (Thienopyridine derivatives)
Ticlopidine
Permanent inhibition of ADP receptor inhibit activation of GP
IIb/IIIa receptor
Less gastric irritation than aspirin
Side effects: neutropenia, liver abnormalities, thrombotic
thrombocytopenia

Clopidogrel

Structurally similar to ticlopidine, Similar mechanism of action

Less side effects than ticlopidine, but much more costly
Prodrug: activated by CYP 3A4 to active form
Faster onset of action after loading dose
Slightly less GI adverse effects than aspirin
Now become standard therapy in ACS
Some patients show clopidogrel resistance
6

ANTI PLATELETS
GP IIb/IIIa RECEPTOR BLOCKERS (fibrinogen and vWF
receptor)
Abciximab (RheoPro)
Tiorofiban (Aggrastat)
Eptifibatide (Integrilin)

ANTICOAGULANTS
Heparine routinely used in all ACS
Unfractionated heparine (UFH)
Low molecular weight heparine (LMWH):
Fraxiparine, nadroparine, enoxaparine, dalteparine

Synthetic pentasaccharide: Fondaparinux

Mechanisms of action:
Binds to antithrombin inactivate of F Xa and F IIa.
Fondaparinux inactivate F Xa only

Kinetics
Should be administered parenterally (iv, sc)
UFH need monitoring of effects (aPTT)
LMWH & fondaparinux: no needs of aPTT
monitoring
LMWH & fonaparinux have a longer half life
once or twice daily
Do not cross placental barrier safe for
pregnant women
Antidote of heparine toxicity: Protamine sulphate

10

 Side effects
Bleeding
HIT (heparine-induced thrombopenia)

Contraindication
Active bleeding, haemophylia, severe
hypertension, intracranial hemorrhage,
advance hepatic or renal disease, threatened
abortion

11

Oral Anticoagulant
Warfarin, dicumarol
A vitamine K antagonist inhibits activation of
vit K-dependent factors (II, VII, IX, X)
Slow onset of action
Administered orally
Need monitoring of prothrombin time (INR)
Target: INR 1.5 3.5 of normal level (reduction
of PT by 25%)

12

Toxicity
Warfarin readily crosses placental barrier
hemorrhagic and malformation of the fetus
contraindicated during pregnancy
Rarely: cutaneous necrosis, infarction of the
breast, fatty tissues, intestines, extremities.
Interact widely with other drugs (NSAID, vit K,
barbiturates, rifampicin, diuretic, steroids,
sulpha, amiodarone, ) and foods
Antidote: Vit K
13

FIBRINOLYTIC (thrombolytic)

Main indication: reperfusion in New onset STEMI (< 6-8 h)

Side effects and contraindications

Side effects:
Hemorrhage
Hypotension (Streptokinase)
Allergic reaction (Streptokinase)

Contraindications

Active bleeding
Any previous history of hemorrhagic stroke
Non hemor. Stroke within 1 year
Internal bleeding within 6 mo.
Hypertension (>180/110)
Major surgery, trauma
Pregnancy
15