What is the difference between arterial clots and venous clots?
Arterial = primarily platelets, treat with antiplatelet meds
Venous = primarily fibrin, treat with anticoagulants - inhibit coagulation cascade
What are the 4 major antiplatelet therapies?
Cyclooxygenase inhibitors: aspirin (irreversible), NSAIDS (competitive inhibitors- used more for pain relief)
GP IIb/IIa inhibitors (this complex is important for getting platelets to stick together)
ADP receptor inhibitors - ticlopidine, clopidogrel, prasugrel, ticagrelor
Aspirin mechanism of action
Low doses: blocks thromboxane A2 production --> block platelet aggregation & vasoconstriction
Higher doses: also blocks PGI2 --> blocks prostacyclin production too! Inhibits platelet aggregation & causes vasodilation
Increases cAMP production
Blocks Ca release from dense granules, blocking AA production & decreasing thromboxane A2 production
Enhances aspirin's effect on platelet aggregation
Glycoprotein IIb/IIIa inhibitors mechanism of action
Interfere with fibrinogen-induced platelet aggregation
Fab fragments- abciximab
Peptide-bast antagonists - eptifibatide
Small molecule inhibitors- tirofiban
Potent: platelet count --> 0
Abciximab: 30 min half life
Eptifabatide/tirofaban: 2-2.5 hours
Best for short term bc too potent for long term!
ADP receptor inhibitors- mechanism? use? SE?
Block P2Y-12 receptor which inhibits ADP-induced activation of platelets
Ticlopidine (rarely used-SE), clopidogrel (major agent), prasugrel, ticagrelor
Long half life, no reversing agent
Used for unstable angina, MI, percutaneous coronary intervention, secondary stroke prophylaxis, periph vasc dis
Synergy with aspirin
SE=bleeding, thrombotic thrombocytopenic purpura (TTP- dangerous), neutropenia
What are the anticoagulant?
Factor Xa inhibitors
Direct thrombin inhibitors
What is rivaroxaban?
Oral Factor Xa inhibitor
VTE (venous thromboembolism) prophylaxis, stroke prevention in non-valvular Afib, VTE treatment
What is apixaban?
Treat non-valvular Afib
Problematic in renal dysfunciton bc renally excreted
What are the direct thrombin inhibitors?
Block thrombin, more potent than heparin
Includes: Argatroban (small molecule blocker of thrombin, problematic in liver disease), bivalirudin=angiomax (unstable angina/angioplasty), desirudin (VTE prophylaxis), Dabigatran=Pradaxa (oral direct thrombin inhibitor- lots of press, no DDI/food, bleeding possible-- stroke prevention in nonvalvular AFib)
Inhibits Vitamin K dependent carboxylase activity by preventing reduction of Vitamin K
Doesn't affect proteins already synthesized
Antidote = Vitamin K
What is thrombolytic therapy?
Lysing clots that have already formed
Problem: doesn't discrimiate between therapeutic and pathologic thrombosis --> increased risk of hemorrhage compared with other antithrombotic therapties
Only therapy that prevents tissue death in acute aterial thrombosis (in MI and stroke-- more important in stroke!)
Lyses hemostatic plugs everywhere --> SE= bleeding, esp CNS
What are the 3 classes of thrombolytic therapy?
Streptokinase: binds plasminogen, activates a second plasminogen molecule to plasmin
Urokinase: activates plasminogen directly
TIssue plasminogen activator: activates plasminogen directly