Drugs for Thromboembolic Disorders Flashcards
What makes up red clots vs. white clots?
Red clots - from venous circulation; contains fibrin.
White clots - from arterial circulation; contains platelets.
aPTT measures which pathway?
Intrinsic pathway
PT measures which pathway?
Extrinsic pathway (INR)
Heparin MOA and effects:
When is it given?
PKs:
S/E:
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.
Enoxaparin MOA and effects:
When is it given?
PKs:
S/E:
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.
Fondaparinux MOA and effects:
When is it given?
PKs:
S/E:
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.
Argatroban MOA and effects:
When is it given?
PKs:
S/E:
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.
Warfarin MOA and effects:
When is it given?
PKs:
S/E:
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.
What is the target range for INR?
2.0-2.5
Rivaroxaban MOA and effects:
When is it given?
PKs:
S/E:
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.
What are some advantages of Rivaroxaban to Warfarin?
Rapid onset Fixed dose Less bleeding Less interactions No need to monitor INR
Dabigatran MOA and effects:
When is it given?
PKs:
S/E:
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.
Antidote for Warfarin
Vit K, prothrombin complex concentrate
Antidote for Rivaroxaban
Andexanet alfa
Antidote for Dabigatron
Idarucizumab
What does Aspirin block?
COX-1 and decreases TXA2 production and persists for life of platelet
Clopidogrel MOA and effects:
When is it given?
PKs (unique aspect):
S/E:
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.
Dipyridamole MOA and effects:
When is it given?
Uncertain, but somehow suppresses platelet aggregation.
Given w/ Aspirin to prevent TIA.
Cilostazol MOA and effects:
When is it given?
Phosphodiesterase inhibitor (prolongs life of cAMP in cells and platelets). Inhibits aggregation and is a vasodilator.
Claudication
Abciximab MOA and effects:
When is it given?
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.
Alteplase (t-PA) MOA and effects:
When is it given?
PKs:
S/E:
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.
Antidote for (Alteplase) t-PA
Aminocaproid acid
Urokinase (uPA) MOA and effects:
When is it given?
PKs:
S/E:
Activates fibrinolysis (activates plasminogen)
PE.
Injected IV slowly
Potentially fatal hemorrhage
