Anti-clotting drugs Flashcards
What are the parenteral directing acting factor II inhibitors?
- Argatroban (IV)
- Bivalirudin (IV)
- Desirduin (SubQ)
What are the parenteral direct acting factor Xa inhibitors?
None
What are the parenteral indirect acting (heparin derived inhibitors)? Those that inhibit both factor II and Xa
- UFH (IV, SubQ)
- Bemiparin (LMWH SubQ)
- Enoxaparin (LMWH SubQ)
- Tinzaparin (LMWH SubQ)
What is an example of a parenteral indirect specific factor Xa inhibitor?
Fondaparinux (SubQ)
UFH, LMWH, and fondaparinux all bind to what protein? What does this protein do?
Anti-thrombin, which inactivates thrombin (and factor Xa)
Heparins are administered ___ due to __ size and lack of oral absorption
parenterally (IV/SC, not MI); large
What is a toxicity of UFH?
HIT; leading to activation of platelets and platelet removal by splenic macrophages
What is an alternative to heparins in patients with HIT?
Argatroban
What are the oral direct acting thrombin inhibitors?
Dabigatran
What are the oral direct acting factor Xa inhibitors?
Apixaban, rivaroxaban, edoxaban
What are the indirect acting vitamin K inhibors?
Warfarmin/coumadin
What enzyme in particular is affected via warfarin? What factors are reduced?
Warfarin Inhibits Vitamin K reductase; 2, 7, 9, 10 C and S are affected
What are the half lives for factor IIa, VIIa, IXa, and Xa respectively?
60h, 6h, 24h, 40h. These factors must degrade before effects begin
How long may it take for warfarin to reach therapeutic levels?
1 week. Thus heparin bridging is used
What are some indirect thrombin inhibitor drug interactions? (warfarin)
Warfarin travels in blood stream via albumin. NSAIDs and some other drugs also bind to albumin and can therefore kick off warfarin. This would lead to free warfarin thus increasing risk of bleeding and amplified effects of warfarin
What polymorphisms may ensure with warfarin?
VKORC1 and CYP2C9 polymorphisms affect dosing. Those with these polymorphisms should be given lower doses.
- VKORC1 is part of vitamin K reductase
- CYP2C9 is part of the conversion from S-warfarin to 7-OH warfarin. Increases conversion 4x?
What are some foods that can affect warfarin dosing?
Parsley, swiss chard, Kale, Dandelion greens (All these contain vitamin K in high levels)
What are some birth defects that can arise from warfarin?
Fetal warfairn syndrome (bone defects, intellectual disability etc.). Category X rating
What are some drugs that can increase risk of bleeding?
CYPs 1A1, 1A2, 3A4: Amiodarone, cimetidine
CYP2C9: Amiodarone, cimetidine, SMZ/TMP, fluconazole, metronidazole
These cytochromes promote degradation of warfarin, but are degraded by the drugs listed above. So if you adminster one of these other drugs, you’ll increase risk of bleeding since more warfarin will be in circulation.
Cox 1/2 inhibs (Aspirin, ibuprofen) should be used for what conditions?
Unstable angina, MI, stroke
P2Y12 inhibitors should be used for which conditions (Clopidogrel, prasugrel, ticagrelor, ticlopidine)
MI and stroke
GPIIB/IIIA inhibs hsould be used for which conditions? (Abciximab, eptifibitide, tirofiban)
angioplasty/stent placement
Cox-1/2 inhibitors work by what function?
Inhibit TXA2 synthesis in platelets. TXA2 usually activates other platelets and promotes aggregation
P2Y12 inhibitors work by what function? (Clopidogrel, pasugrel, ticagrelor, ticlopidine)
Inhibits ADP receptor, which is used for platelet activation. Clopidogrel and pasugrel are irreversible non-competitive antagonists ADP
What are some pharmacokinetic issues that are relevant with clopidogrel?
Clopidogrel is ingested as an inactive form but is activated by the CYP2C19. And then esterified into its anticoagulant form. Those with reduced CYP2C19 activity will not received benefit of clopidogrel while those with increased CYP2C19 activity will have increased risk of bleeding
Abciximab inhibits clotting by what mechanism?
It is an antibody that binds to GPIIb/IIIa receptors that prevent aggregation
What are some examples of plasminogen activators?
streptokinase, urokinase, alteplase (t-PA)
Thrombin __ fibrin
produces
Plasminogen __ fibrin
degrades
Alteplase and streptokinase work by what mechanism?
They convert inactive plasminogen into active plasmin
What are some drugs that can be given immediatley to treat PE
Streptokinase or alteplase
What drug can be given immediately to treat stroke?
Alteplase. Only effective in select patients. Significant increase in excellent outcome and reduced disability at 3 months
Fibrinolytics should not be given to whom?
Those for whom clotting is “good”. I.e. those with prior intracranial hemorrhage, ischemic stroke within 3 months, suspected aortic dissection, active bleeding, etc.
