Antiplatelet Agents Flashcards
Which drugs affect hemostasis?
- Heparin-like
- Oral agents
- warfarin
- direct acting IIa and Xa inhibitors - Antiplatelet agents
- aspirin
- clopidogrel
- GP inhibitors (angioplasty) - Medical devices
What drugs affect thrombolysis?
Plasminogen activators
- alteplase
What is the goal of anticoagulation?
To diminish the activity of Factors Xa and IIa (thrombin)
What are examples of antithrombin III catalysts??
- heparin
- enoxaparin
- fondaparinux
What are examples of thrombin inhibitors?
- dabigatran
- rivaroxaban
- apixaban
What is an inhibitor of clotting factor synthesis?
warfarin
What’s the difference between fractionated and unfractionated heparin?
unfractionated = larger
fractionated = smaller
What is the pH of heparin?
acidic
made from porcine intestine or bovine lung
Antithrombin III catalysts MOA
Activate anti thrombin III so that it can bind to and inactivate factors IIa and Xa clotting factors.
True/false: heparin is NOT consumed in the reaction (binding to antithrombin III)
True. It is NOT consumed. It is a catalyst
Unfractionated heparin MOA
accelerates the reaction. Can bridge thrombin/antithrombin molecules, which speeds up the reaction of ATIII and IIa
LMW heparin MOA
No bridge. Can accelerate the interaction of ATIII with Xa.
Fondaparinux MOA
Pentasaccharide that binds to ATIII, inhibits Xa activity.
Which of the heparins requires routine monitoring?
heparin
True/false: heparin does not cross the placenta.
True
Heparins: adverse effects
BLEEDING
hypersensitivity
thrombocytopenia
What is the best way to monitor the anticoagulant action of heparin?
aPTT (increase)
maintain 2x control time
What is Heparin-induced thrombocytopenia? (HIT)
Antibodies againsed heparin-platelet factor 4 complexes. Bind to Fc receptors on adjacent platelets >> aggregation. = antibody mediated thrombocytopenia with paradoxical thrombosis
True/False: warfarin is contraindicated in HIT.
True.
A direct thrombin inhibitor is preferred, fondaparinux or argatroban.
Contraindication for heparin
- hypersensitivity
- active bleeding
- threatened abortion
- infective endocarditis
- surgical procedures
What is the heparin antagonist?
protamine sulfate
ion pairs with heparin to form a stable complex. BE CAUTIOUS: excess PS has anticoagulant activity. Adverse effects = dyspnea, bradycardia, hypotension
Indications for LMW heparin
- DVT, clots
- CONTRAINDICATED in HIT
Indications for Fondaparinux
- PE, DVT
- thromboprophylaxis for hip/knee surgery
- use for HIT
Thrombin inhibitors MOA
Agents that bind to and directly inhibit the activity of key clotting factors.
Warfarin MOA
decreases synthesis of active coagulation factors
inhibits addition of the gamma-carboxy groups to the clotting factors
= inactive factors
What is warfarin’s MOA in relation to vitamin K?
It blocks the enzyme VKORCI, which is key to recycling (reduction) of vitamin K.
What is important to know about the time frame for using warfarin clinically?
It takes time, 8-12 hrs for the drug to act; full activity takes several days.
Warfarin Adverse effects
- BLEEDING
- Fetal hemorrhage; abn bone formation
- Inhibition of protein C and S >> procoagulant states
Vitamin K and Warfarin
Warfarin = structural analog of vit. K (isomers)
S form is 4x more active
Warfarin drug interactions
metabolized by CYP2C9
Vitamin K-large doses can reverse warfarin action
Dabigatran
Rivaroxaban
Apixaban
orally direct acting inhibitors
Dabigatran
Prodrug >> hydrolysis
Adverse effects = BLEEDING (esp GI), slightly higher MI risk
Drug interactions: p-glycoprotein transport (ketoconazole + rifampin)
Are there antidotes to dabigtran and rivaroxaban?
NO
*also very expensive drugs
Rivaroxaban
Adverse effect = BLEEDING
Drug interactions: p-glycoprotein and Cyp 3A4
Desirudin MOA
Direct acting thrombin inhibitor
- no need for ATIII
- one to one complex with thrombin*
was lepirudin
Bivalrudin MOA
20 AA direct inhibitor
Argatroban MOA
must be IV
blocks catalytic site of thrombin (reversible)
use in HIT
Abciximab MOA
blocks GP IIB/IIIa receptors
- an integrin, receptor for fibrinogen and vWF
adjunctive for angioplasty
Clopidogrel (&prasugrel) MOA
Antiplatelet
ADP pathway: P2Y1 and P2Y12 receptors activated at the same time >> activate platelets
Clopidogrel inhibits activation P2Y12 irreversibly
**alternative for apteints who cannot tolerate aspirin (no effect on prostaglandin pathway)
What happens when you combin clopidogrel and aspirin?
synergy
What is unique about the metabolism of heparin?
metabolized by the RES
What is unique about the metabolism of dabigatran?
Is NOT metabolized
renal excretion
Prasugrel
newer member of class
contraindicated in cerebrovascular disease
Adverse effect of Clopidogrel
rash, diarrhea, abdominal pain, dyspepsia, bleeding
