Pharm-antithromb Flashcards
MOA of aspirin
Irreversibly acetylates a serine residue on COX thus reducing the synthesis of TXA2
MOA of ADP receptor blockers
Bind to ADP receptor P2Y12 thus preventing ADP-mediated increase in COX and Glycoproteins IIb/IIIa
Irreversible ADP receptor blockers
Clopidogrel
Prasugrel
*oral prodrugs with prolonged effect
Clopidogrel is activated by ___ and prasugrel is metabolized by ___
- CYP2C19
2. CYP3A4 and CYP2B6
Reversible ADP receptor blockers
Ticagrelor (oral)
Cangrelor (IV)
Ticagrelor (is/is not) a prodrug and is metabolized by ___. It has a ___ onset of action and it’s half life is ___ hours. It is eliminated by the ___.
Is not CYP3A4 Rapid 8-12 Liver
Cangrelor is metabolized by ___. It has a ___ onset of action and it’s half life is ___ hours. It is eliminated by the ___.
Dephosphorylation
Rapid
3-6
Urine and feces
PAR1 antagonists Route MOA Metabolism Elimination Half life
- Vorapaxar (oral)
- Binds to PAR1 thus blocking thrombin-induced activation of COX1 and GPIIb/IIIa
- Metabolized by CYP3A4
- eliminated by feces
- 159-311 hours
Irreversible GPIIb/IIIa inhibitors
Abciximab - a monoclonal antibody
Reversible GPIIb/IIIa inhibitors
Eptifibitide - synthetic peptide inhibitor
Tirofiban - synthetic nonpeptide inhibitor
MOA of GPIIb/IIIa inhibitors
Bind to GPIIb/IIIa complex and block binding of fibrinogen to GPIIb/IIIa thus inhibiting the final common pathway
Antiplatelet list
- COX inhibitors
- ADP receptor blockers
- GPIIb/IIIa inhibitors
- PAR1 antagonists
Anticoagulant list
- Heparin/like agents
- Xa inhibitors (indirect thrombin inhibitor)
- Thrombin inhibitors (oral direct, IV direct)
- Thrombin synthesis inhibitors
Aspirin clinical uses
- prevention of arterial thrombosis
- acute coronary syndrome
- long term prevention of arterial thrombosis after PCI
- prevent TIA and ischemic stroke
Clopidogrel uses
Alternative for aspirin
*combo of the two for pts undergoing PCI
Prasugrel uses
Prevent PCI-related thrombosis in pts with poor response to clopidogrel
Ticagrelor uses
Usually combined with aspirin for same uses as aspirin because it has a rapid onset of action and is reversible
Vorapaxar uses
Added to aspirin or clopidogrel to provide secondary prevention of thrombotic CV events (stroke, MI), and need for coronary revascularization
GPIIb/IIIa inhibitors uses
Prevent acute arterial thrombosis (PCI-induced) and to treat acute coronary syndrome
Dipyridamole and cilostazol
MOA
Inhibit platelet function by reducing adenosine uptake and cGMP phosphodiesterase activity
Dipyridamole uses
- Combo with aspirin to prevent cerebrovascular ischemia
- combo with warfarin to prevent thromboemboli in pts with artificial heart valves
Cilostazol uses
Treat intermittent claudication
There are 2 classes of indirect thrombin inhibitors
Heparin-like agents
Xa inhibitors
Heparin-like agents MOA
Accelerate the effects of antithrombin on coagulation factors IIa and Xa by increasing the rate of the antithrombin III-coagulation factor reaction
Xa inhibitors do NOT require endogenous antithrombin to produce their effects but ___ do.
Heparin-like agents
Heparin-like agents are administered ___ and have a ___ onset of action.
Parenterally (IV)
Rapid
UFH
MOA
Half life
Cleared by
High molecular weight heparin
- mainly inhibits IIa and Xa
- 90 min
- reticuloendothelial system
LMWHs Examples MOA Half life Administered _ Cleared by _
Low molecular weight heparin
- enoxaparin, dalteparin, tinzaparin
- mainly inhibit Xa
- 4-5 hours
- IV or subcutaneously
- Kidney
LMWH vs UFH
LMWH have less chance of non-hemorrhagic side effects AND actions are predictable AND monitoring aPTT and platelet number is not required
Fondaparinux (sulfate pentasaccharide) is a synthetic agent that mainly inhibits ____ (and this activity is higher than that of ___). Half life is ___ and it is cleared by the ____. It is administered ___
Xa LMWH 17 hours Kidneys Subcutaneously
___ are the drug of choice for prophylaxis of DVT and PE because they are safe and convenient
LMWHs
___ should be initiated in all patients with confirmed acute PE
Parenteral anticoagulant therapy
Bleeding is a major side effect for ___, especially in elderly women and those with renal failure
Heparin-like agents
Heparin antidote
Protamine sulfate
Contraindications for heparin-like agents
Recent brain/eye/spinal cord surgery
Lumbar puncture
Regional anesthetic block
Coagulation abnormalities
Xa inhibitors
Examples
Route
Metabolism
Rivaroxaban Apixaban Edoxaban *all oral *CYP3A4/p-gp
Xa inhibitors
Uses
Prevent DVT, PE, stroke (in pts with nonvalvular a fib)
Irreversible direct thrombin inhibitors
Lepirudin (renal)
Bivalirudin (renal)
Argatroban (liver)
*IV
Reversible direct thrombin inhibitor Route Prodrug or not? Elimination Half life Metabolism
Dabigatran Oral Prodrug Urine 12-17 hours P-gp
Clinical uses of dabigatran
Primary and secondary prevention of DVT, PE, stroke, and systemic embolism in patients with non-valvular a fib
*no INR monitoring required
Dabigatran antidote
Idarucizumab
Warfarin
MOA
Inhibits synthesis of vitamin K dependent coag factors (II, VII, IX, X, Protein C, and Protein S) by suppressing vitamin K reductase
Warfarin is administered ___ and has ___% bioavailability. It has a ___ onset of action
Orally
100%
Slow
Warfarin
Uses
Primary and secondary prevention of DVT, PE, and thromboembolism associated with a fib, MI, and artificial heart valves
-also for recurrence of DVT or PE
Contraindications for warfarin
Pregnancy
Warfarin antidote
- Vitamin K
- Fresh frozen plasma
- Prothrombin complex concentrates
- recombinant factor VIIa
Fibrinolytic antidote
Aminocaproic acid
___ can be used to treat heparin-induced thrombocytopenia
Lepirudin
Argatroban
