Antiplatelets & anticoagulants Flashcards
What is Aspirin used for
Primary prevention of ischemic stroke, TIA, angina, coronary stenting, MI
Clot risk reduction in TKA/THA
DAPT w/ clopidogrel after CABG, PCI, TIA, stroke
What is the mechanism of action for Aspirin
Irreversible inhibition of COX-1-> an enzyme required by platelets to synthesize TXA2
What are the pharmacokinetics of Aspirin
Oral admin
Rapidly hydrolyzed by liver, excreted by kidneys
effects last for lifetime of platelets
What are the contraindications of Aspirin
GI bleeding
Hemorrhagic stroke
Tinnitus
*consider using PPI w/ ASA for GI bleeding
When is Clopidogrel used
First line anti platelet therapy
Prevents further atherosclerotic events in MI, ACS, PAD, coronary angioplasty, unstable angina
What is the MOA for clopidogrel
Irreversibly blocks P2Y12 ADP receptor on platelet surface
Decrease ADP-stimulated aggregation
What are the pharmacokinetics of Clopidogrel
Oral admin
Prodrug that undergoes hepatic CYP metabolism for active form
Reduced effectiveness in patients who are poor metabolizers
What are the contraindications / side effects of clopidogrel
Abdominal pain
dyspepsia
Diarrhea
Rash
Thrombotic thrombocytopenia purpura
*use with caution in drugs like omeprazole
What is Ticagrelor used for
Secondary prevention of atherothrombotic events in patients with ACS
*used instead of clopidogrel in patients who are poor metabolizers
What is the MOA of Ticagrelor
Reversibly blocks P2Y12 ADP receptors on platelet surface
What is the pharmacokinetics for ticagrelor
Oral admin
rapid onset (1-3 hours)
Has loading dose
What are the side effects. / contraindications of ticagrelor
Bleeding
abdominal pain
dyspepsia
diarrhea
rash
What is prasugrel used for
ACS
Secondary prevention of MI
Use with aspirin
*not routinely used
What is the MOA of pasugrel
Irreversibly blocks P2Y12 ADP receptors on platelet surface
*decrease platelet aggregation
What are the pharmacokinetics of Pasugrel
Oral admin
Effects last for lifetime of platelets
What are the side effects of pasugrel
Bleeding
abdominal pain
dyspepsia
diarrhea
rash
What is ticlopidine used for
TIA
Pts. with hx of stroke
*DISCONTINUED IN 2015
What is the MOA of ticlopidine
Blocks P2Y12 ADP receptors on platelet surface-> decrease aggregation
What are the side effects of Ticlopidine
Thrombocytopenia
agranulocytosis
TTP
How often does a CBC need to be done while on Ticlopidine
Every 2 weeks for 4 months
What is the primary indication for antiplatelet agents
Prevention of thrombosis in arteries
What is DAPT
Dual anti platelet therapy
What is ACS
Acute coronary syndrome
*blood supplied to the heart is suddenly blocked (MI)
What is Virchow’s Triad
Stasis
Defects in hemostatic mechanism
Endothelial injury
What forms the basis of clot formation
Fibrin
What is the simplified explanation of the clotting cascade
Conversion of prothrombin to thrombin which converts fibrinogen to fibrin
What fibrinolyzes the clot once the area of injury has stabilized
Plasmin (tPa)
What drugs are fibrinolytic
tPa
Anistreplase
Urokinase
Reteplase
Alteplase
What are P2Y12 ADP receptor inhibitors
Clopidogrel
Prasugrel
Ticlopidine
Ticagrelor
GP2B/3A receptor inhibitors
Abcixamab
Tirofiban
Eptifbatide
What are phosphodiesterase inhibitors
Dipyridamole
Cilostezol
What operations do you discontinue ASA 81typically
Intracranial
Intramedullary
Posterior eye surgery
What is a PPI
proton pump inhibitor
-Omeprazole
What are the anticoagulation antidotes
Protamine Sulfate
Vitamin K
Idarucizumab
What are direct oral anticoagulant drugs
Thrombin inhibitors
-Dabigatran
-Argatroban
Factor Xa inhibitors
-Rivaroxaban
-Apixaban
-Fonduparinux
What is the most significant side effect of unfractionated heparin
HIT
Heparin induced thrombocytopenia
What are examples of low molecular weight heparin
Enoxaparin
Dalteparin
Tinzaparin
What drugs increase the activity of Warfarin
ASA
Heparin
Antibiotics
What drugs decrease Warfarin activity
Vitamin K: Promote clotting factor synthesis
Cholestyramine: reduced absorption
Barbituates / phenytoin : Induction of metabolic enzymes
What does DOAC stand for
Direct
Oral
Anti-
Coagulants
What is Dipyramidole used for
Secondary stroke prevention
always combined with ASA
What is the MOA of Dipyramidole
Inhibits platelet adenosine deaminase phosphodiesterase which inhibits platelet aggregation and causes vasodilation
What are the side effects of Dipyramidole
Bleeding
dizziness
GI upset
rash
orthostatic hypotension
What is cilostazol used for
Intermittent claudication in legs in PVD
What is the MOA of Cilostazol
Binds to phosphodiesterase so cAMP cannot be broken down.
