Hematologic Agents Flashcards
Define thrombosis and describe differences between venous and arterial thrombosis
It is the inappropriate clot formation
Arterial: Ruptured atherosclerotic plaques, revealing Platelet rich center (White Thrombus)
Venous: Platelet poor plugs (Red thrombus), occur at valve plugs where there is stasis, DVT
What are common causes of thrombosis?
Heriditary factors: antithrombin def, Prot C def, Prot S def, Factor V, Prothrombin gene mutation
Acquired factors: Age, Previous VTE, Cancer, Obesity
Triggering factors: sx, immobilization, pregnancy, estrogen, plaque rupture, mechanical heart valve
MOA: Argatroban Lepirudin Bivalirudin Dabigatran
Direct thrombin Inhibitors
all are parenteral administration except Dabigatran, which is oral
MOA: Fondaparinux
Indirect inhibitor of thrombin/factor Xa
its the synthetic analog of pentasaccharide sequence of heparin
MOA: Heparin
Indirect inhibitor of thrombin via antithrombin
binds AT and increases affinity for factor Xa and also for Thrombin
MOA: Vorapaxar
*****
PAR antagonst. Prevents thrombotic events in pnts with a hx of MI
MOA:
Rivaroxaban
Apixaban
Direct factor Xa inhibitors
MOA: Warfarin
Vitamin K antagonist. competes for Vit K receptor
MOA: Enoxaparin (Low molecular weight Heparin)
Indirect inhibitor of factor Xa
MOA:
Abciximab
Eptifibatide
Tirofiban
Glycoprotein IIb/IIIa antagonists
Abciximab: antigen binding segment of Monoclonal AB
Eptifibatide: Peptide that binds
Tirofiban: Small molecule that binds
All prevent platelet aggregation by preventing fibrinogen cross bridges from forming
MOA: Vorapaxar
Protease Activated Receptor (PAR) antagonist
Compare and contrast the metabolism of P2Y12 antagonists. Clopidogrel Prasugrel Ticagrelor Cangrelor *****
Clopidogrel and prasugrel are irreversible P2Y12 inhibitors that have prodrugs that must be activated by livver.
Ticagrelorr and Cangrelor are reversible inhibitors and do not need to be metabolized. more rapid
Describe warfarin... Pharmacokinetics adverse effects MOA: Route of administration
Pharmacokinetics: close to 100% bioavailability. highly bound to albumin - :takes 3-5 days for effects,
Adverse Effects: Hemorrhage, Placental transfer (NEVER USE DURING PREG), Necrosis
MOA: competes with Vitamin K for binding to Vit K Red
Route of Administration: Oral
What drugs can disrupt the anticoagulation effect of warfarin?
How do they do it?
Vitamin K - competes with warfarin
Fresh plasma
MOA:
Alteplase
Reteplase
Tenecteplase
Tissue PLasminogen activator
acute MI with ST elevation within 12 hours of onset
MOA: Streptokinase
thrombolytic drug. activates plasminogen into plasmin. for emergency MI or PE
MOA:
Aminocaproic acid
Tranexaminic acid
block interaction of plasmin with fibrin
Inhibits fibrinolysis
MOA: Protamine
Inhibits heparin
MOA: Vitamin K
competes with warfarin for vitamin K reductase
MOA: Idarucizumab
Binds to dabigatrin and completely inactivates
What is the general use of Anticoagulants?
keeps coagulation system in check
What is the general use of antiplatelets?
to reduce clotting
What is the general use of fibrinolytics?
to break up clots that are already there
What are the contraindications of using Fibrinolytics?
if it is a NSTEMI, pnt is over 75 >24 hours since onset Stroke in past year bleeding Significant trauma to head in past 3 mo pregnant
Heparin Pharmacokinetics AE MOA ROA
Pharmacokinetics: cleared by Kidney/Liver and also taken up by endothelial cells. CL decreases as dose increases, which inc half life
AE: bleeding, osteoporosis
MOA: binds AT and brings factor Xa and thrombin into contact.
ROA: parenterally
Mechanism of HIT
Heparin binds to Platelet factor 4, antibodies are made agains that, macrophages eat
Enoxaparin Pharmacokinetics AE MOA Contraindications antidotes
Pharmacokinetics: safer, easier, but similar
AE: Protamine only partially reverses
MOA: binds AT and brings in factor Xa
Contraindications: Renal failure
antidotes: Protamine only partially reverses
Fondaparinux Pharmacokinetics AE MOA Contraindications antidotes
Pharmacokinetics: main clearance is by the kidney
AE: only for establishe TE, only does factor Xa
MOA: Binds to AT and causes AT to go after Xa
Contraindications: Renal failure
antidotes: Protamine doesnt work
Direct Thrombin Inhibitors
Pharmacokinetics
MOA
Contraindications
Pharmacokinetics: Only one that can inhibit thrombin AFTER it is bound to fibrin
MOA: binds to thrombin on fibrin
Contraindications: Does not cause HIT
Factor Xa inhibitors Pharmacokinetics MOA Contraindications antidotes
Pharmacokinetics: Oral,
MOA:, Thrombin inhibitor. prevent stroke in a fib pnts. prevent dvt pe
Contraindications: mechanical heart valve
antidotes: Idarucizumab
Route of administration
DTI’s
Factor Xa inhibitors
Factor Xa: Oral
DTI: all are Parenteral except Dabigatran, which is oral
Assays for Warfarin Heparin Dabigitran Fibrinolytics
Warfarin: PT
Heparin: PTT
Dabigitran: Factor Xa assay
Fibrinolytics: ?
Uses for fibrinolytics
Break down a clot alerady there
