Hematological agents II Flashcards
What is type I heparin induced thrombocytopenia? What is the consequence of this?
Heparin can increase platelet aggregation which causes a decrease in circulation platelet numbers
Little clinical consequence
What is type II heparine induced thrombocytopenia?
Heparine can bind platelet factor 4, which some pts develop antibodies against. This causes thrombosis
Which type of heparin causes HIT: fractionated or unfractionated?
unfractionated
Which are more common in HIT: venous or arterial thromboses?
Venous
Who are more affected by HIT: men or women?
Women
How long does it take platelet counts to fall following heparin administration?
5-10 days
What is enoxaparin?
Lower molecular weight heparin
What is low molecular weight heparin called?
Enoxaparin
What is the major disadvantage to low molecular weight heparin? (2)
Cannot deactiveate thrombin
Protamine only partially reverses it
What are the advantages to low molecular weight heparin? (2)
Easier to dose
Lower risk for HIT
What disease contraindicates low molecular weight heparin?
Renal insufficiency
What is fondaparinux?
Synthetic analog of AT binding pentasaccharide sequence
What is the MOA of fondaparinux?
Binds to antithrombin and increases rate of factor X inhibition
True or false: protamine is only partially effectie against fondaparinux
False–not at all effective
What is the major contraidication with fondaparinux?
Renal disease
What is the monitoring assay for fondaparinux?
anti-factor Xa assay
True or false: monitoring of fondaparinux and LMWH is not as intensive as monitoring regular heparin
True
What is the MOA of hirudin?
Direct thrombin inhibitor at both active sites
Do direct thrombin inhibitors inhibit factor 10?
no
How do you administer hirudin?
parenterally
What is the MOA of lepirudin?
Direct thrombin inhibitor at both active sites
How do direct thrombin inhibitors work?
Directly binding to the active site in thrombin that cleaves fibrinogen into fibrin
What is the MOA of argatroban?
Direct thrombin inhibitor at the active site
What is the MOA of dabigitran?
Direct thrombin inhibitor at the active site
Which direct thrombin inhibitor is given orally?
Dabigitran
What is the major advantage of DTIs vs heparin?
can inhibit thrombin bound to fibrin
What type of drug should you use instead of heparin in cases of HIT?
Direct thrombin inhibitor
What is the MOA of bivalirudin?
Inhibits thrombin by binding directly to active site (direct thrombin inhibitor)
What is the drug used to reverse direct thrombin inhibitors
There is none
What is the MOA of warfarin?
Competes with Vit K for Vit K reductase
What are the factors that need vitamin K?
10 9 7 and 2 (and protein C and S)
What does vitamin K reductase do?
Reduces the oxidized form of Vit K, that is used in factor activation
How long does it take for warfarin to take full effect? Why?
3-5 days
Only affects new factors
What is the enzyme that degrades warfarin? What is the significance of this?
CYP2C9
pts with polymorphisms need lower dose
Why does warfarin have such a high Vd?
Plasma protein bound
What is the test to monitor warfarin?
PT
What are the general steps of performing a PT?
- blood collected in Ca free tube
- thromboplastin added
- Ca added
- time
Generally, what types of drugs are contraindicated with warfarin?
Any drug that interferes with Vit K absorption
Where does Vit K come from? What drugs, then, have to be carefully used when a pt is on warfarin?
Gut bacteria
Abx
Potentiate or reduce the anticoagulant effect of warfarin: NSAIDs. Why?
Potentiate
Interfere with primary hemostasis
Potentiate or reduce the anticoagulant effect of warfarin: SSRIs
Potentiate
Potentiate or reduce the anticoagulant effect of warfarin: anti-platelet drugs
Potentiate
Potentiate or reduce the anticoagulant effect of warfarin: drugs that decrease hepatic metabolism
potentiate
Potentiate or reduce the anticoagulant effect of warfarin: statins . Why?
Potentiate
Use same CYP enzyme, and saturate it
Potentiate or reduce the anticoagulant effect of warfarin: rifampin. Why?
Reduce
Potentiate or reduce the anticoagulant effect of warfarin: carbamazepine. Why?
reduce
Increase hepatic elimination of the drug
Potentiate or reduce the anticoagulant effect of warfarin: renal insufficiency. Why?
Potentiate since hypoalbuemia
Potentiate or reduce the anticoagulant effect of warfarin: decreased hepatic function
Reduce
What is the severe adverse side effect of warfarin use? What causes this?
Necrosis
Precipitous fall in vitamin C
What is the therapeutic INR range for warfarin?
2-3
What are the two things to administer a pt with too high of an INR d/t warfarin use?
Vit K
Administer fresh plasma
What is the MOA of rivaroxaban?
Direct inhibitor of factor X
What is the MOA of apixaban?
Directly inhibits factor X
What are the benefits of the newer oral anticoagulants like rivaroxaban, apixaban, and dabigatran?
- Faster onset
- Low food/drug interactions
- Predictable effect
IS warfarin or heparin safe to take during pregnancy?
Warfarin, no
Heparin, yes
What is the main protein involved in the fibrinolytic system? What activates it?
Plasmin
tPA
Why isn’t there much activation of plasminogen in the plasma if there’s tPA?
Both have higher affinity when bound to fibrin
What is the inhibitor in the plasma that will inhiit plasmi?
Alpha2 plasma inhibitor
How, generally, do the fibrinolytic drugs work?
Activate plasmin from plasminogen
What is the MOA of steptokinase?
forms a complex with plasminogen
What is the MOA of urokinase?
Natrual activator of plasmin, produced by the kidney
What are the two tPA agents used in clinic?
Alteplase
Reteplase
What are the adverse effects of streptokinase?
anaphylaxis
When are fibrinolytic drugs used?
STEMI or new LBBB
Should you use thrombolytics in NSTEMIs?
No
What is the MOA of aminocaproic acid?
Blocks interaction of plasmin with fibrin, thus preventing fibrin degradation
What is the MOA of tranexamic acid?
Blocks interaction of plasmin with fibrin, thus preventing fibrin degradation
What are aminocaproic acid and tranexamic acid used for?
Hemophila treatment
