Pharm: PE & Thromboembolism Flashcards
What are the parenteral indirect thrombin/Xa inhibitors drug classes? What drugs are in each class?
Unfractionated heparin Low Molecular weight heparins: enoxaparin, dalteparin, tinzaparin Synthetic pentasccharide: fondaparinux
What is the MOA of unfractionated heparin?
Binds to & activates antithrombin III to inhibit factor Xa
Forms a tertiary complex to block generation of new thrombin and inhibit existing thrombin
Can you use heparin in pregnant women?
Yes, doesn’t cross placenta
What is the antidote for heparin?
Protamine (protein with positive charges)
How do you mointor the effects of heparin?
intensive aPTT monitoring
What are some important heparin toxicities?
Bleeding: use extreme caution in pts with bleeding tendancies/disorders, monitor skin, BP, HR, urine, and stools
In severe cases, can cause spinal or epidural hematoma which can cause paralysis (ask about back/pelvic pain)
Heparin Induced Thrombocytopenia - reduced platelet counts and increased thromboembolic events
What are the contraindications for heparin?
Uncontrollable bleeding, thrombocytopenia, use during surgery or procedure involving brain, eye, or spinal cord
What is the MOA of low-molecular weight heparins?
Inhibits factor Xa ONLY
What advantages do low molecular weight heparins have over unfractionated heparin?
Easier to use bc dosing is predictable and can be used at home without regular monitoring
Longer 1/2 lives (~6hrs)
Now first choice for tx and prevention of DVT
What are some adverse effects of low molecular weight heparins?
Bleeding
HIT
Severe neurologic injury in spinal puncture or epidural anesthesia (esp. if used with aspirin or clopidogrel)
What is the antidote for low molecular weight heparins?
Protamine
What is the MOA of fondaparinux?
Selective inhibits factor Xa ONLY
What are some adverse reactions of fondaparinux?
Bleeding (esp with advancing age and renal impairment)
Is fondaparinux reversible with protamine?
What is an advantage of the drug?
Not reversible with protamine
Does not cause HIT (but can lower platelet counts in HIT patients)
What are your parenteral direct thrombin inhibitors?
Bivalirudin
Argatroban
What is the MOA of bivalirudin?
Directly blocks thrombin
What are some limitations of bivalirudin?
Must be given IV
Espensive
No antidote
Anaphylaxis with repeated use
What are some advantages of bivalirudin?
What is the MOA of argatroban?
Directly binds the catalytic site of thrombin to reduce development of new thrombosis
What are the indications for use of argatroban?
Prophylaxis & Tx of thrombosis in patients with HIT
What are some limitations of argatroban?
Given IV
Short 1/2 life (~45 minutes)
Risk for hemorrhage
12% develop hematuria
What is your coumarin derivative oral anticoagulant?
Warfarin
What is the MOA of warfarin?
vitamin K antagonist, inhibits vitamin K epoxide reductase 1 to prevent vitamin K activation
decreases production of clotting factors II, VII, IX & X as well as protein C and protein S
Is warfarin useful in emergencies?
No, it is a slow on, slow off drug due to 1/2 life of clotting factors being several days
How do you monitor the effects of warfarin?
INR (normalized prothrombin time ratio)
Ideally between 2-3
Monitor more frequent when adding or subtracting drugs
What are some important drug interactions/toxicities of warfarin?
Bleeding
Pregnancy category X (crosses placenta and causes hemorrhage, death)
Interacts with drugs that promote bleeding
Many interactions with drugs that increase/decrease effects (oral contraceptives, vitamin K, acetaminophen, Bactrum)
How can you reverse the effects of warfarin?
Administer vitamin K, give fresh whole blood, plasma, or plasma concentrates
Why can warfarin cause a pro-coagulant state?
Inhibits production of protein C 1st since it has a shorter 1/2 life
Leads to unchecked clotting factors which increases risk of clot
What drugs are in the direct oral anticoagulant (DOAC) factor Xa inhibitor class?
“xabans”
Rivaroxiban
Apixaban
Endoxaban
What is the antidote for the DOAC factor Xa inhibitors?
Andexant alfa
What is the MOA of rivaroxaban (and apixaban/edoxaban)?
Directly inhibits activated factor X, directly inhibits production of thrombin
What are some advantages of rivaroxaban over warfarin?
Rapid onset
Fixed dosage
Lower bleeding risk
Fewer drug interactions
No need for INR monitoring
What are some toxicities of rivaroxaban?
Bleeding (epidural hematoma, intracranial, GI, adrenal bleeding)
Avoid in pts with renal or hepatic impairment
Unsafe in pregnancy
Don’t combine with other anticoagulants
Interactions with CYP3A4
What drugs are in the DOAC thrombin inhibitor class?
Dabigatran
What is the MOA of dabigatran?
Reversible direct thrombin inhibitor
What is the antidote for dabigatran?
idarucizumab
What advantages does dabigatran have over warfarin?
Rapid onset
No need to monitor
Fewer drug/food interaction
Lower bleeding risk
Same dose used in all patients
What are the toxicities associated with dabigatran?
Bleeding
Role in HIT?
When do you anticoagulate subsegmental PEs?
If there is a high risk of recurrence, otherwise surveillance
Should you treat acute PE out of the hospital?
Yes if home care is adequate, otherwise release from hospital after 5 days
When should you give systemic thrombolytic therapy for PE?
Give if SBP<90mmHG and low bleeding risk or if patient deteriorates after starting anticoagulant therapy
Don’t give if SBP>90mmHg
When should you remove thrombus using catheter as inital tx?
Perfer systemic fibrolytic therapy from peripheral vein but can use catheter if circumstances warrent and resources available
Should you do a pulmonary thoromboendarterectomy to tx chronic thromboembolic pulmonary HTN?
Yes, by an experinced team
