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91 Cards in this Set
- Front
- Back
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receptor on platelets that binds fibrinogen and other macromolecules?
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GP IIb/IIIa
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prostacyclin?
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antiplatelet factor released from endothelium
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aggregating substances released from degranulating platelet?
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ADP
TXA2 5HT |
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what is drotrecogin alpha and how is it used clinically?
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activated protein C
to treat septic shock |
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UFH (unfractionated heparin)?
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glycosaminoglycan from animal source
high density of (-) charges 1/3 have necessary sequence for activity |
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necessary part of heparain for activity?
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pentasaccharide sequence
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LMWH (low molecular weight heparins)?
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digest unfractionated heparin
only 15-25% contain necessary sequence |
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fondaparinux?
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synthetic pentasaccharide binding sequence for heparin
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actions of heparins?
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effective anticoagulant in vivo and in vitro;
arrests thrombosis and prevents embolization especially on the venous side of circulation; prolonged whole blood clotting time, thrombin time, prothrombin time, partial thromboplatin time; bleeding times may be unaltered |
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heparin mechanism?
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antithrombin catalyst to inhibit proteolytic activity of most of the proteolytic enzymes (IIa and Xa are most important);
enhance activity of the Tissue Factor Pathway Inhibitor |
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most important enzymes inhibited by heparin?
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IIa
Xa |
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which enzyme are LMWH and fondaparinux unable inhibit and why?
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IIa;
complex can formed only by chains at least 18 saccharides long; so these are more Xa selective |
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major disadvantage of heparins?
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must be administered parenterally
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which route of administration is avoided with heparins and why?
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IM, possible hematoma
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UFH elimination?
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half life is dose dependent and nonlinear due to rapid but saturable mechanism and slower, non-saturable, dose-independent renal clearance
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LMWH and fondaparinux elimination?
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by renal clearance;
more predictable anticoagulant response with better bioavailability, longer half-life, and dose-independent clearance |
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enoxaparin?
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LMWH
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dalteparin?
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LMWH
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tinzaparin?
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LMWH
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toxicity associated with heparins?
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major bleeding
osteoporosis |
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major bleeding as toxicity with heparins?
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UFH > LMWH
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osteoporosis as toxicity with heparins?
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seen only on prolonged use of 10-15000 UFH/day for more than one month
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HIT (heparin induced thrombocytopenia)?
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due to IgG against complexes of UFH and platelet factor 4 that form on the surface of platelets and activate their Fc-gamma-RIIa receptors;
platelets count begins to decline 5-10 days after starging UFH; less likely SC; associated with thromboembolic disorders |
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patients at highest risk of HIT?
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postoperative orthopedic
cardiac surgery vascular surgery |
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thromboembolic disorders associated with HIT?
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DVT
DIC pulmonary embolism cerebral thrombosis MI ischemic injury to legs or arms |
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lepirudin?
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recombinant derivative of hirudin
direct irreversible thrombin inhibitor approved for patients with HIT heparin substitute no antidote |
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argatroban?
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direct reversible thrombin inhibitor
approved for patients with HIT heparin substitute no antidote |
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why do lepirudin and argatroban make the transition to warfarin complicated?
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can increase INR
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why is warfarin not substituted for UFH in HIT?
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has been associated with venous limb gangrene or multicentric skin necrosis;
should not be used until thrombocytopenia has been resolved |
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treatment of heparin overdose?
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withdrawal of UFH
protamine |
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protamine?
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basic protein that combines with UFH to form a stable salt;
can only neutralized anti-IIa activity of LMWH; does not reverse fondaparinux |
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most common test for UFH effect?
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activated partial thromboplastin time (aPTT)
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most accurate and reliable test for UFH effect?
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factor Xa titration
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coumarins action?
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suppress formation, by the liver, of some of the factors involved in blood coagulation
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coumarins mechanism?
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antagonize action of vitamin K;
block generation of gamma-carboxyglutamic acid residues; required for factors II, VII, IX, X and proteins C and S |
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major disadvantage of coumarins?
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long latent period - must wait for clotting factors to be catabolized or resynthesized at conclusion of therapy
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which isomer of warfarin is most potent and how is it metabolized?
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S-warfarin
CYP2C9 |
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less potent warfarin isomer and how is it metabolized?
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R-warfarin CYP1A2
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major advantage of warfarin?
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can be given orally
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challenges of warfarin therapy?
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narrow therapeutic window;
variability in dose response; interactions with drugs and diet; lab control is difficult to standardize; understanding of pharmacokinetics and pharmacodynamics; need good patient communication |
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factors involved in patient's response to warfarin?
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vitamin K
liver disease congestive heart failure (hepatic congestion) presence of infection following surgery hypermetabolism presence of other drugs/herbals |
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what factors increase patient's sensitivity to warfarin?
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infection
postoperative hypermetabolism |
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genetic variations that have consequence to warfarin therapy?
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CYP2C9 and VKORC1
may need to lower warfarin doses in these individuals |
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which drugs potentiate warfarin's effects?
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fluconazole
amiodarone omeprazone |
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fluconazole + warfarin interaction?
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inhibition of CYP2C9
increased S-warfarin |
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amiodarone + warfarin interaction?
