Anticoagulants/ antiplatelets Flashcards
Arterial clots
platelet rich
Venous clots
rich in fibrin
Heparin (unfractionated)
complexes and activates antithrombin to increase speed 1000x faster to inactive IIa and Xa; also directly inactivates factor IIa
Heparin problem
zero order elimination (frequent APTT testing), hemorrhage (treated with protamine sulfate) and heparin-induced thrombocytopenia (type 2 = generate antibody against heparin-platelet Factor 4, resulting immune complex activates platelets (use argatroban, a thrombin inhibitor)
Argatroban
directly inhibit thrombin
Low molecular weight heparin (fractionizated)
will not bind to thrombin unlike unfractionated heparin, lower risk of developing type 2 thrombocytopenia, undergoes 1st order elimination (no frequent monitoring)
Warfarin
inhibits vitamin K epoxide reductase to inhibit production of clotting factors 2, 7, 9 ,10 by the liver; delay time to act, 8-10 hours (in blood already)
Warfarin potential problems
crosses placenta (teratogenic), hemorrhage (treat with vitamin K), interaction with other drugs, Cyp2C9, variability in pharmacodynamics and pharmacokinetics
Aspirin
inhibits platelet cyclooxygenase 1 and 2 (thus thromboxane A2); at low does daily aspirin decreases risk of myocardial infarction and ischemic stroke but increase risk of hemorrhagic stroke; increased bleeding time
Clopidogrel (given orally)
developed for people who can not tolerate aspirin; a prodrug for which the active metabolite covalently binds to and inactivates the ADP receptor, thereby inhibits the expression of the GP 2b/3a on the platelet surface; affected by Cyp2C19 variant
Vorapaxar
binds to PAR1 and prevents its activation by thrombin
Dipyridamole
elevates cAMP by inhibiting platelet phosphodiesterase (high cAMP lowers free calcium -> inhibits platelet activation and granule release), and by increasing prostacyclin release from endothelial cells (dilate vessels); used in patients with synthetic material implanted, used in combination with warfarin and heparin
Tirofiban (i.v.)
only used in hospital setting during angioplasty or stenting; binds to the GP 2b/3a receptor, blocking cross-linking of platelets/aggregation
Streptokinase
i.v.; bind to plasminogen, the resulting complex causes activation of other plasminogen molecules to plasmin
Alteplase (tPA)
i.v.; binds directly and catalyzes conversion from plasminogen to plasmin
Aminocaproic acid (antidote)
treats hyperfibrinolysis; binds to plasminogen, blocks activation of plasminogen and the interaction of plasmin with fibrin and fibrinogen
Heparin reversal agent (antidote)
protamine sulfate
Warfarin reversal agent (antidote)
Vitamin K, fresh frozen plasma
Anticoagulants have anti platelet activity
Thrombin -> PAR1 -> txA2 and hemostasis/ thrombosis
