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Flashcards in antiplatelet drugs Deck (55)
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antiplatelet drugs inhibit what functions

primary hemostatic plug formation, aggregation, activation and release mechanisms.


Platelet Aggregation Assay

1. prepare PRP
2. activate platelets (PRP+ ADP, TRAP, epinephrine,
5-HT, collagen, ristocetin, AA)
3. measure Light transmittance (low= no aggregration, high = aggregation)


Light (alpha) granule release products:

a. Platelet factor 4 (aka heparin co-factor)
b. Beta-thromboglobulin
c. Platelet-derived growth factor (PDGF)


Dark (beta) granule release products:

a. Ca+2
b. Serotonin


Products formed during platelet activation and endothelial interaction:

prostaglandin derivatives, endoperoxides, thromboxanes.


advantages of antiplatelet drugs vs heparins and anticoagulants

These drugs are effective in the arterial circulation, where anticoagulants such as heparin and oral anticoagulants have relatively little effect.


types of antiplatelet drugs

1. Aspirin
2. Cyclooxygenase (COX) inhibitors (COX1 and COX2 inhibitors)
3. Propionic acid derivatives (NSAIDs)
4. ADP Receptor inhibitors
5. Dipyridamole (Persantine®) a coronary vasodilator
6. Cilostazol (Pletal®) – used for the management of intermittent claudication
7. GPIIb/IIIa Inhibitors
8. Prostacyclin analogue (Iloprost®)


what drugs belong to the ADP Receptor inhibitors group

Ticlopidine (Ticlid),
Clopidogrel (Plavix),
Prasugrel (Effient),
Ticagrelor (Brilinta) and
Cangrelor (Kengreal)


which drugs belong to GPIIb/IIIa Inhibitors group

abciximab, ReoPro®;
tirofiban, Aggrastat®, and
eptifabatide, Integrilin®


Dipyridamole (Persantine®) MOA

coronary artery dilator (used for coronary artery surgeries)


Aspirins MOA

COX-1 and COX-2 inhibitor


aspirins dosing for antiplatelet effects

Aspirin is used as a single low dose 81 mg/daily for antiplatelet actions


aspirin resistance

many pts do no respond to the normal daily dose of 81 mg per day leading to theurapeutic failure. Increasing the dose can restore the antiplatelet effect.

may be the cause of recurrent ischemic vascular events in patients taking asprin.

may be due to COX polymorphism


clopidogrens MOA

selectively inhibits ADP binding to its platelet receptor, preventing subsequent platelet aggregation


clopidogrel vs. Prasugrel

both inhibit platelet aggreation.
clopidogrel has a large amount of variation in responses within the population while prasurgrel has less variation and is therefore effective for a larger % of people.


Dual Antiplatelet Therapy

Aspirin/ADP receptor inhibitors
Aspirin/GP IIb/IIIa inhibitor


Triple Antiplatelet Therapy

Aspirin/ADP receptor inhibitor/ Cilostazol

not commonly used


GP IIb-IIIa inhibitors MOA

after platelets are activated they express GP IIb/IIIa, the GP IIb/IIIa inhibitor binds to the active site preventing fibrinogen from binding


clinical uses for antiplatelet drugs

1. Cerebrovascular disease:
a. Transient ischemic attack (TIA)
b. Complete stroke

2. Coronary artery disease:
a. Acute myocardial infarction
b. Unstable Angina

3. Saphenous vein coronary artery bypass grafts:

4. Peripheral vascular disease:
a. Venous thrombosis
b. Peripheral arterial disease (PAOD, intermittent claudication)

5. Small vessel disease
a. **Thrombotic thrombocytopenic purpura

6. Prevention of thrombus formation on artificial surfaces


Drug Interactions with Antiplatelet Agents

Thrombolytic agents (urokinase, streptokinase and tissue plasminogen activator).
2. Heparin/LMW Heparin/oral anticoagulants
3. Warfarin
4. Antithrombin agents (hirudin, bivalirudin and argatroban).

all increase the antiplatelet effect and risk of bleeding


Arachidonic Acid is released from

membrane phospolipids


Arachidonic Acid is used to make

Leukotrienes, Thromboxanes, Prostacyclins, Prostaglandins

aspirin and NSAIDs block thromboxanes, prostacyclins, and prostaglandins


arachidonic acid is metabolized by which 2 pathways

Cyclooxygenase pathway
-Prostaglandins, thromboxanes, prostacyclins

Lipoxygenase pathway
- Leukotrienes


Cyclooxygenase Pathway

Cycloxygenase represents constitutive (COX-1) and inducible (COX-2) enzymes.

Aspirin inhibits both COX-1 and COX-2 thereby limiting the production of prostaglandins.

In particular, thromboxane formation in platelets is inhibited.

This is the main mechanism by which aspirin mediates its therapeutic effects.


what participates in the Regulation of Prostacyclin and Thromboxane Synthesis

A. * Endothelial lining
B. * Lipoproteins and other blood components
C. Diet
D. Drugs
E. Hemodynamic factors


Lipoxygenase Pathway

A. Leukotrienes (SRSA)
Inhibitors of lipoxygenase
Zileuton (ZYFLO) –used in maintenance treatment of asthma
Leukotriene antagonists
- Montelkast (Singulair)- used in treatment of asthma and seasonal allergies
- Zarirlukast (Accolate, Accoleit and Vanticon) used in the treatment of asthma

this is the anti-inflammatory pathway. Drugs that affect this pathway are used for respiratory disease


prostacyclin effects

vasodilation, inhibits platelet aggregation

not affected by aspirin as much bc aspirin does not penetrate the endothelial cells


thromboxanes effects

vasoconstriction, promotes platelet aggregation

inhibited by aspirin


active ingredients in fish oil

A. α-linolenic acid
B. eicosapentaenoic acid
C. docosahexaenoic acid


Mechanism of antiplatelet action of fish oil

A. Membrane effects
B. Thromboxane A3 (inactive) formation - the acids compete with arachidonic acid in the prostaglandin pathway and are converted to thromboxane A3