16. Drugs used in coagulation disorders I: Antiplatelet agents

Question 1

COX-inhibitors

Answer 1

Irreversible inhibition of cyclooxygenase enzyme in platelets leading to reduce Thromboxane A2 release, which again will reduce stimulatory effect of platelet aggregation.

• Aspirin (acetylsalicylic acid)

Question 2

Glycoprotein IIb/IIIa inhibitors

Answer 2

Reversible inhibition of GP IIb/IIIa, which results in prevention of cross-linking of platelets with fibrinogen.

• Abciximab (monoclonal antibody, IgG)
• Eptifibatide (cyclic peptide)
• Tiro fiban (non-peptide)
• These are only given in the hospital by IV!

Question 3

ADP receptor antagonists

Answer 3

Irreversible inhibition of platelets ADP receptor (P2Y12 receptor, Gi-coupled), leading to decreased platelet aggregation.

• Clopidogrel (prodrug, activated by hepatic CYP450)
• Prasugrel (^ same as clopidogrel)
• Ticlopidine (older variant)
• Ticagrelor (newer drug, no activation required. Its also reversible)

Question 4

Phosphodiesterase inhibitors

Answer 4

Inhibits BOTH phosphodiesterase and adenosine reuptake (by endothelial cells), this will result in increased cAMP, which has an inhibitory effect on platelets.

Dipyridamole
- used after valve replacement
- used in combo w/ Aspirin to prevent ischemic stroke
Side effects: headaches, palpitation, flushing

Cilostazol (has vasodilating properties)
- treat intermittent claudication in patients w/ peripheral artery disease

• Both are given orally, and are contraindicated in heart failure!