Drugs For Thromboembolic Disorders (Konorev) Flashcards
What pathologic conditions are associated with white thrombi?
Local ischemia d/t arterial occlusion (in coronary arteries: MI/unstable angina)
This type of thrombus forms in low-prssure veins and in the heart; result of platelet bidning and aggregation followed by formation of bulky fibrin tails in which RBCs become enmeshed.
Red thrombus (fibrin-rich with trapped RBCs)
What are pathologic conditions associated with red thrombi?
Pain and severe swelling, embolism and distal pathology (embolic stroke)
This type of drug regulates the function and synthesis of clotting factors and is primarily used to prevent clots from forming in the venous system and heart (RED THROMBI)
Anticoagulants
This type of drug inhibits platelet function and is primarily used to prevent clots from forming in the arteries (white thrombi)
Antiplatelet drugs
This type of drug destroys blood clots after they are formed. These re-establish blood flow through vessels once clots have formed
Thrombolytic
Heparin sodium is this type of anticoagulant
Parenteral –> Indirect thrombin and FXa inhibitor –> HMW or UFH
Enoxaprin, Tinzaparin, and Dalteparin are this type of anticoagulant:
Parenteral –> Indirect thrombin and FXa inhibitor –> LMW
Fondaparinux is this type of anticoagulant:
Parenteral –> Indirect thrombin and FXa inhibitor –> Synthetic pentasaccharide
Lepirudin, Bivalirudin, and Argatroban are this type of anticoagulant:
Parenteral –> Direct thrombin inhibitors
What is the MOA of indirect thrombin and FXa inhibitors?
Bind plasma serine protease inhibitor ANTITHROMBIN III
Antithrombin III inhibits several clotting factor proteases, esp Thrombin (IIa), IXa, and Xa. Heparin increases antithrombin III activity 1000fold
This anticoagulant inhibits the activity of both thrombin and FXa
HMW heparin
This anticoagulant inhibits FXa with little effect on thrombin
LMW heparin
This anticoagulant inhibits FXa activity with no effect on thrombin
Fondaparinux
What is the MOA of DIRECT thrombin inhibitors (Parenteral)?
Direct inhibition of the protease activity of thrombin
The MOA of these anticoagulants is bivalent direct thrombin inhibitors (bind at both active site and substrate recognition site)
Lepirudin and Bivalirudin
The MOA of this anticoagulant is an inhibitor binding only at the thrombin active site
Argatroban
Warfarin (coumadin) is this type of anticoagulant:
Oral –> Coumarin anticoagulant
Rivaroxaban, Apixaban, Edoxaban are these types of anticoagulant:
Oral –> Novel oral anticoagulants (NOAC) –> Factor Xa inhibitors
Dabigatran is this type of anticoagulant:
Oral –> NOAC –> Direct thrombin inhibitor
What is the MOA of warfarin?
Inhibits reactivation of Vit K by inhibiting Vit K epoxide reductase. Inhibits carboxylation of GGCX in prothrombin and factors VII,IX, and X, making them inactive
What makes warfarin dosing so difficult?
Narrow therapeutic window of the drug and high individual variability, i.e., genetics, disease states, drug-drug interactions, diet
What is the INR for pts on warfarin?
2.0-3.0
Rivaroxaban, Apixaban, and Edoxaban inhibit ___
Xa
Dabigatran inhibits ___
IIa (thrombin)
Who gets parenteral anticoagulants?
Pts with DVT, atrial arrhythmias and other conditions that predispose towards RED THROMBI
Tx/prevention of embolic stroke, PE
Prevent emboli during surgery or in hospitalized pts
Heparin locks
Who gets oral anticoagulants?
Used to prevent thrombosis or prevent/treat thromboembolism
A Fib
Prosthetic heart valves
What is the antidote for HMW and LMW heparin?
Protamine sulfate
What is the antidote for warfarin?
Vit K, prothrombin complex concentrate
What is the antidote for NOAC-DTI?
Idarucizumab
Which coagulation test is specific for heparin?
PTT, anti-Xa –> the intrinsic pathway
Which coagulation test is specific for warfarin?
PT-based (INR) –> Extrinsic pathway
What blood coagulation test is specific for NOAC-FXa inhibitors?
Anti-Xa
What blood coagulation test is specific for NOAC-DTI?
Diluted thrombin time (TT)
What type of antiplatelet drug is aspirin?
Inhibitor of TxAs synthesis
What type of antiplatelet drug is Clopidogrel, Prasugrel, Ticlopidine, and Ticagrelor?
ADP receptor blocker
What type of antiplatelet drug is Abciximab, Eptifibatide, and Tirofiban?
Platelet glycoprotein receptor blocker
What type of antiplatelet drug is Dipyridamole and Cilostazol?
Phosphodiesterase inhibitor
What is the MOA of aspirin?
Inhibit COX
Decreased TxA2 production
What is the MOA of ADP receptor blockers?
Inhibition of AC by ai is relieved
Increased production of cAMP
Clopidogrel, ticlopidine, and prasugrel
What is the MOA of phosphodiesterase inhibitors?
Inhibit cAMP degradation
Levels of cAMP in platelets are increased
Dipyramidole and cilostazol
Platelet GP receptor antagonists target this sequence to prevent binding of ligands to the GP IIb/IIIa receptor to inhibit platelet aggregation
RGD
Abciximab, Tirofiban, Eptifibatide
What are clinical uses of antiplatelet drugs?
Prevent thrombosis in unstable angina and other acute coronary syndromes
Prevent ischemic stroke and arterial thrombosis in peripheral vascular disease
Pts undergoing percutaneous coronary angioplasty and stunting
This combo can be used to prevent cerebrovascular ischemia:
Dipyridamole (PDE inhibitor) with aspirin
This combo can be used to tx pts with prosthetic heart valves
Dipyridamole (PDE inhibitor) with warfarin
This drug can be used to tx intermittent claudication
Cilostazol
What is the MOA of thrombolytic drugs?
Activate endogenous fibrinolytic system by converting plasminogen into plasmin
Alteplase, Reteplase, and Tenecteplase are these types of thrombolytics:
tPA drugs
Urokinase is this type of thrombolytic drug:
uPA activator
Streptokinase is this type of thrombolytic drug:
Streptokinase preparation purified from bacteria
What are clinical uses of thrombolytic drugs?
Acute embolic/thrombotic stroke (within 3 hr) Acute MI (within 3-6 hr) PE DVT Ascending thrombophlebitis
This type of thrombus forms in high-pressure arteries and is the result of platelet binding to the damaged endothelium and aggregation with little involvement of fibrin.
White (platelet-rich) thrombus
