Drugs for Coagulation

Question 1

Triggers of Clot Formation

Answer 1

1. Endothelial injury
2. Blood stasis
3. Presence of foreign material

Question 2

Platelet migration aggregation

Answer 2

Factors:
1) Proaggregants (TXA2, ADP, 5-HT)
2) Antiaggregants (PGE1, PGI2 (Prostacyclin), cAMP)
3) Receptors:
* GPIa - binding of platets to collagen
* GPIb - binding to Von Willebrand Factor (VWF)
* GPIIb / GPIIa - for interplatelet binding through fibrinogen bridge

Question 3

Activation of blood coagulation cascade (clotting factors)

Answer 3

Goal: activate clotting factor I (fibrinogen) to form factor Ia (fibrin), which is its stable form

2 Pathways involved:
* Extrinsic (Factors VII, III)
* Intrinsic (Factors VIII, IX, XII, XI)

Product:
* Secondary hemostasis / red thrombus
* Stabilized clot

Question 4

Regulatory Mechanisms

Answer 4

1. Antithrombin-III (AT-III)
   * endogenous anticoagulant (inhibits FIIa)
2. Protein C & S
   * endogenous anticoagulant
3. Plasmin
   * serine protease
   * activated from plasminogen via tPA

Question 5

1st line in the primary & secondary prevention of acute thrombotic events (Antiplatelet)

Answer 5

Aspirin

Question 6

MOA of Aspirin

Answer 6

Irreversible acetylation of COX & blocks synthesis of PGI2 and TXA2

Question 7

Aspirin Uses

Answer 7

Prevention of thrombosis
Prevention of second attack of MI

Question 8

Aspirin selectively inhibit synthesis of TXA2 in

Answer 8

Low Doses

Question 9

Adenosine Diphosphate Inhibitors

Answer 9

Irreversible Blockers
Clopidogrel
Prasugrel
Ticlopidine

Reversible Blockers
Cangrelor
Ticagrelor

Question 10

MOA of ADP Inhibitors

Answer 10

Inhibits platelet ADP P2Y12 receptors → Decrease GP2b, GP3a receptor activation, thus no platelet aggregation

Question 11

A/Es of Ticlopidine

Answer 11

Neutropenia
Thrombocytopenia (monitoring of WBC and platelets weekly for 3 months)

Question 12

Alternative to ASA in stroke prophylaxis

Answer 12

Clopidogrel

Not associated with neutropenia & thrombocytopenia

Question 13

Coronary vasodilator and a weak antiplatelet drug

Answer 13

Dipyridamole

Question 14

MOA of Dipyridamole

Answer 14

Blocks platelet uptake of Adenosine, activating Adenosine A2 receptor and increases cAMP
Inhibits Phosphodiesterase 3, inhibiting degradation of cAMP

Question 15

Uses of Dipyridamole

Answer 15

Vasodilator in myocardial perfusion imaging (Thallium Imaging)
Stroke prevention

*Can cause coronary steal phenomenon

Dipyridamole is in combination with Aspirin

Question 16

Antiplatelet and vasodilator

Answer 16

Cilostazol

Question 17

Inhibits phosphodiesterase 3 (PDE3) → Decrease cAMP degradation

Answer 17

Cilostazol

Question 18

Treatment of intermittent claudication, limb pain and weakness

Answer 18

Cilostazol

Question 19

Management of acute thrombous post angioplasty

Answer 19

Glycoprotein 2b, 3a Antagonist
* Abciximab
* Tirofiban
* Eptifibatide

MOA: Inhibits platelet aggregation by interfering with GPIIb/IIIa bindin

Question 20

First platelet GP 2b, 3a antagonist to be developed

Answer 20

Abciximab

Question 21

Antiplatelet which is a derivative of tyrosine

Answer 21

Tirofiban

Question 22

Cyclic heptapeptide from rattlesnake venom

Answer 22

Eptifibatide

Question 23

Protease-activated receptor 1 (PAR-1) antagonist

Answer 23

Vorapaxar

For patients with history of MI

Question 24

Anti-Platelet

Answer 24

A. TXA2 Synthesis Inhibitor
* Aspirin

B. ADP Inhibitors
* Clopidogrel
* Prasugrel
* Ticlopidine
* Cangrelor
* Ticagrelor

C. Phosphodiesterase Inhibitors
* Cilostazol
* Dipyridamole

D. GPIIb / GPIIIa Inhibitor
* Abciximab
* Eptifibatide
* Tirofiban

E. PAR-1 Antagonist
* Vorapaxar