Anticoagulants, Thrombolytic, Coagulant Agents Flashcards
What are the oral antiplatelet agents?
Aspirin, NSAIDs, Ticlopidine (Ticlid), Clopidogrel (Plavix), Prasugrel (Effient), Ticagrelor (Brilinta)
What is the MOA of Aspirin?
Irreversible COX inhibitor; reduces prostaglandin synthesis (and TXA2) > less platelet aggregation
When would you use Aspirin?
Preventing subsequent heart attack/stroke, coronary artery disease, history of coronary bypass operation or coronary angioplasty
What is the MOA of NSAIDs?
Reversible COX inhibitor; reduces prostaglandin synthesis > less platelet aggregation
When would you use NSAIDs?
Preventing subsequent heart attack/stroke, coronary artery disease, history of coronary bypass operation or coronary angioplasty
What are the contraindications of NSAIDs?
Aspirin is preferred due to irreversibility
What is the MOA of Ticlopidine (Ticlid)?
Inhibits platelet function (via induction of thrombasthenia-like state); irreversibly inhibits ADP-induced platelet fibrinogen binding and platelet-platelet interactions
When would you use Ticlopidine (Ticlid)?
Prevents stroke in patients with history of TIA or thrombotic stroke (if intolerant of or if aspirin fails); combo with aspirin to prevent coronary stent thrombosis
What are the ADRs of Ticlopidine (Ticlid)?
Nausea, dyspepsia, diarrhea (20%), hemorrhage (5%), leukopenia (1%), and TTP
What is the MOA of Clopidogrel (Plavix)?
Irreversible block/covalent binding of the ADP receptor on platelets; irreversibly inhibits platelet-fibrinogen and platelet-platelet interactions
When would you use Clopidogrel (Plavix)?
Unstable angina or non-ST-elevation acute MI (NSTEMI) in combo with aspirin; STEMI; recent MI, stroke, peripheral artery disease; cardiovascular conditions prone to clot formation
What are the ADRs of Clopidogrel (Plavix)?
TTP, rare neutropenia (preferred over ticlopidine)
What are the contraindications of Clopidogrel (Plavix)?
When using drugs that impair CYP2C19 function (CYP450 isoform needed for activation of drug)
What is the MOA of Prasugrel (Effient)?
Inhibits platelet activation and aggregation mediated by ADP receptor
When would you use Prasugrel (Effient)?
Unstable angina or non-ST-elevation acute MI (NSTEMI) in combo with aspirin; STEMI; recent MI, stroke, peripheral artery disease; cardiovascular conditions prone to clot formation
What are the ADRs of Prasugrel (Effient)?
Major and minor bleeding risk increased over clopidogrel
What are the contraindications of Prasugrel (Effient)?
Patients with TIA history or stroke due to increased bleeding risk
What is the MOA of Ticagrelor (Brilinta)?
Reversible antagonist of ADP receptor; does not require bioactivation > faster onset
When would you use Ticagrelor (Brilinta)?
Acute coronary synderomes in combo with low-dose aspirin
What are the ADRs of Ticagrelor (Brilinta)?
Increased non-cardiac surgical bleeding, shortness of breath at rest or after small exercise; chest pain; fast, slow, pounding, or irregular heartbeat
What are the injectable antiplatelet agents?
Abciximab (Reopro), Eptifibatide (Integrilin), Tirofiban (Aggrastat)
What is the MOA of Abciximab (Reopro)?
GpIIb/IIIa antagonist (chimeric monoclonal antibody against GpIIb/IIIa complex)
When would you use Abciximab (Reopro)?
Percutaneous coronary intervention and acute coronary syndromes
What are the ADRs of Abciximab (Reopro)?
Bleeding
What is the MOA of Eptifibatide (Integrilin)?
GpIIb/IIIa antagonist (cyclic peptide derived from rattlesnake venom); variant RGD motif; competes with fibrinogen for binding to GpIIb/IIIa; short half life
When would you use Eptifibatide (Integrilin)?
Percutaneous coronary intervention and acute coronary syndromes
What are the ADRs of Eptifibatide (Integrilin)?
Bleeding
What is the MOA of Tirofiban (Aggrastat)?
GpIIb/IIIa antagonist (peptidomimetic inhibitor with the RGD sequence motif)
When would you use Tirofiban (Aggrastat)?
Non-ST elevation acute coronary syndrome (NSTE-ACS); short half life (continuous infusion)
What are the ADRs of Tirofiban (Aggrastat)?
Minor bleeding
What are the combined antiplatelet agents?
Dipyridamole (Persantine), Cilostazol (Pletal)
What is the MOA of Dipyridamole (Persantine)?
