Term
|
Definition
| process that maintains the integrity of the circulatory system after vascular damage |
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Term
|
Definition
| adhere to damages endothelium to form platelet plug |
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Term
|
Definition
|
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Term
|
Definition
| clots form upon the conversion of fibrinogen to fibrin & adds to the platelet plug |
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Term
|
Definition
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Term
def
thrombolysis/fibrinolysis |
|
Definition
| process of fibrin digestion by plasmin |
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Term
|
Definition
|
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Term
| What is converted to plasmin? |
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Definition
|
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Term
| What do endothelial cells synthesize & secrete in response to injury to convert plasminogen to plasmin? |
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Definition
| t-PA (tissue plasminogen activator) |
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Term
|
Definition
| cleave fibrin & dissolve clot |
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Term
| What are the 3 major classes of anticoagulant drugs (blood thinners)? |
|
Definition
1) Indirect Thrombin Inbitors
2) Parenteral direct Thrombin Inhibitors
3) Oral Anticoagulants |
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Term
MOA
Indirect Thrombin Inhibitors |
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Definition
| interaction with separate proteins AT III (antithrombin III) & Xa |
|
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Term
| What 2 drugs are indirect thrombin inhS? |
|
Definition
1) heparin
a) LMW
b) HMW
2) fondaparinux |
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Term
|
Definition
| heterogeneous mixture of sulfated mucopolysaccharides |
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Term
|
Definition
| degrade thrombin & factor X when bound to heparin |
|
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Term
| What are the 3 targets of heparin? |
|
Definition
1) IXa
2) Xa
3) IIa (thrombin) |
|
|
Term
| How is heparin used clinically? |
|
Definition
1) venous thrombosis
2) pulmonary embolism
3) acute MI
4) during cardiopulmonary bypass in surgery
5) unstable angina |
|
|
Term
| Why is heparin used for venous thrombosis, pulmonary embolism & acute MI? |
|
Definition
|
|
Term
| What is the clinical application of fondaparinux? |
|
Definition
| thromboprophylaxis of patients undergoing hip/knee durgery (to prevent pulmonary embolism & deep vein thrombosis) |
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Term
| How is heparin therapy monitored? |
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Definition
| by aPTT (activated partial thromboplastin time) |
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Term
|
Definition
1) bleeding
2) heparin induced thrombocytopenia |
|
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Term
| What are the 3 parenteral direct thrombin inhibitors? |
|
Definition
1) Hirudin
2) Bivalrudin
3) Aragatroban |
|
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Term
| Which of the parenteral direct thrombin inhibitors is irreversible? |
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Definition
|
|
Term
| What is the target of the parenteral direct thrombin inhibitors? |
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Definition
|
|
Term
| When is hirudin used clinically? |
|
Definition
| heparin-induced thrombocytopenia |
|
|
Term
| What must be monitored while a patient is on hirudin? |
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Definition
|
|
Term
| What is bivalirudin used for clinically? |
|
Definition
| alternative to heparin in patients undergoing coronary angioplasty |
|
|
Term
| What is aragatroban used for clinically? |
|
Definition
| alternative to hirudin for prophylaxis/Tx of patients with or at risk of developing haparin0induced throbmocytopenia |
|
|
Term
| When should parenteral direct thrombin inhibitor use be closely monitored? |
|
Definition
| renal failure => can accumulate and cause bleeding |
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|
Term
Sx
parenteral direct thrombin inhibitor toxicity |