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increased S and R warfarin
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omeprazole + warfarin interaction?
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increased R-warfarin
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drugs that inhibit actions of warfarin?
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cholestyramine
barbiturates vitamin K |
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cholestyramine + warfarin interaction?
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binding in gut to decrease absorption
decreased plasma levels |
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barbiturates + warfarin interaction?
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increased metabolism due to induction of CYP;
decreased warfarin plasma levels |
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vitamin K + warfarin interaction?
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decreased effect of warfarin
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toxicity associated with warfarin?
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bleeding
recurrent skin necrosis |
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most consistent risk factor for bleeding with warfarin therapy?
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history of bleeding (especially GI)
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warfarin and pregnancy?
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warfarin can cross the placenta so should be avoided
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when should patients wear a 'medic alert' bracelet?
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if on anticoagulant
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treatment of warfarin overdose?
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prothrombin complex concentrates
oral vit K (phytonadione) |
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phytonadione?
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oral vit K
may complicate reestablishment of warfarin therapy since has long duration of action |
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recommendations on antithrombic and thrombolytic therapy?
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heparins are used immediately (rapid onset);
warfarin administered at same time as heparin; heparin is not discontinued until INR indicates that warfarin is effective |
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purpose of INR?
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absolute prothrombin time can vary and this allows a way for it to be standardized
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for which condition is recommended range of INR higher than the usual 2-3?
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2.5-3.5 for mechanical prosthetic heart valves
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streptokinase?
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binds to plasminogen thereby converting plasminogen into a plasmin like molecule capable of converting plasminogen to plasmin
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alteplase?
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tPA
requires fibrin for activity - less random proteolytic dstruction of blood clotting factors |
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reteplase?
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nonglycosylated deletion mutation of wild type tPA
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tenecteplase?
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derivative of alteplase
advantage of single bolus administration |
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which fibrinolytics have specificity for fibrin?
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alteplase
reteplase tenecteplase |
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which fibrinolytic is antigenic?
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streptokinase
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which fibrinolytic can be administered as single bolus?
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tenecteplase
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therapeutic use of fibrinolytics?
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treat acute MI as an alternative to PCI
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importance of time in administering fibrinolytics?
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recently formed thrombi are easier to lyse than aged thrombi
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which fibrinolytic is approved for acute ischemic stroke?
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alteplase
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adverse effects of fibrinolytics?
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bleeding
arrhythmias (on reperfusion) fever and allergic reactions (streptokinase) |
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aminocaproic acid?
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binds reversibly to plasminogen to block binding of plasminogen to fibrin and its activation and transformation to plasmin
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novoseven?
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rFVIIa
treatment of bleeding episodes in hemophilia patients with inhibitors to factor VIII or IX; off label to stop other instances of uncontrolled bleeding |
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why low doses of aspirin?
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COX1 in platelets are inhibited more selectively because lower doses are required;
higher doses would inhibit formation of prostacyclin that is actually an antiplatelet agent |
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vascular disorders for which aspirin has been shown to be effective and lowest effective dose?
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TIA and ischemic stroke (50 mg)
unstable angina (75 mg) acute MI (160 mg) acute ischemic stroke (160 mg) |
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clopidogrel?
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irreversible blocking of P2Y12 purinergic receptor for adenosine diphosphate which indirectly inhibits the binding of fibrinogen to its platelet receptor (GIIb/IIIa)
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prasugrel?
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irreversible blocking of P2Y12 purinergic receptor for adenosine diphosphate which indirectly inhibits the binding of fibrinogen to its platelet receptor (GIIb/IIIa)
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clopidogrel pharmacokinetics and consequences?
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prodrug converted to active form by two CYP-dependent oxidation steps;
function polymorphisms may interfere in as many as 30% of patients |
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prasugrel pharmacokinetics?
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prodrug that undergoes hydrolysis by intestinal esterases and only one CYP-dependent oxidation step to convert to active form
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indications for clopidogrel and prasugrel?
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prophylaxis before and after PCI in combination with aspirin;
acute coronary syndrome; post MI porpylaxis; stroke prevention in TIA or previous thrombotic stroke |
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PCI?
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percutaneous coronary intervention
(ie angioplasty) |
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adverse effects of ADP pathway inhibitors?
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bleeding (prasugrel > clopidogrel)
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clopidogrel interactions?
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CYP2C19 inhibitors (proton pump inhibitors: omeprazole, esomeprazole);
caution with other drugs that may cause bleeding |
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abciximab?
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Fab fragment of monoclonal antibody
GIIb/IIIa antagonist |
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most efficacious platelet agents?
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GIIb/IIIa antagonists
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eptifibatide?
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GIIb/IIIa antagonist
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tirofiban?
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GIIb/IIIa antagonist
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GIIb/IIIa antagonists administration?
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IV in the hospital
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bivalirudin?
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direct reversible thrombin inhibitor (derived from hirudin);
inactivates platelet bound Xa and clot bound thrombin; no known antidote |
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indications for bivalirudin?
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used (with aspirine, clopidogrel and provisional GPI) instead of heparin in patients with unstable angina undergoing PCI
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dipyridamole?
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inhibition of phosphodiesterase
blockade of uptake of adenosin combo with low dose aspirin for stoke prevention |