Inhibits adenosine uptake and inhibits cGMP phosphodiesterase (cGMP/cAMP inhibitory to platelet adhesion/aggregation) > vasodilation that also inhibits platelet function
When would you use Dipyridamole (Persantine)?
Little or no effect when alone; with aspirin > prevent cerebral ischemia; with warfarin > prophylaxis of thromboemboli for prosthetic heart valves
What are the ADRs for Dipyridamole (Persantine)?
Chest pain, angina exascerbation (IV), abnormal ECG, headache (IV), dizziness, ST-T changes; abdominal discomfort (oral); extrasystole
What is the MOA of Cilostazol (Pletal)?
Phosphodiesterase inhibitor; promotes vasodilation and inhibits platelet aggregation
When would you use Cilostazol (Pletal)?
Claudication (cramping pain in leg due to exercise bc of peripheral vascular disease)
What are the ADRs of Cilostazol (Pletal)?
Headache, diarrhea, abnormal stools, infection, rhinitis, pharyngitis, dizziness, palpitations, peripheral edema, back pain, dyspepsia
What are the contraindications for Cilostazol (Pletal)?
CHF of any severity
What are the injectable indirect thrombin inhibitors?
Heparin, Fondaparinux (Arixtra)
What is the MOA of Heparin?
IV/SQ; Enhances the activity of anti-thrombin III (AT-III) > inhibition of thrombin (IIa), IXa, Xa, XIa, and XIIa; high molecular weight heparin has high affinity for AT-III and IIa, IXa, Xa (mainly IIa/Xa); low molecular weight inhibits Xa (enoxaparin, dalteparin, tinzaparin) with less frequent dosing needed
When would you use Heparin?
In vivo: prevention and treatment of deep vein thrombosis, pulmonary embolism, arterial thrombosis; in vitro: hemodialysis, indwelling vascular catheters, lab blood samples
What are the ADRs of Heparin?
Unwanted bleeding (mucous membranes, open wounds, intracranial, GI), allergic rxns, hair loss; induced thrombocytopenia (HIT) in 1-4% > skin necrosis; long term use > osteoporosis and fractures (mineralocorticoid deficit)
What is the antidote for heparin?
Protamine sulfate (complexes with heparin) given as SC or IV; close monitoring needed; unfractionated heparin = PTT, or LMW heparin by anti-factor Xa assay
What is the MOA of Fondaparinux (Arixtra)?
IV/SQ; synthetic pentasaccharide of heparin; enhances the activity of AT-III; mimics active site of heparin that binds AT-III (only enhances AT-III inactivation of Xa > less thrombin formed)
When would you use Fondaparinux (Arixtra)?
DVT/acute PE (treatment and prophylactic) and acute coronary syndrome; predictable pharmacokinetics therefore no monitoring
What are the ADRs of Fondaparinux (Arixtra)?
Some cross-reactivity with heparin antibodies, some cases of HIT; anemia, fever, nausea, rash, constipation, edema headache, insomnia, vomiting
What are the injectable direct thrombin inhibitors?
Bivalirudin (Angiomax), Argatroban (Acova)
What is the MOA of Bivalirudin (Angiomax)?
IV; specific and reversible bivalent direct thrombin inhibitor; rapid on/off (25 min half life); inhibits platelet activation
When would you use Bivalirudin (Angiomax)?
With aspirin: unstable angina with patients undergoing percutaneous transluminal coronary angioplasty (PTCA), percutaneous coronary intervention (PCI) with provisional use of GpIIb/IIIa inhibitor, with or at risk of HIT/heparin-induced TTP and thrombosis syndrome (HITTS) undergoing PCI
What are the ADRs of Bivalirudin (Angiomax)?
Back, general pain; nausea, hemorrhage (minor), headache, hypotension, injection site pain, insomnia, pelvic pain, hypertension, anxiety, vomiting, bradycardia, dyspepsia, abdominal pain, fever, nervousness
What is the MOA of Argatroban (Acova)?
IV (via infusion with short half life); thrombin inhibitor monitored with aPTT
When would you use Argatroban (Acova)?
HIT (with or without thrombosis), coronary angioplasty with HIT, monitored by aPTT (argatroban increases INR > difficult transition to warfarin)
What are the ADRs with Argatroban (Acova)?
GI bleeding, hematuria, chest pain, hemoglobin and hematocrit decrease, hypotension, dyspnea, fever, sepsis, cardiac arrest, diarrhea, nausea, groin hemorrhage, pain, urinary tract infection, ventricular tachycardia
What are the oral direct thrombin inhibitor?
Dabigatran Etexilate (Pradaxa)
What is the MOA of Dabigatran Etexilate (Pradaxa)?