|
Definition
| antihirudin Ab => paradoxical increase in aPTT (i.e. must monitor aPTT daily) |
|
|
Term
| What are the 2 oral anticoagulants (oral direct thrombin inhibitors)? |
|
Definition
1) Warfarin
2) Next generation |
|
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Term
|
Definition
| synthetic derivative of coumarin (found in plants) |
|
|
Term
| What is the bioavailability & half life of warfarin? |
|
Definition
BioA: 100%
Half life: 36 hr (long) |
|
|
Term
| How does warfarin compare to heparin? |
|
Definition
|
|
Term
|
Definition
| inhibits Vit K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors & a regulatory factor => no clot formation |
|
|
Term
| What are the calcium-dependent clotting factors? |
|
Definition
|
|
Term
| What regulatory protein does warfarin inhibit synthesis of? |
|
Definition
|
|
Term
|
Definition
| block γ-carboxylation of glutamate residues in coagulation factors => incomplete coagulation factor molecules biologically inactive |
|
|
Term
| What are the 4 targets of warfarin? |
|
Definition
VII
IX
X
Prothrombin II
Protein C |
|
|
Term
| How is warfarin used clinically? |
|
Definition
1) prevent progression/recurrence of acute deep vein thrombosis/pulmonary embolism following initial heparin course
2) prevent venous thromboembolism in patients undergoing ortho/gyn surgery
3) prevents systemic embolization in patients with acute MI, prosthetic heart valves, or chronic atrial fibrillation |
|
|
Term
| In what patients should warfarin never be used? |
|
Definition
|
|
Term
| When should warfarin be used with caution? |
|
Definition
congenital coagulation factor deficiency
thrombocytopenia
hepatic/renal insufficiency |
|
|
Term
| What defines the therapeutic range for oral anticoagulant therapy? |
|
Definition
| international normalized ratio (INR) |
|
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Term
|
Definition
| patients PT(prothrombin time)/mean of normal PT for lab |
|
|
Term
|
Definition
| progression/recurrance of a thrombotic effect |
|
|
Term
| When are patients more likely to form warfarin resistance? |
|
Definition
|
|
Term
| What does increasing the INR increase the risk of? |
|
Definition
|
|
Term
| What 2 drugs is warfarin anticoagulation effect decreased? |
|
Definition
|
|
Term
| What 2 drugs is warfarin anticoagulation effect augmented? |
|
Definition
|
|
Term
| What are the 3 next generation oral anticoagulants? |
|
Definition
1) Pradaxa
2) Rivaroxiban
3) Apixaban |
|
|
Term
| What are the targets of the next generation oral anticoagulants? |
|
Definition
Rivaroxaban & Apixaban: Xa
Pradaxa: IIa (thrombin) |
|
|
Term
| What are the 2 advantages of apixaban? |
|
Definition
reduce risk of :
1)stroke in patients with atrial fibrillation (a-fib)
2)major bleeding |
|
|
Term
| What are the 2 advantages of pradaxa? |
|
Definition
reduce risk of:
1) stroke & 2) systemic embolism in patients with a-fib |
|
|
Term
| What are the 2 advantages of rivaroxaban? |
|
Definition
reduce risk of:
1) intracranial & 2) fatal bleeding |
|
|
Term
| What are the 2 advantages of all next generation oral anticoagulants over warfarin? |
|
Definition
1)no monitoring needed
2)less DDI |
|
|
Term
| What 2 next generation oral anticoagulants lower stroke risk in a-fib? |
|
Definition
|
|
Term
| What 2 next generation oral anticoagulants reduce risk of bleeding? |
|
Definition
|
|
Term
| Do any of the oral anticoagulants have a antidote? |
|
Definition
|
|
Term
Function
fibrinolytic drugs |
|
Definition
| rapid lysis of thrombi by catalyzing activation of plasmin |
|
|
Term
def
t-PA (tissue plasminogen activator) |
|
Definition
| endogenous serine protease that is a poor plasminogen activator in the absence of fibrin |
|
|
Term
| How does t-PA activate plasminogen? |
|
Definition
| binds fibrin via lysine binding sites at amino terminus => activation of plasminogen |
|
|
Term
| What controls t-PA clearance? |
|
Definition
|
|
Term
| What is the half life of t-PA? |
|
Definition
|
|
Term
| What produces streptokinase? |
|
Definition
|
|
Term
|
Definition
| cofactor for the cleavage plasminogen to form free plasmin |
|
|
Term
| How does streptokinase induce cleavage of plasminogen to plasmin? |
|
Definition
| form stable complex with plasminogen to expose active site |
|
|
Term
| When is t-PA used clinically? |
|
Definition
1) lysing thrombi during Tx of acute MI
2) pulmonary embolism
3) severe deep vein thrombosis |
|
|
Term