cAMP levels increase which inhibits platelet aggregation and causes vasodilation.
Increase HDL cholesterol and decrease TG
What is the pharmacokinetics of cilostazol
Oral admin
takes up to 12 weeks to develop but will reverse quickly in 48hours after drug withdrawal.
Metabolized by CYP3A4
What are the side effects of cilostazol
HA
GI upset
*contraindicated in heart failure
What is Abciximab used for
Humanized monoclonal antibody
preferred GP antagonist
used short term to prevent ischemic events in patients with ACS and those undergoing PCI
What is the MOA of Abciximab
Binds to platelets around GP 2b/3a receptors and prevents the receptors from binding to fibrinogen
What is the pharmacokinetics of Abciximab
IV bolus and then IV infusion
peak effect in 30min, persists for 24 hours
What are the side effects of Abciximab
bleeding
What is eptifibatide and Tirofiban used for
Short term to prevent thrombotic CV events
NSTEMI w PCI
interchangeable with Tirofiban
What is the MOA of eptifibatide and Tirofiban
Selective and reversible inhibition of GP 2b/3a receptors
What is unfractioned heparin used for
prevention of thromboembolism esp. when rapid anticoagulant is needed
does NOT cross placenta (preferred use in pregnancy)
adjunct therapy in acute MI
What is the MOA of unfractioned heparin
Binds to and activates antithrombin which inactivates thrombin, factor 9 and factor 10
increases antithrombin activity 1000 fold
What is the pharmacokinetics of unfractioned heparin
IV / Sub Q
Anticoagulant effects develop w/in a min
Dosing adjustment made based on PTT
What are side effects for unfractioned heparin
Bleeding
hyperkalemia*
HIT
Osteoporosis
What are the contraindications of unfractioned heparin
Pts. with uncontrolled bleeding
Thrombocytopenia
Surgery of Eye, brain, or spinal cord
Avoid with NSAID use
When is enoxaparin used (Low molecular weight heparin)
DVT/PE treatment
DVT prophylaxis in TKA/THA & abd. surgery
safe in pregnancy
What in the MOA for enoxaparin
Preferentially inactivate factor 10
What are the pharmacokinetics of enoxaparin
Sub Q
1/2t= 4.5-7hours
dosing is weight based
*also adjust for low creatinine clearance (<30)
What are the side effects of enoxaparin
Bleeding (less than heparin)
Thrombocytopenia
What is the antidote for Enoxaparin
protamine sulfate
What is Dalteparin used for
DVT/PE treatment
DVT prophylaxis in TKA/THA/abd surgery
*used primarily in patients with malignancy
What is the MOA of Dalteparin
Preferentially inactivates factor 10
What are the pharmacokinetics of Dalteparin
Sub Q
1/2t = 3-5 hours
Adjust for low creatinine clearance (<30)
What are the side effects of Dalteparin
Bleeding
Thrombocytopenia
peripheral edema
When is Tinzaparin used
DISCONTINUED IN 2011
When is Warfarin used
To prevent thrombosis but is inappropriate in emergencies (use for long term prophylaxis)
Standard prevention in strokes
*INR needs to be higher in those with a mechanical valve
What is Warfarin being replaced by as the standard for stroke prevention
DOACs
What is the MOA of Warfarin
Inhibits reactivation of vitamin K, which prevents activation of factors 2, 9,10, VII which prevents fibrin clot formation
What are the pharmacokinetics of warfarin
Takes 5 days to reach therapeutic level
can cross placenta
metabolized by CYP
Narrow TI