Binds to and inhibits thrombin
When would you use Dabigatran Etexilate (Pradaxa)?
Prevent venous thromboembolic events in adults following total hip/knee replacement; non-valvular atrial fibrillation (over warfarin)
What is the antidote for Dabigatran Etexilate (Pradaxa)?
Idarucizumab (Praxbind): binds to dabigatran and its metabolites with higher affinity than dabigatran to thrombin > neutralization of anticoagulant effect
What are the oral anti-clotting factor agents?
Warfarin (Coumadin), Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Savaysa)
What is the MOA of Warfarin (Coumadin)?
Antagonist of vitamin K (decarboxylates to activate II, VII, IX, X, protein S and C); prevents reduction to allow for recycling
When would you use warfarin (Coumadin)?
Prevent or treat DVT or PE; for blood clots that may be caused by certain heart conditions, open-heart surgery, or after MI; monitoring needed via prothrombin time (PT)/INR
What are the ADRs of Warfarin (Coumadin)?
Unwanted bleeding (like heparin)
What are the contraindications of Warfarin (Coumadin)?
Pregnancy > teratogen (birth defects in bone)
What is the antidote for Warfarin (Coumadin)?
Vitamin K1 (Aquamephyton/Konakion 1)
What is the MOA of Rivaroxaban (Xarelto)?
Inhibits free Xa and clot-bound Xa prothrombinase activity; directly inhibits platelet aggregation induced by thrombin (bc reduces thrombin formation)
When would you use Rivaroxaban (Xarelto)?
Thromboembolism prevention after ortho surgeries; non-valvular atrial fibrillation (NVAF) prevention; treat and prevent DCT and PE
What is the MOA of Apixaban (Eliquis)?
Direct inhibitor of free and clot-bound Xa
When would you use Apixaban (Eliquis)?
Prevention of thromboembolism: to reduce risk of stroke, non-valvular atrial fibrillation, hip/knee replacement surgery; treatment of DVT or PE
What is the MOA of Edoxaban (Savaysa)?
Selective (direct) Xa-inhibitor
When would you use Edoxaban (Savaysa)?
Prevention of thromboembolism: ortho surgeries, patients with NVAF; treatment of DVT or PE: for patients initially treated with parenteral anticoagulant for 5-10 days
What are the specific thromboembolytic agents?
Streptokinase (Streptase), Urokinase (Abbokinase)
What is the MOA of Streptokinase (Streptase)?
Complexes with plasminogen > conformational change; activates free plasminogen > plasmin (systemic and not clot specific)
When would you use Streptokinase (Streptase)?
IV: PE with hemodynamic instability, severe DVT (superior vena caval syndrome), and ascending thrombophlebitis of iliofemoral vein with severe lower extremity edema; intra-arterially: peripheral vascular disease; within 6 hrs post symptomatic onset of acute MI; t-PAs also for acute ischemic stroke within 3 hrs symptom onset
What are the ADRs for Streptokinase (Streptase)?
Blurred vision, confusion, dizziness, faintness when getting up from lying or sitting position, fever sweating, unusual tiredness or weakness
What are the contraindications of Streptokinase (Streptase)?
Patients with antistreptococcal antibodies > fever, allergic rxns, resistance
What is the antidote for Streptokinase (Streptase)?
Aminocaproic Acid (Amicar)
What is the MOA of Urokinase (Abbokinase)?
Cleaves arg-arg 560-561 peptide bond in plasminogen > active plasmin (systemic)
When would you use Urokinase (Abbokinase)?
IV: PE with hemodynamic instability, severe DVT (superior vena caval syndrome), and ascending thrombophlebitis of iliofemoral vein with severe lower extremity edema; intra-arterially: peripheral vascular disease; within 6 hrs post symptomatic onset of acute MI; t-PAs also for acute ischemic stroke within 3 hrs symptom onset
What are the ADRs for Urokinase (Abbokinase)?
Bleeding, dizziness, headache, paralysis, difficulty breathing or swallowing
What is the antidote for Urokinase (Abbokinase)?
Aminocaproic Acid (Amicar)
What are the Tissue Plasminogen Activators (t-PAs)?
Alteplase (Activase), Reteplase (Retavase), Tenecteplase (TNKase)
What is the MOA of Alteplase (Activase)?
Binds to fibrin and activates bound plasminogen; cleaves arg-arg 560-561 bond of fibrin-bound plasminogen; inefficient at activating free systemic plasminogen (clot-specific)
When would you use Alteplase (Activase)?
