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41 Cards in this Set
- Front
- Back
Events of hemostasis
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1. vasospasm
2. platelet plug formation (primary hemostasis) 3. blood coagulation (secondary hemostasis) 4. dissolution of the fibrin clot (tertiary hemostasis) |
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Platelet secretions
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ADP, Ca, ATP, serotonin, vWF, platelet factor 4, TXA2
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Anticoagulant factors
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PGI2, antithrombin III, Proteins C and S, Tissue Factor pathway inhibitor (TFPI), tissue plasminogen activator (t-PA)
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Aspirin
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Platelet aggregation inhibitor
irreversible inhibition of COX enzymes (acetylation) therefore no TXA2, prolongs bleeding time. Use: reduce incidence of MI, decrease mortality in MI pts. |
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Clopidogrel, Triclopidine
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ADP receptor Blockers
irreversibly bind to P2Y12- no platelet activation U: prevent thrombosis in stent pts. Ad: thromcytopenic purpura inhibit cytochrome P450 Triclopidine- neutropenia Clopidogrel preferred b/c of side effects |
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Dipyridamole
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Phosphodiesterase Inhibitor
increases CAMP levels by inhibiting phosphodiesterase and/or blocking uptake of adenosine - no platelet activation U: coronary vasodilator +warfarin= prophyaxis of thromboemboli in prosthetic ht. valve pts. +aspirin= prophylaxis of cerebrovascular disease |
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Cilostazol
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Phosphodiesterase inhibitor
vasodilation, inhibition of platelet aggregation U: tx of intermittent claudication |
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if No GP IIb, IIIa receptor
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Glanzmann's thrombathenia
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Abciximab
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GP IIb, IIIa blocker
irreversible t1/2= 18-24 hrs. parenteral |
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Eptifibatide
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GP IIb, IIIa blocker
reversible peptide parenteral |
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Tirofiban
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GP IIb, IIIa blocker
reversible nonpeptide tyrosine analog parenteral |
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Types of Anticoagulants
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1.unfractioned heparin, low molecular weight heparin
2. selective factor Xa inhibitors 3.direct thrombin inhibitors 4. coumarin anticoags. |
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heparin mechanism
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binds to antithrombin III and causes rapid activity to inhibit:
1. thrombin 2. factor IXa 3. factor Xa sequence of 5 carbohydrate residues is essential for heparin binding accelerates rxn 1000x |
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low molecular weight heparin
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inhibit activated factor X, less activity on thrombin
equal efficacy as unfractioned heparin, increased bioavail., and less freq. dosing ex.= enoxaparin, dalteparin, tinzaparin |
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Monitoring heparin levels
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use activated partial thomboplastin time(aPTT)- measures intrinsic pathway
-only for unfractioned heparin -low mol wt. heparin has high therapeutic index therefore not necessary to monitor levels -->use specialized assay for anti-factor Xa |
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heparin uses
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prevent fibrin formation
prevention of venous thrombosis |
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heparin adverse effects
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1. bleeding
2. hypersensitivity 3. heparin induced thrombocytopenia |
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heparin induced thrombocytopenia
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2 types- I=mild small decrease in platelet number
II= systemic hypercoagulable state caused by Ab's that recognize heparin and Platelet Factor 4 -IgG binds to Fc receptor which causes platelet degranulation and aggregation. --> thrombocytopenia via platelet comsumption if HIT, discontinue heparin, administer direct thrombin inhibitor or fondaparinux |
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reversal of heparin administration
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discontinue drug
if bleeding, use protamine sulfate -protamine does not reverse effect of fondaparinux |
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Danaparoid
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low molecular weight heparin
contains heparan sulfate, dermatan sulfate, chondroiton sulfate - DEVOID of heparin or heparin fragments U: prophylaxis of deep vein thrombosis, Tx of HIT |
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Fondaparinux
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Factor Xa inhibitor
binds to antithrombin III and induces conformation change req. for binding to factor Xa U: prevention and Tx of deep vein thrombosis subcutaneous injection |
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Lepirudin
