Anticoagulants & thrombolytics-Mata Flashcards
Heparin
MOA: binds to endogenous antithrombin III and irreversibly inactives thrombin
- Given parenterally
- Speeds up antithrombin action 1000x
Unfractionated heparin
- Begins working immediately
- Used in combo w/thrombolytics for revascularization
- Does NOT cross placental barrier so ok for preggos
- IV or SC to avoid hematoma
- Speeds up activity on factor XA
- Prophylaxis for DVT
Low Molecular Weight (LMW) Heparin & Foundparinux
- Binds antithrombin and has same inhibitory effect on XA as unfractionated heparin
- More selective (no effect on thrombin)
- IV or SC (longer half-life after SC)
Heparin toxicity
- Increased bleeding time is common adverse effect of heparin and related molecules
- Can lead to hemorrhagic stroke
Protamine
- Lessens risk of serious bleeding w/heparin
Major Side Effects of Heparin
- Non-immune mediated Heparin–associated thrombocytopenia (HAT) Type I - common; direct run b/n heparin and platelets
- Immune-mediated Heparin-induced thrombovytopenia (HIT) Type II - FATAL
Rivaroxaban
- MOA: direct inhibitor of factor XA that inhibits both free and clot bound factor XA
- Uses: prophylaxis for DVT, reducing stroke risk
- Risk of thrombotic events upon premature discontinuation
Lepirudin
- Direct thrombin inhibitor
- Recombinant form of hirudin
- Alternative to heparin
- Irreversibly binds and inhibits free and fibrin bound thrombin
- Cons: prolonged half-life in renal compromised pts
Desirudin & Bivalirudin
- Direct thrombin inhibitor
- Modified forms of hirudin
- Bivalrudin also inhibits platelet activation
Direct thrombin inhibitors
Based on leech protein hirudin that directly binds to thrombin to prevent thrombin-mediated activation of fibrinogen and factor XIII
Argatroban
- Small molecule direct thrombin inhibitor (binds only to active site of thrombin)
- Used for treatment of patients with heparin-Induced thrombocytopenia (HIT)
- Safe to be given in renal insufficiency (excrete via biliary route)
Dabigatran
- Small molecule direct thrombin inhibitor (binds only to active site of thrombin)
- No need to monitor blood levels
- Greater predictive PK and PD
- No dose adjustments
- No significant drug-interactions
Warfarin
- MOA: inhibits Vitamin K epoxide reductase needed for coagulation cascade
- Affects factor II, VII, IX & X
- Mimics Vitamin K (Vit K can also reverse it)
- SE: bleeding, transient period of hypercoagulaility, inhibition of protein C
- Narrow therapeutic range
Tissue Plasminogen Activator (tPA) (aka - Thrombolytic Agents)
- An enzyme that binds to fibrin in a newly formed clot and directly converts plasminogen to plasmin
- Toxicity can cause cerebral hemorrhage
- Increases risk of bleeding with warfarin, heparin, aspirin
Alteplase
- Thrombolytic (fibrinolytic) Agent
- Normal human tPA
Reteplase
- Thrombolytic (fibrinolytic) Agent
- Mutated tPA w/similar effects but faster onset of action and longer duration of action
Tenecteplase
- Thrombolytic (fibrinolytic) Agent
- Mutated form of tPA w/longer half life
Anistreplase
A preformed complex of streptokinase and plasminogen
Platelet Activation
Mediated by release of soluble platelet factors (ADP, TxA2)
Aspirin
- Irreversible inhibitor of COX1 (which makes TxA2)
- Efficacy is not dose related
- High doses can lead to GI bleeding and ulceration
- So prescribe baby aspirin!
Thienopyridines
- MOA: irreversible inhibitors of platelet ADP receptors
- BBW: bleeding
Ticlopidine
- Thienopyridine
- Converts to thiol metabolites that accumulate (therefore delay in action)
- Takes 8-11 days for max effect
- Shorten delay w/aspirin or loading dose
- BBW: life threatening hematological adverse runs including neutropenia, TTP, and aplastic anemia
Clopidogrel
- Thienopyridine
- Metabolized by CYP2C19
- Poor metabolizers may show higher rates of CV SEs
- BBW: diminished effectiveness in poor metabolizers
Prasugrel
- Thienopyridine
- More effectively metabolized than clopidogrel so greater P2Y ADP antagonism
- Metabolized via CYP3A4
Ticagelor
- Thienopyridine
- Parent drug and major metabolite reversibly interact w/P2Y12 ADP receptor
- Both parent and metabolite are equipotent
- Metabolized via CYP3A4
- BBW: bleeding risk
Abciximab
- Platelet glycoprotein IIb/IIIa receptor blocker
- MOA: bind to IIb/IIIa and prevent interaction w/fibrinogen
- Chimeric mouse/human monoclonal Ab
Eptifibatide & Tirofiban
- Platelet glycoprotein IIb/IIIa receptor blockers
- MOA: bind to IIb/IIIa and prevent interaction w/fibrinogen
- Small molecule inhibitors
Phosphodiesterase Inhibitors
2 MOAs:
- Block uptake of adenosine which stimulate platelet adenylyl cyclase
- Inhibits platelet phosphodiesterase which leads to increased intracellular cAMP and decreased platelet aggregation
Cilostazol
- Phosphodiesterase Inhibitor
- Used to treat intermittant claudication (manifestation of peripheral arterial disease)
- Not for pts w/CHF!
Dipyridamole
- Phosphodiesterase Inhibitor
- Used + Warfarin to prevent thrombus on prosthetic heart valves
- Used + Aspirin to lower incidence of thrombotic diathesis
Fibrinolytic Inhibitors
MOA: lysine analog that blocks plasmin fibrin interaction
Aminocaproic Acid
- Fibrinolytic Inhibitor
- Used to reduce bleeding in hemophiliacs after prostatic surgery or tooth extractions
- Thrombi that form during drug treatment do not get lysed
Tranexamic Acid
- Fibrinolytic Inhibitor
- Used to control heavy menstrual bleeding
Vitamin K
- Hemostatic agent
- MOA: essential cofactor required in γ-carboxylation of several clotting factors (II, VII, IX and X)
- Used in reversing bleeding episodes induced by oral anticoagulants
- Caution: fast IV infusion can lead to dyspnea, chest pain and death
Which drugs are anticoagulants? (4)
- Heparin
- Unfractionated Heparin
- LMW Heparin & Foundparinux
- Rivaroxaban
Which drugs are Direct Thrombin Inhibitors? (4)
- Lepirudin
- Desirudin & Bivalrudin
- Argatroban
- Dabigatran
Which drugs are Thrombolytic Agents? (3)
- Ateplase
- Reteplase
- Tenecteplase
Which drugs are Thienopyridines? (4)
- Ticlopidine
- Clopidogrel
- Prasugrel
- Ticagelor
Which drugs are Platelet Glycoprotein IIb/IIIa receptor blockers? (2)
- Abciximab
2. Eptifibatide & Tirofiban
Which drugs are Phosphodiesterase Inhibitors? (2)
- Cilostazol
2. Dipyridamole
Which drugs are Fibronlytic Inhibits? (3)
- Aminocaproic Acid
- Tranexamic Acid
- Vitamin K
