Pharm: Antithrombotics Flashcards
Describe thrombi that form in the arteries vs. the veins.
Arteries:
lots of platelets, little fibrin, white thrombi
Veins
low platelets, lots of fibrin, red thrombi
Name and describe the 3 steps in platelet plug formation.
- Platelet Adhesion: Von Willebrand Factor on endothelium binds to glycoprotein 1-b on platelets
- Platelet Activation and Secretion: production of serotonin, ADP, and platelet-derived growth factor. Also secretion of Thromboxane A2 for PG synthesis.
- Platelet Aggregation: platelets bind to each other using fibrinogen to link glycoprotein IIb-IIIa receptors.
Activation of platelets causes the expression of the glycoprotein IIb-IIIa for plug formation. What are the two biggest stimulants for platelets to express this receptor?
Thrombin: produced in the blood in response to endothelial injury
Collagen: exposed due to endothelial injury.
Test used to measure the extrinsic (tissue specific) coagulation cascade pathway.
Prothrombin Time (PT time)
Test used to measure the intrinsic (contact activation) coagulation cascade pathway.
Activated Partial Thromboplastin Time (aPTT time)
What is the International Normalized Ratio?
Different labs use different reagents for PT and aPTT times. So the times can vary from lab to lab for the same person. The INR corrects for differences in the thromboplastin reagents used by different laboratories.
What tests are run to assess the efficacy of warfarin, unfractionated heparin, and for low molecular weight heparin?
Warfarin: PT time
UF heparin: aPTT time
LMWH: Factor Xa inhibition assay
Aspirin (ASA)
Platelet Inhibitor
MOA: irreversibly inhibits COXs to prevent thromboxane A2 formation.
Ind: acute MI, used for lifetime in Coronary Artery Syndrome
AE: GI upset, asthma aggravation (esp w/ nasal polyps), Tinnitus
Contra: ASA allergy, asthma
Ticlopidin
Platelet Inhibitor (Theinopyridine) MOA: inhibits ADP-mediated platelet activation
Ind: secondary prevention after MI, coronary stenting, acute coronary syndrome
AE: bleeding, severe neutropenia, thrombocytopenic purpura
Clopidogrel
Platelet Inhibitor (Theinopyridine) MOA: inhibits ADP-mediated platelet activation
Ind: secondary prevention after MI, coronary stenting, acute coronary syndrome
AE: bleeding
Metabolized by CYP 2C19 and 30% of population don’t have this enzyme functioning well
Prasugrel
Platelet Inhibitor (Theinopyridine) MOA: inhibits ADP-mediated platelet activation
Ind: acute coronary syndrome for which percutaneous coronary intervention is planned
AE: more severe bleeding than clopidogrel
CI: age>75, previous TIA or CVA, weight <60kg
Ticagrelor
Platelet Inhibitor (Non-theinopyridine) MOA: reversibly binds ADP receptors to inhibit platelet activation
Ind: acute coronary syndromes (has less composite endpoints: recurring or serious cardiovascular issues like MI, CVA, CABG surgery)
AE: bleeding but not as severe as theinopyridines
Abciximab
Platelet Inhibitor
MOA: GP IIb-IIIa inhibitor to prevent aggregation
Ind: acute coronary syndrome with anticipation percutaneous coronary intervention
AE: bleeding, thrombocytopenia
Eptifibatide
Platelet Inhibitor
MOA: GP IIb-IIIa inhibitor to prevent aggregation
Ind: acute coronary syndrome with anticipation percutaneous coronary intervention
AE: bleeding, thrombocytopenia
Tirofiban
Platelet Inhibitor
MOA: GP IIb-IIIa inhibitor to prevent aggregation
Ind: acute coronary syndrome with anticipation percutaneous coronary intervention
AE: bleeding, thrombocytopenia
Dipyridamole
Platelet Inhibitor
MOA: increases cAMP to decrease calcium leading to decreased aggregation
Ind: adjunct to other antithrombotic, not very effective alone
Cilostazol
Platelet Inhibitor
MOA: phosphodiesterase inhibitor for vasodilation
Ind: ambulatory claudication (impairmed walking or pain with walking)
Warfarin
Anti-coagulant
MOA: inhibits epoxide reductase (no reduction of Vit. K for coagulation cascade)
Long half-life and should always be dosed with heparin for a few days.
