Drugs for Thromboembolic Disorders

Question 1

What makes up red clots vs. white clots?

Answer 1

Red clots - from venous circulation; contains fibrin.

White clots - from arterial circulation; contains platelets.

Question 2

aPTT measures which pathway?

Answer 2

Intrinsic pathway

Question 3

PT measures which pathway?

Answer 3

Extrinsic pathway (INR)

Question 4

Heparin MOA and effects:

When is it given?

PKs:

S/E:

Answer 4

Blocks generation of Thrombin (inhibition of factor Xa) and inactivates Thrombin to prevent formation of *red clots. It is a massive molecule.

Given in urgent scenarios with a rapid onset of SX (PE, stroke, DVT, etc.).
It can be given during pregnancy, as it does not cross the placenta.

Must be given parenterally and binds non-specifically, so it has a short half life (1.5 hrs).

Bleeding, hypersensitivity reactions (Heparin-induced thrombocytopenia), signifiant problems in the CNS.

Question 5

Enoxaparin MOA and effects:

When is it given?

PKs:

S/E:

Answer 5

Blocks factor Xa and inhibits Thrombin formation. Much smaller molecule.

DVT or post-orthopedic surgeries.

Easier to use (first choice now) and has a longer half-life of 4-6 hrs. More expensive.

Bleeding, Heparin-induced thrombocytopenia, significant problems in the CNS.

Question 6

Fondaparinux MOA and effects:

When is it given?

PKs:

S/E:

Answer 6

Blocks factor Xa and prevents Thrombin formation. Slightly more effective than enoxaparin, but greater risk of bleeding.

Preventing DVT, treating acute PE or DVT w/ Warfarin.

Predictable PKs w/ subQ daily dose.

Bleeding, but does NOT cause Heparin-induced thrombocytopenia.

Question 7

Argatroban MOA and effects:

When is it given?

PKs:

S/E:

Answer 7

Directly binds catalytic site of Thrombin and inhibits it.

Prophylactic treatment, and given to patients with Heparin-induced thrombocytopenia.

Given in IV, short half-life.

Hemorrhage, bleeding.

Question 8

Warfarin MOA and effects:

When is it given?

PKs:

S/E:

Answer 8

Antagonizes Vit. K and does not allow for clot formation (decreases amount of factors II, VII, IX, X, and protein C and S).

Prophylaxis. Not used in urgent scenarios, as it takes some time for effects to start (protein C and S have less half-life, so they have to be metabolized).

Given orally. Slow onset, offset. Must monitor INR.

Bleeding and cutaneous necrosis. Can cross the placenta.

Question 9

What is the target range for INR?

Answer 9

2.0-2.5

Question 10

Rivaroxaban MOA and effects:

When is it given?

PKs:

S/E:

Answer 10

Direct inhibitor of activated factor X and inhibits production of Thrombin.

Prevention of DVT/PE. Prevention of stroke in AFib.

Oral.

Bleeding, hepatic/renal effects, unsafe in pregnancy, interacts w/ CYP3A4.

Question 11

What are some advantages of Rivaroxaban to Warfarin?

Answer 11

Rapid onset
Fixed dose
Less bleeding
Less interactions
No need to monitor INR

Question 12

Dabigatran MOA and effects:

When is it given?

PKs:

S/E:

Answer 12

Reversible direct Thrombin inhibitor. Rapid onset, no need to monitor.

Prevent stroke, embolism in AFib. Contraindicated in pts. w/ mechanical heart.

Pills are unstable and require separate housing.

Bleeding.

Question 13

Antidote for Warfarin

Answer 13

Vit K, prothrombin complex concentrate

Question 14

Antidote for Rivaroxaban

Answer 14

Andexanet alfa

Question 15

Antidote for Dabigatron

Answer 15

Idarucizumab

Question 16

What does Aspirin block?

Answer 16

COX-1 and decreases TXA2 production and persists for life of platelet

Question 17

Clopidogrel MOA and effects:

When is it given?

PKs (unique aspect):

S/E:

Answer 17

Irreversible blockade of P2Y12 receptors on platelets and inhibits platelet aggregation. Persists for lifetime of platelet.

Prevent stenosis of coronary stents. Secondary prevention of MI and stroke.

It is a pro-drug**, not good for patients with liver dz.

Generally well-tolerated.

Question 18

Dipyridamole MOA and effects:

When is it given?

Answer 18

Uncertain, but somehow suppresses platelet aggregation.

Given w/ Aspirin to prevent TIA.

Question 19

Cilostazol MOA and effects:

When is it given?

Answer 19

Phosphodiesterase inhibitor (prolongs life of cAMP in cells and platelets). Inhibits aggregation and is a vasodilator.

Claudication

Question 20

Abciximab MOA and effects:

When is it given?

Answer 20

Fab fragment of a monoclonal Ab that inhibits GpIIb/IIIa receptors and prevents fibrinogen binding. Inhibits aggregation of platelets.
Most effective anti-platelets drug.

Acute coronary syndromes, percutaneous coronary intervention.

Question 21

Alteplase (t-PA) MOA and effects:

When is it given?

PKs:

S/E:

Answer 21

Catalyzes conversion of clot-bound plasminogen to plasmin (clot buster)

Acute MI, acute ischemic stroke, acute massive PE.

Large molecule and must be given parentally. Short half-life.

Bleeding, IC hemorrhage. Destroys pre-existing clots.

Question 22

Antidote for (Alteplase) t-PA

Answer 22

Aminocaproid acid

Question 23

Urokinase (uPA) MOA and effects:

When is it given?

PKs:

S/E:

Answer 23

Activates fibrinolysis (activates plasminogen)

PE.

Injected IV slowly

Potentially fatal hemorrhage