| How do recominant mutant varients of t-PA differ from native t-PA? |
|
Definition
|
|
Term
Sx
Fibrinolytic drug toxicity |
|
Definition
|
|
Term
| What are the 2 possible causes of hemorrhage in fibrinolytic drugs? |
|
Definition
1) lysis of fibrin in physiological thromi at sites of vascular injury
2) systemic lytic state that results from systemic formation of plasmin => fibrinogenolysis & destruction of other coagulation factors (esp. V & VIII) |
|
|
Term
| What is the antidote to fibrinolysic drug toxicity to inhibit fibrinolysis? |
|
Definition
|
|
Term
| What are the 7 contraindications of thrombolytic therapy? |
|
Definition
1) surgery within 10 days
2) serious GI bleed within 3 mo
3) Hx of HTN
4) Active bleeding/hemorrhagic disorder
5) Previous cerebrovascular accident or active intracranial process
6) Aortic dissection
7) Acute pericaditis |
|
|
Term
| What are the 5 antiplatelet drugs? |
|
Definition
1) aspirin
2) dipyridamole
3) clopidogrel
4) ticlopidine
5) glycoprotein IIb/IIIa inhibitors |
|
|
Term
|
Definition
| block platelet aggregation & vasoconstriction |
|
|
Term
|
Definition
| inhibit synthesis of TXA2 (thromboxane A2) via acetylation of serine residue near active site of COX-1 |
|
|
Term
Function
COX-1 (cyclooxygenase) |
|
Definition
| produce cycliv endoperoxide precursor of TXA2 |
|
|
Term
|
Definition
1) vasodilator
2) inhibits embolization from prosthetic heart vavles, strokes, transient ischemic attack |
|
|
Term
|
Definition
| inhibit platelet activation |
|
|
Term
MOA
clopidogrel & ticlopidone |
|
Definition
| platelet ADP receptor antagonist |
|
|
Term
| What are the 3 glycoprotein IIb/IIIa inhibitors? |
|
Definition
1) Abciximab
2) Eptifibatide
3) Tirofiban |
|
|
Term
MOA
glycoprotein IIb/IIIa inhibitors |
|
Definition
| block binding of glycoprotein IIb/IIIa platelet-surface integrin to fibrinogen => inhibition of platelet aggregation |
|
|
Term
|
Definition
| Fab portion of Ab to Glycoprotein IIb/IIIa platelet-surface integrin |
|
|
Term
|
Definition
| cyclic peptide inhibitor of fibrinogen binding site on Glycoprotein IIb/IIIa platelet-surface integrin |
|
|
Term
|
Definition
| nonpeptide, small-molecule inhibitor of Glycoprotein IIb/IIIa platelet-surface integrin |
|
|
Term
| When is aspirin used clinically? |
|
Definition
1) immediately after one MI to reduce risk of second or death of cardiac tissue
2) long-term prevention of MI, strokes, & blood clot formation in high risk ppl |
|
|
Term
| When is dipyridamole used clinically? |
|
Definition
| in combination of warfarin for post-op primary prophylaxis of thromboemboli in patients with prosthetic heart valves |
|
|
Term
| When is ticlopidine used clinically? |
|
Definition
| reduce risk of thrombotic stroke in patients who have experienced stroke precursors or have had a thrombotic stroke |
|
|
Term
| When is clopidogrel used clinically? |
|
Definition
1)with aspirin after angioplasty (1 yr)
2)to reduce risk of stroke & MI in patients with recent MI or stroke, established peripheral aterial disease, or acute coronary syndrome |
|
|
Term
|
Definition
|
|
Term
| What 2 drugs when combined with aspirin can increase the risk of upper GI bleeds? |
|
Definition
|
|
Term
|
Definition
Common: N/V/D
most serious: leukopenia |
|
|
Term
| What antiplatelet drug has the most favorable toxicity profile? |
|
Definition
|
|
Term
| Why does clopidogrel have the most favorable toxicity profile than any other antiplatelet drugs? |
|
Definition
| less frequent thrombocytopenia & leukopenia |
|
|
Term
| When is abciximab used clinically? |
|
Definition
in conjunction with:
1)percutaneous angioplasty for coronary thrombosis
2)aspirin & heparin to prevent resenosis, recurrent MI & death |
|
|
Term
| What is eptifibatide used for clinically? |
|
Definition
1)acute coronary syndrome
2)angioplastic coronary interventions => reduced MI & death |
|
|
Term
| What is tirofiban used for clinically? |
|
Definition
in conjunction with heparin for:
1) non-Q wave MI
2) unstable angina |
|
|
Term
SE
abciximab & eptifibatatide |
|
Definition
|
|
Term
| What can reverse the aggregation defect induced by abciximab or eptifibatide? |
|
Definition
|
|
Term
|
Definition
| bleeding on local sites of clinical inervention & systemically |
|
|
Term
| How do you reverse the effects of tirofiban? |
|
Definition
| tranfusions (to terminate bleeding & improve bleeding-related anemia) |
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