Ind: hypercoagulable states, anticoagulant in atrial fib or artificial valves
AE: bleeding, skin necrosis, Teratogenic
CI: avoid large loading dose due to inhibition of Protein C (natural anticoagulant). Creates paradoxical hypercoagulable state.
avoid in pregnancy
Treatment for excessive bleeding due to warfarin use.
- Stop Warfarin
2. Vit. K supplementation
Unfractionated (UF) Heparin
Anti-coagulant
MOA: Combines with Antithrombin IIIa to inhibit Factor Xa, also inhibits thrombin formation
Ind: anticoagulant, used in atrial fib, artificial heart valves, prevents hypercoagulation with warfarin use
AE: bleeding, osteoporosis, skin necrosis, Heparin-Induced Thrombocytopenia (HIT)
Enoxaparin
Anti-coagulant (LMWH)
MOA: combines with Antithormin IIIa to inhibit Factor Xa
Ind: anticoagulant used in atrial fib, artificial heart valves
AE: bleeding, osteoporosis, skin necrosis, alopecia
CI: renal insufficiency
Dalteparin
Anti-coagulant (LMWH)
MOA: combines with Antithormin IIIa to inhibit Factor Xa
Ind: anticoagulant used in atrial fib, artificial heart valves
AE: bleeding, osteoporosis, skin necrosis, alopecia
CI: renal insufficiency
Tinzaparin
Anti-coagulant (LMWH)
MOA: combines with Antithormin IIIa to inhibit Factor Xa
Ind: anticoagulant used in atrial fib, artificial heart valves
AE: bleeding, osteoporosis, skin necrosis, alopecia
CI: renal insufficiency
Treatment of bleeding due to heparin use.
- Stop Heparin
2. If serious use Protamine Sulfate
What are the two types of Heparin Induced Thrombocytopenia and Tx for each.
- Non-immune mediated: self-limiting, stop heparin
2. Immune-Mediated: stop heparin and a direct thrombin inhibitor
Lepirudin
Anti-coagulant (direct thrombin inhibitor)
MOA: inhibit thrombin activity
Ind: anticoagulant for atrial fib, stent placement, artificial valves, HIT
AE: bleeding
Bivalirudin
Anti-coagulant (direct thrombin inhibitor)
MOA: inhibit thrombin activity
Ind: anticoagulant for atrial fib, stent placement, artificial valves, HIT
AE: bleeding
Argatroban
Anti-coagulant (direct thrombin inhibitor)
MOA: inhibit thrombin activity
Ind: anticoagulant for atrial fib, stent placement, artificial valves, HIT
AE: bleeding
Dabigatran
Anti-coagulant (direct thrombin inhibitor)
MOA: inhibit thrombin activity
Ind: anticoagulant for atrial fib, stent placement, artificial valves, HIT
AE: bleeding, rebound hypercoagulability when suddenly stopped = stroke, pulmonary embolism
Fondaparinux
Anti-coagulant (Factor Xa inhibitor)
MOA: binds antithrombin III to inhibit Factor X activation
Ind: DVT prophylaxis, DVT treatment, pulmonary embolism treatment
AE: bleeding (no antidote)
Rivaroxaban
Anti-coagulant (Factor Xa inhibitor)
MOA: prevents Factor X activation
Ind: DVT prophylaxis, reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
AE: bleeding (no antidote), rebound hypercoagulable state if stopped suddenly (use LMWH)
Apixaban
Anti-coagulant (Factor Xa inhibitor)
MOA: binds antithrombin III to inhibit Factor X activation
Ind: reduce stroke and PE in patients w/ non-valvular atrial fib,
AE: rebound hypercoagulability when stopped suddenly
Which drugs bind antithrombin III to inhibit factor Xa?
- All Heparins
- All drugs with X in the name for factor X
(exception Abciximab)