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Direct thrombin inhibitor
-binds directly to active site of thrombin can inactivate both free and fibrin-bound thrombin since it is independent of antithrombin III activity parenteral monitor with aPTT U: thrombosis related to HIT AD: renal problems, no antidote exists |
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Desirudin
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direct thombin inhibitor
U: prophylaxis against deep vein thrombosis monitor with aPTT |
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Bivalirudin
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direct thombin inhibitor
also inhibits platelet activation aPPT U:percutaneous coronary angioplasty |
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Argatroban
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direct thombin inhibitor
small molecule thombin inhibitor IV U: HIT monitor with aPTT |
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Coumarin Anticoagulants
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warfarin, dicumarol
ORAL antagonize cofactor function of vitamin K |
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coumarin mechanism
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inhibit vitamin K epoxide reductase
- inhibits factors II, VII, IX, X effects on seen for 8-12 hrs. can be reversed by administration of Vit. K - takes 24 hrs |
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Warfarin
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Coumarin Anticoagulant
narrow therapeutic index monitored by prothombin time (PT) - extrinsic pathway AD: 1. bleeding- if minor, withdraw drug and oral vit. K. if major, IV vit. K 2. Cutaneous necrosis.- reduced activity of Protein C. Pro. C is dependent on vit K also. 3.Crosses placenta- abnormal bone formation 4. many drug interactions |
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Drug interactions of Warfarin
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Inhibit warfarin metabolism (potentiation):
cimetidine, chloramphenicol, disulfiram, fluconazole, mentronidazole, phenylbutazone, sulfinpyrazone, trimethoprim-sulfamethoxazole Drugs stimulating warfarin metabolism: barbiturates, carbamazepine, phenytoin, rifampin |
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Thrombolytics
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Used to lyse formed clots and restore patency of vessel.
convert plasminogen to plasmin U: unclotting catheters, unclotting shunts, strokes, in MI if angioplasty not available AD: 1.bleeding 2. contradicted in healing wounds, pregnancy, history of cerebrovascular problems or metasaic cancer |
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Streptokinase
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Thrombolytic
combines with plasminogen - converts to plasmin - degrades fibrinogen and factors V, VII |
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Urokinase
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thrombolytic
converts plasminogen to plasmin U: plumonary emboli |
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Alteplase, Reteplase, Tenecteplase
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tissue plasminogen activator
- fibrin selective - during therapeutic infusion of t-PA, higher concentrations of t-PA leads to higher concentrations of plasminogen alteplase: t1/2= 3-6 min - tx of acute MI, acute massive pulm. embolism, acute ischemic stroke Reteplase: t1/2= 14-18min -given in double bolus -management in acute MI - less fibrin specific than t-PA Tenecteplase: t1/2= 20-24 min -single IV bolus - used to reduce mortality in acute MI -more fibrin specific than t-PA |
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Anistreplase
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complex of human plasminogen and bacterial streptokinase
DISCONTINUED IN USA |
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Venous Thrombosis
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Prevention:
low dose of UF heparin, LMW heparin, or fondaparinux also warfarin but needs to be monitored Tx: UF or LMW heparin for first 5-7 days with overlap of warfarin. continue warfarin for 3-6 mo. if in pregnant woman- just heparin |
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Arterial thrombosis
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aspirin and clopidogrel or triclopidine
- TIA, strokes, unstable angina and acute MI if angina and MI, combo with beta blockers, calcium channel blockers, and fibrinolytic drugs |
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aminocaproic acid, tranexamic acid
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inhibit plasminogen activation, therefore no plasmin
U: therapy in hemophilia, bleeding from fibrinolytics AD: thrombosis, hypotension |
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Protamine sulfate
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chemical antagonist of heparin
-forms inactive complex with heparin IV most active on UF heparins -inactive against fondaparinux AD: hypersensitivity, dyspnea, flushing, bradycardia, hypotension |
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Vitamin K
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stops bleeding due to oral anticoagulants (warfarin)
complete effect at 24 hrs. but starts after 6 hrs. |
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Aprotinin
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Serine protease inhibitor
-blocks plasmin, plasmin-streptokinase complex U: blood loss in bypass surgery WITHDRAWN IN 2007 |
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Hemophilia A
Hemophilia B |
A= def of factor VIII
B= def of factor IX |