Anticoagulants, antiplatelets, and fibrinolytics Flashcards
ADP and P2Y12 inhibitors
Clopidogrel
Prasugrel
Ticagrelor
Ticlopidine - not in US (aplastic anemia)
Mechanism of ADP and P2Y12 inhibitors
Block ADP receptors which lead to inactivation of P2Y12 receptors, leading to an increase in cAMP to inhibit platelet aggregation
Clinical uses of ADP and P2Y12 inhibitors
Treatment of ACS
Stroke prevention
Dual antiplatelet therapy
Adverse effect of ADP and P2Y12 inhibitors
Bleeding
GP IIb/IIIa inhibitors
Abciximab
Tirofiban
Eptifibatide
Mechanism of GP IIb/IIIa inhibitors
Inhibit binding of fibrinogen to IIb/IIIa receptors to prevent platelet aggregation
Clinical uses of GP IIb/IIIa inhibitors
ACS
PCI
Adverse effect of GP IIb/IIIa inhibitors
Bleeding
Platelet adenosine uptake inhibitor that works by inhibiting phosphodiesterase
Dipyridamole
Clinical uses of dipyridamole
Thromboembolism prophylaxis
Pharmacologic cardiac stress test
PDE3 inhibitor that inhibits phosphodiesterase for an antiplatelet action
Cliostazol
Use of cliostazol
Intermittent claudication (PVD)
Protease-activated receptor 1 (PAR-1) inhibitor that inhibits platelet aggregation induced by thrombin and thrombin receptor agonist peptide (TRAP)
Vorapaxar
Clinical use of vorapaxar
Thrombotic event prevention
Adverse effects of vorapaxar
Bleeding
Depression
Rash
Thromboxane A2 (TXA2) inhibitor that irreversible acetylates COX1 receptors in platelets
Aspirin
Prophylactic use of aspirin
MI and CVA
Adverse effects of aspirin
GI upset
Bleeding
Vit K antagonist that inhibits the hepatic synthesis of vit K clotting factors (II, VII, IX, and X) by blocking the gamma-carboxylation of clotting factors
Warfarin
Bleeding values affected by warfarin use
INR and PT –> extrinsic pathway
Indication for warfarin use
Ambulatory anticoagulation
Contraindication of warfarin
Pregnancy –> crosses placenta –> teratogenic –> bone defects
Adverse effects of warfarin
Bleeding
Skin necrosis
Purple toe syndrome (3-8 wks)
Increased risk for developing skin necrosis with warfarin use
Pts with decreased protein C
Antidote to warfarin
Vit K1 (phytonadione)
Activates the plasma antithrombin III by enhancing serine protease activity to cause inactivation of clotting factors IIa, IXa, Xa, XIa, and XIIa
Heparin
Bleeding values affected by heparin
PTT –> intrinsic pathway
Adverse effects of heparin
Heparin induced thrombocytopenia (HIT)
Osteoporosis
Antidote to heparin
Protamine sulfate
Low molecular weight heparins with a higher half-life than heparin and less risk of thrombocytopenia. Higher activity against factor X and no impact on PT or PTT.
Enoxaparin
Dalteparin
Contraindication of enoxaparin
Prosthetic valve
Synthetic heparinoid with selective antithrombin III mediated Xa inhibition. Safer to use in heparin induced thrombocytopenia.
Fondaparinux
Recombinant hirudin obtained from yeast cells with direct thrombin inhibitory action
Lepirudin
Synthetic derivative of hirudin with direct thrombin inhibitory action
Bivalirudin
Indications for use of hirudin family drugs
Prevent thrombosis in pts with unstable angina and acute MI
Adverse effect of the hirudin family of drugs
Bleeding
Synthetic direct thrombin inhibitor indicated for use in treatment of thrombosis in pts with HIT
Argatroban (IV)
First oral direct thrombin inhibitor used to reduce risk of stroke in A fib and prevent thrombotic complications after joint replacement surgeries.
Dabigatran/Pradexa
Adverse effects of dabigatran/Pradexa
Bleeding
Gastritis-like symptoms
Interactions of dabigatran/Pradexa
Substrate for P-glycoprotein –> contraindicated in Pgp inducers (rifampin)
Caution with Pgp inhibitors (verapamil, amiodarone, clarithromycin)
Active factor Xa inhibitors
Apixaban/Eliquis
Rivaroxaban/Xarelto
Uses of apixaban
In A fib to reduce stroke risk
Prevention and treatment of venous thromboembolism
Uses of rivaroxaban
DVT
Blood clots
PE
After knee replacement
Adverse effect of active factor Xa inhibitors
Bleeding
Indications for anticoagulant therapy
Thromboembolic disorders –> DVT, PE, A fib
Unstable angina undergoing PCI
Only anticoagulant approved for use with synthetic valves
Warfarin
General contraindications for anticoagulant therapy
Hypersensitivity
Underlying coagulation disorder
Ulcer disease
Severe thrombocytopenia
Active bleeding
General adverse reactions to anticoagulant therapy
Hyperlipidemia
Thrombocytopenia
Pain at site of injection
Spinal and/or epidural hematoma
Heparin goal –> bleeding values
PTT > 1.5-2.5x normal
Normal PTT of 21-35 sec
Warfarin goal –> bleeding values
INR > 2.5x normal
Normal INR is 1
Clinical uses of fibrinolytics/thrombolytics
Acute MI
Acute PE
DVT
Thomboembolic stroke
Drug class that works by activating conversion of plasminogen to plasmin, causing lysis of fibrin clot to degradation products
Fibrinolytics/thrombolytics
Serine protease inhibited by alpha-2 antiplasmin
Plasmin
Tissue plasminogen activators –> recombinant DNA and clot specific
Altepase
Reteplase
Tenecteplase
Protein obtained by beta-hemolytic strep that can be used as a non-specific fibrinolytic
Streptokinase
Adverse effects of streptokinase fribinolytic
Allergic reaction
Hypotension
Decreased antibody activity after recent use
Prodrug of isolated streptokinase that acts as a slow release
Anistreplase
Fibrinolytic enzyme obtained from human neonatal kidney only approved for use in PE
Urokinase
Adverse effects of fibrinolytic therapy
Bleeding and hemorrhage –> additive
Contraindications of fibrinolytic therapy
Serious GI bleed
Active bleeding or hemorrhagic disorder
Surgery within 10 days
Aortic dissection
Antidote for fibrinolytic therapy
Aminocaproic acid
Adverse effects of aminocaproic acid
Thrombosis
Hypotension
Arrhythmias
Anti-fibrinolytic drug used to treat heavy menstrual bleeding
Tranexamic acid
Increased risk factors for thrombotic adverse effect with tranexamic acid
Obese
Cigarette smoking
OCP
