Antiplatelet Drugs Flashcards
What is the enzyme that breaks down membrane lipids to create arachidonic acid?
Phospholipase A2
What are the two pathways arachidonic acid can enter? (Name the two enzymes)
Cyclooxygenase (eventually makes thromboxanes and prostaglandins)
Lipoxygenase
(makes leukotrienes)
Describe the methods of Platelet Aggregation Assays
Take a patient’s plasma and subject it to different factors (ADP, thrombin, TRAP (agonist), epi, 5HT, collagen, ristocetin). See how well the platelets aggregate (measured by light transmission)
What is the difference between a primary and secondary aggregation?
Secondary aggregations are irreversible. Primary aggregations are reversible.
Light granules contain?
Platelet Factor 4 )heparin cofactor)
Beta-thromboglobulin
PDGF
Dense granules contain?
ADP Serotonin Epinephrine Ca2+ Histamine
Aspirin
MOA
Blocks COX1 and COX2 enzymes through acetylation. Prevents formation of thromboxane, leading to anticoagulation.
Cyclooxygenase Inhibitors
Celecoxib
Selective for COX2, but do have some antiplatelet effects
List the ADP Receptor Inhibitors
Ticlopidine Clopidogrel Prasugrel Ticagrelor Cangrelor
What are the oral ADP receptor inhibitors? What is the only IV ADP receptor inhibitor?
Cangrelor is the only IV agent.
Ticlopedine, Clopidogrel, Prasugrel, and Ticagrelor are oral ADP receptor inhibitors.
The ADP receptor inhibitors are prodrugs that require metabolic transformation EXCEPT for…
Ticagrelor
Cangrelor
Which ADP receptor inhibitor tends to have a high variability in patient response? If a patient is resistant to that drug, which drug should you substitute with?
Clopidogrel has high variation in patient response (30% inactivity)
Use Prasugrel if a patient is not responding to clopidogrel
Dipyridamole
MOA
Coronary vasodilator
Cilostazol
MOA and Indication?
Phosphodiesterase inhibitor used in intermittent claudication
What are the GP IIb/IIIa inhibitors?
Abciximab
Tirofiban
Eptifabatide
What is the thrombin receptor inhibitor? (Very new drug)
Vorapoxar
Aspirin
Mechanisms of Resistance
Mainly due to a mutation in COX2 enzyme.
The resistance may cause recurrent ischemic events in patients who are on aspirin.
ADP Receptor Inhibitors
MOA
Block the ADP receptor on the surface of platelets, blocking the upregulation of GP IIb/IIIa receptors in platelet activation/aggregation
Which antiplatelet drug is used in every dual/triple antiplatelet therapy?
Aspirin is used everywhere!
May be used with clopidogrel (block ADP receptors), GP IIb/IIIa inhibitors, Dipyridamol (coronary vasodilator), Cilostazol (phosphodiesterase inhibitor)
Antiplatelet Drugs Clinical Applications
- Cerebrovascular disease
- TIA
- Complete stroke - Coronary artery disease
- Acute MI
- Unstable Angina - Saphenous vein coronary artery bypass grafts
- Peripheral vascular disease
- Venous thrombosis
- Peripheral arterial disease (PAOD, intermittent claudication) - Small Vessel Disease
- TTP - Prevention of thrombus formation on artificial surfaces
Drug Interactions with Antiplatelet Agents
Which interactions can cause increased bleeding?
Thrombolytic agents (urokinase, streptokinase, TPA)
Heparin
Warfarin
Antithrombin agents (hirudin, bivalirudin, argatroban)
Aspirin blocks the conversion of AA to…? Where?
Thromboxane in the platelets. Low dose aspirin does not inhibit production of prostacyclins in the endothelium because it does not get through the thicker endothelial wall.
Which drug is an inhibitor of lipoxygenase?
Zileuton
Used in management and treatment of asthma
List two leukotriene antagonists
Montelkast - asthma and seasonal allergies
Zarirlukast- asthma treatment
Fish Oil Pharmacology
Mechanism of antiplatelet action
Omega 3 Fatty Acids (alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid)
Inhibit thromboxane A2
Lead to production of thromboxane A3, which is inactive in platelet action
