Exam 3- Anti-Thrombotics Flashcards
Primary hemostatic (4):
- Endothelial injury
- Adhesion
- Activation
- Aggregation
What does endothelial injury expose?
Collagen and Von Willebrande’s factor
What happens in the stage of adhesion?
Circulating platelets bind to vWF and collagen
What 4 things occur during activation of primary hemostasis:
- Shape change
- Thromboxane A2 (TXA2) release
- Granule release ADP and coagulation factors
- GP IIb/IIIa conformation change
What does anti-thrombotic therapy do?
Prevent thombosis
Promote bleeding
What should you monitor on patients who are bleeding? (6)
- Hb
- bloody stools
- melena
- hematuria
- bruising
- oozing from arterial or venous puncture sites
MOA of aspirin:
Inhibits platelet activation and aggregation but irreversibly inhibiting COX-1 which prevents conversion of arachidonic acid into thromboxane (platelet agonist and vasoconstrictor)
Clinical uses for aspirin 3:
Acute coronary syndrome
MI
Percutaneous coronary intervention
What kind of secondary prevention does aspirin have?
Stroke
TIA
PAD
CAD
What 2 additional things does aspirin have?
Antipyretic
Analgesic
4 adverse effects of aspirin:
Bleeding
GI upset
Anaphylaxis
Children develop Reye’s syndrome
4 P2Y12 receptor antagonists:
Clopidogrel
Prasurgrel
Ticagrelor
Cangrelor
Of the P2Y12 receptor antagonists, which one is IV only:
Cangrelor
MOA of clopidogrel and prasugrel:
Inhibits ADP-induced platelet activation and aggregation
-irreversibly inhibit ADP P2Y12 receptor
Compare clopidogrel and prasugrel:
Prasugrel is more potent and faster onset
MOA of ticagrelor and cangrelor:
Inhibits ADP-induced platelet activation and aggregation
-reversible inhibit ADP P2Y12 receptor
Compare ticagrelor and cangrelor:
Ticagrelor: twice daily administration
Cangrelor: continuous IV infusion
Clinical uses for P2Y12 preceptor antagonists (3):
Acute coronary syndrome
MI
Percutaneous coronary intervention
What secondary prevention does P2Y12 receptor antagonists have?
Stroke
TIA
PAD
CAD
Adverse effects of ticagrelor:
Dyspnea
When is prasugrel contraindicated?
In patients with history of stroke/TIA
MOA of GP IIb/IIIa inhibitors:
Prevent platelet aggregation
-bind to GP IIb/IIIa receptors and prevent formation of fibrinogen platelet to platelet cross links
Clinical uses for GP IIb/IIIa inhibitors:
Prevent ischemic compilations of percutaneous coronary intervention (PCI)
Adverse effects of GP IIa/IIIb inhibitors:
Hemorrhage
Thrombocytopenia
MOA of vorapaxar:
Inhibits thrombin-mediated platelet activation and aggregation by binding to the platelet protease-activated receptor-1 (PAR-1)
Clinical uses for vorapaxar:
Secondary prevention of ischemic heart disease after MI or PAD
Adverse effects of vorapaxar:
Increased risk of bleeding (life-threatening and fatal)
What are the 4 parenteral anticoagulants:
Unfractionated heparin
Low-molecular weight heparins (LMWH)
Fondaparinux
Direct Thrombin Inhibitors
MOA of unfractionated heparin:
Heparin interacts with antithrombin to change its conformation and enhance its ability to inactivate clotting factor protease, especially thrombin (IIa), IXa, and Xa
5 clinical uses for unfractionated heparin:
- Venous thrombosis (PE and DVT)
- Prevention of clotting in arterial and cardiac surgery
- Arterial fibrillation with embolization
- Prevent post-op DVT and PE after major abdominal-thoracic surgery
- Acute coronary syndrome or MI
Adverse effects of unfractionated heparin:
Hemorrhage
Heparin-induced thrombocytopenia (HIT)
-HIT is pro-thrombotic
MOA of low molecular weight heparins:
Interacts with antithrombin to inactivate clotting factors IIa (thrombin) and Xa
What do small size of heparin particles included in LMWH focus inhibition toward?
FXa
What do large heparin molecules are needed to inhibit:
Thrombin
Clinical uses for low molecular weight heparins:
Venous thrombosis (PE and DVT) Acute coronary syndrome or MI
Adverse effects of low-molecular weight heparins: (3)
Hemorrhage
Heparin-induced thrombocytopenia (HIT)
Epidural or spinal hematoma
Does unfractionated heparin or low molecular weight heparins have a lower risk of HIT?
Low-molecular weight heparins
MOA of fondaparinux:
Avidly binds antithrombin with high specificity, resulting in inactivation of factor Xa
Clinical uses of fondaparinux: (3)
Venous thromboembolism
Post-op venous thromboembolism
Anticoagulation with HIT
Adverse effects of fondaparinux: (3)
Hemorrhage
Does not cross react with HIT antibodies
Epidural or spinal hematoma
MOA of direct thrombin inhibitors:
Directly bind and inhibit unbound and fibrin-bound thrombin
Clinical uses for direct thrombin inhibitors: (2)
Argatroban (treat pts with HIT)
Bivalirudin (treat pts undergoing coronary angioplasty)
Adverse effect of direct thrombin inhibitors:
Hemorrhage
3 oral anticoagulants:
Warfarin
Dabigatran
Direct factor X inhibitors
MOA of warfarin:
Prevent reductive metabolism of inactive form of Vit K to its active form by Vit K reductase
-Active Vit K is needed for production of function clotting factors 2, 7, 9, 10 as well as endogenous anticoagulant protein C and S
Clinical uses for warfarin (2)
Venous thromboembolism
Thromboembolic complications with atrial fibrillation and/or cardiac valve replacement
Adverse effects of warfarin (3)
Fatal or non-fatal bleeding
Necrosis of skin
DO NOT use with pregnancy
MOA of dabigatron:
Active prodrug that inhibits thrombin that prevents development of thrombus
-serine protease that enables the conversion of fibrinogen to fibrin during the coagulation cascade
Clinical uses for dabigatran (2)
Venous thromboembolism
Thromboembolic complications associated with atrial fibrillation
Adverse effects of dabigatran (2)
Fatal or non-fatal bleeding
Dyspepsia
3 drugs that are direct factor X inhibitors:
Apixaban
Edoxaban
Rivaroxaban
MOA of direct factor X inhibitors:
Competitively inhibits free and clot bound factor Xa (needed to activated thrombin)
Clinical uses for direct factor X inhibitors (3)
- Venous thromboembolic events (VTE) with replacements
- Prevent stroke and systemic embolism with no valvular atrial fibrillation
- Treat DVT and PE
Combo of what with aspirin is used to reduce risk of major CV event in pts with chronic CAD or PAD
Rivaroxaban
Adverse effects of direct factor X inhibitors:
Fatal or non-fatal bleeding
How is oral aspirin effective if it has a high first pass metabolism?
All blood goes through portal quickly within 15 minutes
What is problem with ibuprofen and aspirin?
Ibuprofen can block aspirin from doing its job since aspirin is irreversible and ibuprofen is
Would a drug that inhibits CYP 2C19 amplify or reduce clopidogrel antiplatelet effect?
Reduce cause this coverts into active form (metabolite)
Why does P2Y12 inhibitors cause sensation of dyspnea?
Increase neuronal signaling and increases conductivity of pulmonary vagal C-fibers
5 indications for thrombocytes:
- STEMI
- DVT
- Pulmonary embolism
- Acute ischemic stroke
- Acute peripheral arterial occlusion