Pharm: PE & Thromboembolism

Question 1

What are the parenteral indirect thrombin/Xa inhibitors drug classes? What drugs are in each class?

Answer 1

Unfractionated heparin Low Molecular weight heparins: enoxaparin, dalteparin, tinzaparin Synthetic pentasccharide: fondaparinux

Question 2

What is the MOA of unfractionated heparin?

Answer 2

Binds to & activates antithrombin III to inhibit factor Xa

Forms a tertiary complex to block generation of new thrombin and inhibit existing thrombin

Question 3

Can you use heparin in pregnant women?

Answer 3

Yes, doesn’t cross placenta

Question 4

What is the antidote for heparin?

Answer 4

Protamine (protein with positive charges)

Question 5

How do you mointor the effects of heparin?

Answer 5

intensive aPTT monitoring

Question 6

What are some important heparin toxicities?

Answer 6

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

Question 7

What are the contraindications for heparin?

Answer 7

Uncontrollable bleeding, thrombocytopenia, use during surgery or procedure involving brain, eye, or spinal cord

Question 8

What is the MOA of low-molecular weight heparins?

Answer 8

Inhibits factor Xa ONLY

Question 9

What advantages do low molecular weight heparins have over unfractionated heparin?

Answer 9

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

Question 10

What are some adverse effects of low molecular weight heparins?

Answer 10

Bleeding

HIT

Severe neurologic injury in spinal puncture or epidural anesthesia (esp. if used with aspirin or clopidogrel)

Question 11

What is the antidote for low molecular weight heparins?

Answer 11

Protamine

Question 12

What is the MOA of fondaparinux?

Answer 12

Selective inhibits factor Xa ONLY

Question 13

What are some adverse reactions of fondaparinux?

Answer 13

Bleeding (esp with advancing age and renal impairment)

Question 14

Is fondaparinux reversible with protamine?

What is an advantage of the drug?

Answer 14

Not reversible with protamine

Does not cause HIT (but can lower platelet counts in HIT patients)

Question 15

What are your parenteral direct thrombin inhibitors?

Answer 15

Bivalirudin

Argatroban

Question 16

What is the MOA of bivalirudin?

Answer 16

Directly blocks thrombin

Question 17

What are some limitations of bivalirudin?

Answer 17

Must be given IV

Espensive

No antidote

Anaphylaxis with repeated use

Question 18

What are some advantages of bivalirudin?

Question 19

What is the MOA of argatroban?

Answer 19

Directly binds the catalytic site of thrombin to reduce development of new thrombosis

Question 20

What are the indications for use of argatroban?

Answer 20

Prophylaxis & Tx of thrombosis in patients with HIT

Question 21

What are some limitations of argatroban?

Answer 21

Given IV

Short 1/2 life (~45 minutes)

Risk for hemorrhage

12% develop hematuria

Question 22

What is your coumarin derivative oral anticoagulant?

Answer 22

Warfarin

Question 23

What is the MOA of warfarin?

Answer 23

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

Question 24

Is warfarin useful in emergencies?

Answer 24

No, it is a slow on, slow off drug due to 1/2 life of clotting factors being several days

Question 25

How do you monitor the effects of warfarin?

Answer 25

INR (normalized prothrombin time ratio) Ideally between 2-3 Monitor more frequent when adding or subtracting drugs

Question 26

What are some important drug interactions/toxicities of warfarin?

Answer 26

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)

Question 27

How can you reverse the effects of warfarin?

Answer 27

Administer vitamin K, give fresh whole blood, plasma, or plasma concentrates

Question 28

Why can warfarin cause a pro-coagulant state?

Answer 28

Inhibits production of protein C 1st since it has a shorter 1/2 life Leads to unchecked clotting factors which increases risk of clot

Question 29

What drugs are in the direct oral anticoagulant (DOAC) factor Xa inhibitor class?

Answer 29

"xabans" Rivaroxiban Apixaban Endoxaban

Question 30

What is the antidote for the DOAC factor Xa inhibitors?

Answer 30

Andexant alfa

Question 31

What is the MOA of rivaroxaban (and apixaban/edoxaban)?

Answer 31

Directly inhibits activated factor X, directly inhibits production of thrombin

Question 32

What are some advantages of rivaroxaban over warfarin?

Answer 32

Rapid onset Fixed dosage Lower bleeding risk Fewer drug interactions No need for INR monitoring

Question 33

What are some toxicities of rivaroxaban?

Answer 33

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

Question 34

What drugs are in the DOAC thrombin inhibitor class?

Answer 34

Dabigatran

Question 35

What is the MOA of dabigatran?

Answer 35

Reversible direct thrombin inhibitor

Question 36

What is the antidote for dabigatran?

Answer 36

idarucizumab

Question 37

What advantages does dabigatran have over warfarin?

Answer 37

Rapid onset No need to monitor Fewer drug/food interaction Lower bleeding risk Same dose used in all patients

Question 38

What are the toxicities associated with dabigatran?

Answer 38

Bleeding Role in HIT?

Question 39

When do you anticoagulate subsegmental PEs?

Answer 39

If there is a high risk of recurrence, otherwise surveillance

Question 40

Should you treat acute PE out of the hospital?

Answer 40

Yes if home care is adequate, otherwise release from hospital after 5 days

Question 41

When should you give systemic thrombolytic therapy for PE?

Answer 41

Give if SBP\<90mmHG and low bleeding risk or if patient deteriorates after starting anticoagulant therapy Don't give if SBP\>90mmHg

Question 42

When should you remove thrombus using catheter as inital tx?

Answer 42

Perfer systemic fibrolytic therapy from peripheral vein but can use catheter if circumstances warrent and resources available

Question 43

Should you do a pulmonary thoromboendarterectomy to tx chronic thromboembolic pulmonary HTN?

Answer 43

Yes, by an experinced team