A-29. Drugs used coagulation disorders I: Antiplatelet agents.

Question 1

TXA2 Synthesis Inhibitors

Answer 1

Acetylsalicylic acid (aspirin)

Question 2

P2Y12 Receptor (ADP receptor) Antagonist

Answer 2

Clopidogrel, prasugrel, ticagrelor

ticlopidine, cangrelor

Question 3

PAR-1 Antagonist

Answer 3

Vorapaxar

Question 4

GpIIb/IIIa (vWF/fibrinogen receptor) Antagonist

Answer 4

abciximab, eptifibatide, tirofiban

Question 5

PDE Inhibitors

Answer 5

dipryidamole and cilostazol

Question 6

Antiplatelet drugs are used for arterial or venous thrombotic disorders?

Answer 6

Arterial thrombotic disorder

Question 7

MOA of Acetlysalicylic Acid

Answer 7

• Irreversible inhibition of COX enzyme

- Decreased synthesis of both TXA2 (platelet activator/aggregator) and prostacyclin (platelet/vasodilator)

Question 8

Where is TXA2 and prostacyclin formed?

Answer 8

TXA2 is formed in platelets, which doesn’t synthesize new COX once it is inhibited.
Prostacyclin is formed by endothelium which synthesizes new COX.

Question 9

Indications of Acetylsalicylic Acid

Answer 9

1. ) Primary/Secondary Prophylaxis of Arterial Thromboemboli
   - As in unstable angina, MI, angioplasty, cerebrovascular issues
2. ) Pain, fever, inflammation

Question 10

Loading dose of acetylsalicyclic acid

Answer 10

250-500 mg given acutely

Question 11

Kinetics of Aspirin

Answer 11

Good oral absorption, high plasma protein binding, first pass metabolism to salicyclic acid in liver

Question 12

Side effects of Aspirin

Answer 12

Bleeding, peptic ulcers

Question 13

P2y12 inhibitors (thienopyridines) MOA

Answer 13

non-competitive inhibition of P2Y12- an ADP receptor on platelets

Question 14

P2y12 inhibitor kinetics

Answer 14

Prodrugs activated in the liver (except ticagrelor and cangrelor)
Good oral absorption
High protein binding
Have a good synergistic effect with other anti-platelet drugs
Ticagrelor and cangrelor are reversible inhibitors which do not require activation by CYP enzymes

Question 15

Indications of P2Y12 inhibitors

Answer 15

cardio/cerebrovascular disorders

Question 16

Side effects of P2Y12 inhibitors

Answer 16

1. ) GI upset and minor bleeding

2. ) Leuko-/thromboctopenia- rare, worse with ticlopidine (regular CBCs for 1st three months)

Question 17

P2Y12 inhibitors interactions

Answer 17

CYP2C19 inhibitors i.e. omeprazole, fluoxetine, fluconazole inhibit clopidogrel activation

Question 18

PAR-1 Antagonist (Vorapaxar) MOA

Answer 18

Inhibits platelet PAR-1 (protease-activated receptor) leading to decreased platelet activation by thrombin

Question 19

Kinetics of PAR-1 Antagonist (Vorapaxar)

Answer 19

Good oral absorption; metabolized by CYP enzymes

Question 20

Indications of of PAR-1 Antagonist (Vorapaxar)

Answer 20

1. ) Myocardial Infarction- as secondary prophylaxis

2. ) Peripheral Arterial Thrombi- in combination with aspirin

Question 21

Contraindication of PAR-1 Antagonist and side effect

Answer 21

bleeding (contraindication and side effect), TIA, and stroke

Question 22

GPIIb/IIIa Receptor Antagonist (Abciximab) MOA

Answer 22

high affinity mAB against GpIIb/IIIa receptor complex causing irreversible antagonism of vWF.fibrinogen binding by GpIIb/IIIa
(also binds endothelial cells and vitronetin receptors)

Question 23

Kinetics of abciximab

Answer 23

IV admin; short metabolic (30 min) but lon biological half-life (18-24 hours)

Question 24

Indications of abciximab

Answer 24

PCI procedures for treatment of acute coronary syndrome

Question 25

Side effects of abciximab

Answer 25

1. ) Bleeding- major bleeding in 4%; severe bleeding may require platelet transfusion
2. )Thrombocytopenia- in 1%; monitor platelet counts
3. )hypotension, bradycardia, nausea, vomiting

Question 26

Eptifibatide and tirofiban are both _______ antagonists of GpIIb/IIIa
kinetics

Answer 26

competitive antagonist

Given via IV; short 2-4 hours duration of action; more thrombocyte-selective than abciximab

Question 27

Dipyridamole
MOA
Indication
Complications

Answer 27

PDE and adenosine uptake inhibition leading to vasodilation and platelet inhibition
Indication: Heart valve thrombus prophylaxis- only effective with warfarin
Complications: coronary steal syndrome with high IV doses
-healthy coronaries dilate while stenotic ones already at max dilation do not leading to coronary circulation is stolen by already-healthy vessels

Question 28

Cilostazol is used for?

Answer 28

Newer PDE inhibitor for the treatment of intermittent claudication

Question 29

Antiplatelet drugs may skew which test?

Answer 29

Bleeding time is increased