IV: PE with hemodynamic instability, severe DVT (superior vena caval syndrome), and ascending thrombophlebitis of iliofemoral vein with severe lower extremity edema; intra-arterially: peripheral vascular disease; within 6 hrs post symptomatic onset of acute MI; t-PAs also for acute ischemic stroke within 3 hrs symptom onset
What are the ADRs of Alteplase (Activase)?
Similar to urokinase
What is the antidote for Alteplase (Activase)?
Aminocaproic Acid (Amicar)
What is the MOA of Reteplase (Retavase)?
Binds to fibrin and activates bound plasminogen; cleaves arg-arg 560-561 bond of fibrin-bound plasminogen; inefficient at activating free systemic plasminogen (clot-specific)
When would you use Reteplase (Retavase)?
IV: PE with hemodynamic instability, severe DVT (superior vena caval syndrome), and ascending thrombophlebitis of iliofemoral vein with severe lower extremity edema; intra-arterially: peripheral vascular disease; within 6 hrs post symptomatic onset of acute MI; t-PAs also for acute ischemic stroke within 3 hrs symptom onset
What are the ADRs for Reteplase (Retavase)?
Similar to Urokinase
What is the antidote for Reteplase (Retavase)?
Aminocaproic Acid (Amicar)
What is the MOA of Tenecteplase (TNKase)?
Binds to fibrin and activates bound plasminogen; cleaves arg-arg 560-561 bond of fibrin-bound plasminogen; inefficient at activating free systemic plasminogen (clot-specific)
When would you use Tenecteplase (TNKase)?
IV: PE with hemodynamic instability, severe DVT (superior vena caval syndrome), and ascending thrombophlebitis of iliofemoral vein with severe lower extremity edema; intra-arterially: peripheral vascular disease; within 6 hrs post symptomatic onset of acute MI; t-PAs also for acute ischemic stroke within 3 hrs symptom onset
What are the ADRs for Tenecteplase (TNKase)?
Similar to urokinase
What is the antidote for Tenecteplase (TNKase)?
Aminocaproic Acid (Amicar)
What is the anti-fibrinolytic agent?
Aminocaproic Acid (Amicar)
What is the MOA of Aminocaproic Acid (Amicar)?
Oral/IV; binds to lysine binding sites on plasminogen and plasmin; blocks the binding of plasmin to target fibrin; potent inhibitor of fibrinolysis
When would you use Aminocaproic Acid (Amicar)?
Antidote for steptokinase, urokinase, t-PA; to reverse excessive fibrinolysis states
What are the ADRs for Aminocaproic Acid (Amicar)?
Myopathy, muscle weakness, others undefined
What are the Specific coagulating agents?
Factors: VIII, IX, IX complex, VIIa, X, Vitamin K, Thrombin, Gelfoam, vWF (Vonvendi)
What is the MOA of Factor VIII?
Plasma precipitate (fresh/frozen) with 8-12 hr half life; human (Alphanate, Hemofil M, Koate-DVI, Monoclate-P); recombinant DNA (adynovate)
When would you use Factor VIII?
To treat hemophilia A
What is the MOA of Factor IX?
Purified human factor (heat treated from plasma): Alphanine SD, Mononine; recombinant: Benefix, Alprolix, Rixubis, Ixinity, Idelvion
When would you use Factor IX?
To treat hemophilia B
What are the ADRs of Factor IX?
Formation of circulating antibodies against factor IX
What is the MOA of Factor IX complex?
Recombinant DNA: Bebulin VH, Profilnine SD, Proplex T
When would you use Factor IX complex?
To treat hemophilia B
What are the ADRs of Factor IX complex?
Formation of circulating antibodies against factor IX
What is the MOA of Factor VIIa?
IV; activates factor X to Xa and factor IX to IXa; recombinant DNA (Novoseven, AryoSeven)
When would you use Factor VIIa?
To treat hemophilia A or B
What are the ADRs for Factor VIIa?
Fever, hemorrhage, hemarthrosis, decreased fibrinogen, hypertension; Black box warning: serious arterial/venous thrombotic and thromboembolic events post admin
What is the MOA of Factor X?
Human (Coagadex); IV
When would you use Factor X?
Factor X deficiency/Stuart-Prower Factor Deficiency
What are the ADRs for Factor X?
Infusion site erythema, back pain, infusion site pain
What is the MOA of Vitamin K?
Dependent factors: II, VII, IX, X
What is the MOA of Thrombin?
Bovine plasma, topical, powder
When would you use Thrombin?
To arrest minor bleeding/oozing
What is the MOA of Gelfoam?
Absorbable gelatin; senatured collagen, sponge/powder, nonantigenic
When would you use Gelfoam?
Surgery
When would you use von willebrand factor?
Von Willebrand Disease