INR must be monitored
What are the side effects of Warfarin
Bleeding
What are the contraindications with warfarin
Pregnancy
breastfeeding
Thrombocytopenia
severe bleeding
Vit K deficiency
Liver disease
alcoholism
What is the antidote for Warfarin
Vitamin K
What are the DOAC drugs
Dabigatran
Argatroban (not actually oral)
Apixaban
Rivaroxaban
When is Dabigatran used
Prevention of stroke and systemic embolism in patients with nonvalvular afib
TKA/THA DVT and PE
What is the MOA of Dabigatran
Binds to thrombin and inhibits conversion of fibrinogen to fibrin
What are the pharmacokinetics of Dabigatran
Oral admin
Not highly protein bound, eliminated via kidneys
What are the side effects of Dabigatran
Bleeding
GI upset
D/c can cause rebound thromboses
What is the antidote for Dabigatran
Idarucizumab
When is Argatroban used
Prophylaxis of thromboses and and treatment of HIT
Can be used in PCI
What is the MOA of argatroban
Binds to thrombin and inhibits conversion of fibrinogen to fibrin
What are the pharmacokinetics of Argatroban
Continuous IV infusion (inpatient only)
Treatment monitored by measuring PTT
Dose adjust in patients with hepatic impairment
What are the side effects of argatroban
Hemorrhage
allergic reaction
When is apixaban used
DVT/PE prevention after TKA/THA
Stroke prevention in non-valvular afib
What is the MOA of apixaban
Binds to factor 10 and inhibits the production of thrombin
What are the pharmacokinetics of apixaban
Primarily metabolized by CYP3A4
2x/daily
What are the side effects of apixaban
Bleeding
When is Rivaroxaban used
DVT/PE prevention in non-valvular afib
What is the MOA of Rivaroxaban
Binds to factor 10 to inhibit the production of thrombin
What are the pharmacokinetics of Rivaroxaban
Rapid onset
fixed dose, 1x/daily
No INR monitoring
What are the side effects of Rivaroxaban
Bleeding (lower than warfarin)
Highest bleeding risk of the factor 10 inhibitors
Avoid in patients with severe renal impairment
unsafe in pregnancy
When is fonduparinux used
Prevention of DVT after orthopedic surgery
Treatment of DVT/PE
Slightly more effective that enoxaprin
What is the MOA of fonduparinux
Binds to antithrombin 3 and inhibits factor 10
What are the pharmacokinetics of Fonduparinux
Sub Q, fixed dose
No lab monitoring
Anticoagulation may persist 2-4 days after the last dose
What are the side effects of fonduparinux
Slightly higher bleeding risk than enoxaprin
Bleeding risk increases with age, renal impairment, and low body weight
When is protamine sulfate used
Antidote for heparin and low molecular weight heparin overdose
When is Vitamin K used
Antidote for warfarin overdose
When is Idarucizumab used
dabigatran OD
What is the MOA of protamine sulfate
Multiple positively charged groups bond ionically with negative groups on heparin to devoid anticoagulant activity
What are the pharmacokinetics of protamine sulfate
Admin by slow IV
Neutralization of heparin happens immediately and will last 2 hours
What is the MOA of vitamin K
Antagonizes warfarins actions and can thereby reverse the warfarin induced inhibition of clotting synthesis
What is the MOA of Idarucizumab
Monoclonal antibody fragment that binds to dabigatran
What is the pharmacokinetics of Vitamin K
Small oral doses
What is the pharmacokinetics of Idarucizumab
IV admin
