Anticoagulants, Antithrombotics & Thrombolytic Drugs Flashcards
Heparine Sulfate (UFH)
Anticoagulant
- Linear polysaccharide delivered parenterally. Bovine or porcine source.
- Catalyzes antithrombin activity by direct binding. Inhibits IIa, IXa, Xa.
- Used to treat acute DVT or PE, prophylaxis of venous thrombosis and DIC and arterial thrombosis
- Side Effects: bleeding, allergy, thrombosis, osteoporosis, HIT-heparin induced thrombocytopenia- systemic hypercoagulable state following > 7 day treatment of heparin. Never administer intramuscularly
- Monitor PTT
- Clearance by RES (saturatable) and kidney (non-saturatable)
Rivaroxaban
Anticoagulant
- Orally admin once daily factor X inhibitor
- Maximal effect 4 h
- Liver, Renal and Fecal biliary clearance
- No monitoring, short half life, no reversal agent
Warfarin
Antigoagulant
- Inhibits vitamin K metabolism which disrupts gamma carboxylation of several glutamate residues in factors II, VII, IX, X, C, S. C & S drops first, so does with heparin at first. No degradation of factors. Effect dependent on factor half life.
- Side Effects: bleeding, skin necrosis, teratogenesis
- INTERACTS WITH NUMEROUS OTHER DRUGS, DISEASES, DIETS!
- Liver and kidney clearance
- Monitor therapy with INR and PT
- Add Menadione (Vit K), FFP and factor VIIa to counteract
Protamine
Heparin Antagonist
*Cationic protein binds to heparin to form stable ion pair.
Menadione
Vitamin K, Warfarin Antidote
Dalteparin
LMW Heparin
- Enhances antithrombin action on factor X
- Metabolized by kidney, so use caution in pts with renal disease
- Doesn’t require careful monitoring
- Protamine partially effective inhibitor
Enoxaparin
LMW Heparin
- Enhances antithrombin action on factor X
- Metabolized by kidney, so use caution in pts with renal disease
- Doesn’t require careful monitoring
- Protamine partially effective inhibitor
Fondaparinux
LMW Heparin
- Pentasaccharide with added methyl groups
- Enhances antithrombin action on factor X
- Metabolized/cleared by kidney, so use caution in pts with renal disease
- Doesn’t require careful monitoring
- Protamine INEFFECTIVE
Argatroban
Direct Thrombin Inhibitor
- Small molecule administered IV due to short half life
- Hepatic clearance
- Selection based on clearance organ function
Bivalirudin
Direct Thrombin Inhibitor
- 20 aa peptide, admin IV
- Hepatic and Renal (20%) clearance
- Selection based on clearance organ function
Lepirudin
Direct Thrombin Inhibitor
- 65 aa peptide, admin IV
- Renal Clearance
- Selection based on clearance organ function
Dabigatran
Direct Thrombin Inhibitor
- Oral, effect within 2-3 h
- 80% renal clearance
- No monitoring
- Short half life
- No good reversal agent
- Side Effect: GI Bleeding
Tissue Plasminogen Activator (tPA)
Thrombolytic, human
- Shortest half life
- Used to treat MI, PE, or massive Venous thrombosis
- 1% Risk of intracranial hemorrhage
Streptokinase
Thrombolytic, bacterial
- Longest half life
- Used to treat MI, PE, or massive Venous thrombosis
- 1% Risk of intracranial hemorrhage
Urokinase
Thrombolytic, human
- Intermediate half life
- Used to treat MI, PE, or massive Venous thrombosis
- 1% Risk of intracranial hemorrhage
Abciximab
Antiplatelet Drug, Glycoprotein IIb/IIIa Inhibitor
- Monoclonal Ab
- Inhibit platelet IIb/IIIa receptor complex which acts as a receptor for fibrinogen, vitronectin and vWF
Aspirin
Antiplatelet Drug
*Inhibits synthesis of thromboxane A2 by irreversible acetylation of COX. Thromboxane A2 causes platelets to aggregate
*Most commonly used anti-platelet drug. Used to prevent TIA, stroke, MI, coronary restenosis following MI/Fibrinolytic Therapy/Bypass Grafting.
Side Effects: Excessive bleeding
Clopidogrel
Antiplatelet Drug, Thienopyridine Derivative
- Reduce platelet aggregation by irreversibly blocking P2Y12 receptor on platelets. No effect on PG metabolism.
- Used in pts undergoing coronary stent or pts who can’t tolerate aspirin.
- Fewer side effects than Ticlopidine
- Activated by CYP2C19, genetic test required to determine susceptibility
Prasurgel
Antiplatelet Drug, Thienopyridine Derivative
- Reduce platelet aggregation by irreversibly blocking P2Y12 receptor on platelets. No effect on PG metabolism.
- Used in pts who can’t tolerate aspirin.
- Unlike Clopidogrel, metabolized through hydrolysis. Decreases platelet aggregation more rapidly and in more individuals than Clopidogrel
Ticlopidine
Antiplatelet Drug, Thienopyridine Derivative
- Reduce platelet aggregation by irreversibly blocking P2Y12 receptor on platelets. No effect on PG metabolism.
- Used in pts undergoing coronary stent or pts who can’t tolerate aspirin.
- Side effects: diarrhea, nausea, dyspepsia, hemorrhage and rarely leukopenia
Tirofiban
Antiplatelet Drug, Glycoprotein IIb/IIIa Inhibitor
- Small molecule inhibitor
- Inhibit platelet IIb/IIIa receptor complex which acts as a receptor for fibrinogen, vitronectin and vWF
Eptifibatide
Antiplatelet Drug, Glycoprotein IIb/IIIa Inhibitor
- analogue of carboxy terminal of fibrinogen which mediates interactions with receptor
- Inhibit platelet IIb/IIIa receptor complex which acts as a receptor for fibrinogen, vitronectin and vWF
