12-1: 1/6 - Antiplatelets

Front 1

Antiplatelet Therapy:
Indication
Timing

Back 1

Indication: Arterial thrombosis

Timing: Tx of existing thrombosis and prevention of recurrence

Front 2

How do prostacyclin and thromboxane control platelet aggregation and vasoconstriction.

Discuss cAMP levels.

Back 2

BV endothelial cells release prostacyclin

Prostacyclin causes BV RELAXATION; increases cAMP in platelets and decreases aggregation.

Platelets release Thromboxane A2 (TXA2) inducing BV constriction

Decreases cAMP in platelet and increases aggregation

Front 3

ADP Receptor Inhibitors:
MOA

Back 3

ADP rel'd by activated platelets and amplifies platelet activation.
These drugs inhibit ADP-induced platelet aggregation and degranulation.

Front 4

Ticlopidine:
Drug Class
Indications
AEs

Back 4

Thienopyridine derivative; blocks ADP receptors on platelets, thus inhibiting platelet agg and degranulation.

Indications:
Unstable angina
TIA
Stroke
Stents

AEs:
Nausea, dyspepsia, diarrhea

Front 5

Clopidogrel:
Drug Class
Indications

Back 5

Thienopyridine derivative
IRREVERSIBLY blocks ADP receptors

Indications:
Acute Coronary Syndrome
Atherosclerotic prophylaxis (pts w/CVA, MI, PAD)

Front 6

This drug irreversibly binds platelet ADP receptors.

Back 6

Clopidogrel

Front 7

What did the CAPRIE trial demonstrate?

Back 7

Clopidogrel is slightly better than ASA in preventing MI and strokes.

Front 8

These drugs are associated with TTP.

Which is more likely to cause TTP?

What must you do to prevent this?

Back 8

Ticlopidine and Clopidogrel

More cases reported with ticlopidine.

Must check platelets weekly when initiating drugs (mostly occurs within first month of starting drug)`

Front 9

What is the most potent platelet agonist? What are its receptors?

Back 9

Thrombin = most potent platelet agonist

Receptors = PAR-1, PAR-3

Front 10

ASA:
MOA
Dosing (for efficacy)

Back 10

Irreversible COX-1 inhibitor in platelets; limits arachadonic acid generation and thus inhibits TXA2 secretion.

Dosing: effective when used long-term in doses 50-100 mg/day

Front 11

PDE Inhibitors:
MOA

Back 11

Inhibit cAMP breakdown in platelet, thus increasing levels of cAMP in platelet.

Front 12

Dipyridamole:
Drug Class
MOA

Back 12

PDE-inhibitor

Inhibits adenosine uptake and cyclic nucleotide PDE, thus increasing cAMP levels in platelet by inhibiting cAMP degradation.

Front 13

GPIIb/IIIa Inhibitors:
MOA

Back 13

GPIIb/IIIa receptor mediates aggregation, on inactivated platelet receptor is in inactive form.

Thus, antagonizing the receptor will lead to inhibition of platelet aggregation.

Front 14

Abciximab:
Drug Class

Back 14

Short term GPIIb/IIIa receptor inhibitor

Rapid onset

Not specific for GPIIb/IIIa receptors

Front 15

Eptifibatide:
MOA
Indications

Back 15

Blocks GPIIb/IIIa receptors, preventing binding of fibrinogen and inhibiting platelet aggregation

Indications:
Acute Coronary Syndrome
Prevent thrombosis during angioplasty
MI, angina

Front 16

Tirofiban:
Indications

Back 16

Small molecule GP IIb/IIIa inhibitor

Indications:
Acute Coronary Syndrome
Unstable angina
MI

Front 17

This drug reduces risk of death and MI within first 7 days when combined with heparin.

Back 17

Tirofiban

Front 18

This drug has >10% risk of thrombocytopenia when used repeatedly.

Back 18

Abciximab