L33 Antiplatelet Drugs Flashcards
During platelet aggregation and release reactions, what happens?
Pharmacologically active substances are released from granules. In addition, many of the prostaglandin derivatives such as thromboxanes are formed.
Describe a platelet aggregation assay.
- Prepare PRP
- Activate platelets (ADP, TRAP, EPI, 5-HT, collagen, ristocetin, AA)
- Measure light transmittance (more aggregation, more light)
You are looking for indication of platelet dysfunction (lack of aggregation)
What is an antiplatelet agent?
A drug that decreases platelet adhesion, activation, and aggregation, thereby inhibiting thrombus formation
Where are antiplatelet agents effective?
In arterial circulation (where anticoagulants such as heparin and warfarin have little effect)
What are the 8 main antiplatelet agents/categories?
- Aspirin
- COX inhibitors
- Propionic acid derivatives (NSAIDs)
- ADP receptor inhibitors
- Dipyridamole (coronary vasodilator)
- Cilostazol (intermittent claudication)
- GP 2b3a inhibitors
- Prostacyclin analogues
What is the main COX inhibitor?
Celebrex
What are the main NSAIDs?
Ibuprofen, naproxen
What are the 5 major ADP receptor inhibitors?
Ticlopidine, Clopidogrel (Plavix), Prasugrel, Ticagrelor, Cangrelor
What are the 3 GP 2b3a inhibitors?
- Abciximab
- Tirofiban
- Eptifabatide
___ may be a cause of recurrent ischemic vascular events in patients taking aspirin.
Aspirin resistance
What may be the cause of aspirin resistance?
COX polymorphism
What is the MOA of ADP receptor inhibitors?
The drug binds to the ADP receptor on the platelet, preventing subsequent platelet aggregation
___ has high interpopulation variation.
Clopidogrel
What is the MOA of GP 2b3a inhibitors?
The drug binds to the GP 2b3a receptor and inhibitors platelet aggregation.
What are the # clinical applications of antiplatelet drugs?
- Cerebrovascular disease (transient ischemic attack, complete stroke)
- Coronary artery disease (acute myocardial infarction, unstable angina)
- Saphenous vein coronary artery bypass grafts
- Peripheral vascular disease (venous thrombosis, peripheral arterial disease)
- Small vessel disease (TTP)
- Prevention of thrombus formation on artificial surfaces
What are the important drug interactions with antiplatelet agents?
- Thrombolytic agents
- Heparin
- Warfarin
- Antithrombin agents
Describe the metabolism of arachadonic acid.
AA is released by phospholipase A2. It is then converted via COX to cycloendoperoxides and then to thromboxanes (platelets), prostacyclins (endothelium), and prostaglandins (smooth muscle)
OR
via 5-LO to leukotrienes
What is the MOA of aspirin?
Inhibition of COX, which inhibits thromboxane formation and inhibits platelet aggregation
What are the different effects caused by thromboxane and by prostacyclin?
Thromboxane: vasoconstriction and platelet aggregation
Prostacyclin: vasodilation and platelet disaggregatino
What is an inhibitor of lipoxygenase?
Zileuton (treatment of asthma)
What are 2 leukotriene antagonists?
Montelkast (asthma/seasonal allergies), Zaririukast (asthma)
What are the active ingredients in omega-3 fatty acids?
- Alpha-linolenic acid
- Eicosaphentaenoic acid
- Docosahexaenoic acid
What is the mechanism of fish oil?
Antiplatelet via membrane effects and thromboxane A3 (inactive) formation
What are the two phosphodiesterase inhibitors?
- Dipyridamole
2. Cilostazol
