Shared Flashcard Set

Details

Antiplatelet Drugs
Antiplatelet drugs
37
Pharmacology
Professional
11/06/2011

Additional Pharmacology Flashcards

 


 

Cards

Term
What are Platelets?
Definition

Anuclear cell fragments

 

Term
Where do platelets come from and how long do they live?
Definition

Originate from megakaryocytes in bone marrow

 

life span: 10 days

 

Normal Lab Value: 150,000-450,000 /µL

Term
What is the major trigger for all thrombotic events?
Definition
Atherosclerosis
Term
What are the 3 steps of how a platelet functions?
Definition

Initiation

Activation

Aggregation

Term
Components of platelet initiation....
Definition

Underlying disease (weakened surface easy to break)

 

Endothelial injury (exposes collagen, vWF, tissue factor)

 

von Willebrand factor (in endothelial- important for binding)

 

GP Ib receptors (on platelets- important for binding)

Term
Platelet activation begins with an agonist binding to platelet receptors to start the cascade. What are the potent and weak agonists for this process?
Definition

Potent Agonist

Adhesion to collagen after vascular damage

Adhesion to elements after plaque rupture

Thrombin


Weak Agonists

ADP

TXA2

Epinephrine

Term
After agonists bind to activate platelets, what actions does the cascade of signaling events result in?
Definition

1. Shape Change

2. Granule Release

3. Thomboxane A2 generation

4. Glycoprotein IIb/IIIa Receptor Activation

Term
All of the agonist/cascade events are linked to what type of protein?
Definition

G-Protein coupled Receptors

 

Platelets are activated by Gq, Gi, and G12/13 families

 

Platelets are inhibited by Gs pathways

Term
What are granules?
Definition

Granules are released after platelet activation.

 

initiated by binding of agonists to platelets.

 

3 types: alpha, dense, and lysosomal

Term
What is the major COX metabolite producted by platelets?
Definition
TXA2
Term

T/F

The final step in platelet activation is GP IIb/IIIa Receptor expression and activation

Definition

TRUE

This is the final step of platelet activation.

 

Increased expression on platelet surfaces

confromational change in the structure allows fibrinogen to bind

Term
What is the final step in platelet funtion?
Definition

Platelet Aggregation

 

Fibrinogen binds to activated GPIIb/IIIa receptors

 

A hemostatis plug of platelets meshed in fibrin is formed

Term
Indications for Antiplatelet Agents....
Definition

1. Cerebrovascular accident

2. Acute coronary syndrome

3. Angina

4. Vascular disease

5. Coronary artery bypass graft

6. Percutaneous coronary intervention

Term
What are the antiplatelet agents?
Definition

1. Aspirin

2. Thienopyridines

3. GP IIb/IIIa

4. Phosphodiesterase inhibitors

Term
What are the thienopyridines?
Definition

Ticlopidine (Ticlid)

Clopidogrel (Plavix)

Prasugrel (Effient)

Term
What are Abciximad, Eptifibatide, and Tirofiban?
Definition
GP IIb/IIIa antagonists
Term

T/F

 

Aspirin is a reversible inhibitor of platelets?

Definition

FALSE

 

Aspirin IRREVERSIBLY binds to platelets

 

Aspirin covalently inhibits platelets by transferring its acetyl group (acetylation)  to inhibit COX-1

Term
Why are low doses of ASA effective?
Definition

1. Inhibition of platelet COX-1 occurs at lower doses than vessel wall COX-2

 

2. Platelets have no nucleus

Term
What are the ADRs of aspirin?
Definition
GI upset, bleeding
Term
Onset and duration of action for aspirin?
Definition

Onset- 5 minutes (enhanced by chewing)

 

Duration- days

Term
MOA of Thienopyridines?
Definition

 Irreversible antagonists of platelet ADP receptors

 

 

Term

T/F

 

Thienopyridines are pro-drugs

Definition

TRUE

 

All need to be converted the the active form in vivo

 

This leads to their delayed onset of action

(max effect 3-5 days)

 

and many drug interationas

Term
Clopidogrel binds irreversibly to the ADP P2Y12 receptor to inhibit....
Definition

1. Platelet signaling events

2. Platelet granule release

3. GP IIb/IIIa receptor activation

4. Platelet aggregation

Term
What is the onset and duration of Clopidogrel?
Definition

Onset:

Initial response- 2 hours

Peak response- 3-7 days

Loading dose lowers time to onset

 

Duration:

Single dose- 72 hours

Multiple dose- 5-8 days

Term
What leads to variability in Clopidogrel?
Definition

1. Compliance

2. Pharmacokinetics

3. Drug Drug interations

4. Down regulation or upregulation of important platelet signaling pathways

5. Genetic polymorphisms - CYP450

Term
Stategies to minimize Clopidogrel variability:
Definition

1. increase clopidogrel dose

2. use alternative agents that produce greater inhibition

Term
Who is Prasugrel different than Clodidogrel
Definition
Prasugrel activations is a rapid single step process
Term
What is the newest ADP receptor antagonist?
Definition
Ticagrelor
Term
What is Ticagrelor used for?
Definition

Considered more efficacious for acute coronary syndromes than clopidogrel

 

NO activation required

Little inter-patient variability

Term
How does Ticagrelor differ from the other thienopyridines?
Definition

Reversibly binds platelet P2Y23

No metabolic activation

Term
What is Cangrelor?
Definition

Investigational antiplatelet agent

 

reversible P2Y12 antagonist

 

IV- onset within minutes

 

Plasma half life- 3 hours

Effects reversed quickly with stopping infusion

May be optimal for PCI setting

Term
MOA of GP IIb/IIIa receptor antagonists
Definition
Inhibits binding of fibrinogen to the activated GP IIb/IIIa receptor to prevent platelet aggregation
Term
What are the three GP Antagonists
Definition

Abciximab- monoclonal antibody

Eptifibatide- reversible RGD mimetic peptide

Tirofiban- reversible, non-peptide RGD mimetic

 

Peptides with specific sequence of fibrinogen to bind to receptor BUT doesn't illicit response

Term
What are GP antagonists used for?
Definition

Prevent ischemic events in PCI

 

Used in combo with clopidogrel

 

 

Term
Main ADR of GP antagonists
Definition
Bleeding
Term
Explanations of why GP antagonists failed at PO administration
Definition

1. Inappropriate dose or dosing regimen

2. lack of sufficient therapeutic window

3. may increase platelet activation

Supporting users have an ad free experience!