Module 2 exam 1 lecture 4 Flashcards
how is the clot dissolved once BV is healed
fibrinolytic pathway
major step of fibrinolytic pathway
activation of plasminogen to plasmin
What is plasminogen
a circulating inactive enzyme
plasminogen is activated by
TPA (tissue plasminogen activator)
What does plasmin do?
binds to plasmin clot and breaks it down
indication of thrombolytic drugs
dissolve clots, acute MI, stroke
What does TPA do?
BInds fibrin and activates plasminogen that is bound to fibrin clot. Breaks down 100X more rapidly
3 drugs that dissolve blood clots (TPAs)
Alteplase
reteplase
tenecteplase
alteplase structure and MOA`
recombinant human TPA
binds fibrin
Reteplase structure and MOA
shorter (truncated, removed aa from protease domain) no fibrin binding domain, less fibrin specific.
TEnecteplase structure and MOA
Point mutation in protease domain that increases ability to bind fibrin. longer t1/2
summarize how a clot is broken down
Plasminogen binds to fibrin clot, T-PA (altepase or tenecteplase) will bind to clor and plasminogen and activate it to plasmin
Which TPA is different in terms of function? why?
Reteplase. It has no fibrin binding domain so it cleaves plasminogen whether it is bound to the clot or not
How are TPA drugs cleared
renally and hepatically
ROA for alteplase, reteplase, tenecteplase? t1/2?
IV for all
alteplase- 5-10 min
reteplase- 13-16 min
tenecteplase- 90-130 min
Adverse effects of TPAs
Bleeding
How do we stop bleeding caused by TPAs?
Antifibrinolyctic agents
Name antifibrinolytic drugs
Aminocaproic acid (EACA)
Tranexamic acid
Which aa are aminocaproic acid and tranexamic acid based on?
Lysine
Which antifibrinolytic drug is more potent
Tranexamic acid is 10x more potent than aminocaproic acid
How do tranexamic acid and aminocaproic acid work?
Prevent binding of plasminogen and plasmin to fibrin, sparing clots and preventing hemorrhage.
inhibitors of platelet function are normally given iin PCI, why?
PCI is catheterization through BV. This will cause endothelial damage and induce platelet aggregation. Inhibitors of platelet function stop this.
What does heparin inhibit
antithrombin 3
MOA of heparin
accelerates binding of antithrombin 3 to thrombin (factor 2a) and factor Xa
What does thrombin do when activated?
cleaves fibrinogen to fibrin
heparin inhibits conversion of
prothrombin to thrombin and fibrinogen to fibrin
LMWH drugs
Enoxaparin
Palteparin
LMWH MOA difference from heparin MOA
Inactivate Xa, but has little inactivation at thrombin due to short chains
time required to get peak anticoag effect from warfarin
2-3 days
warfarin MOA
Warfarin inhibits gamma-carboxylated factors (II,VII, IX and X). They must be depleted
Which compound targets the binding of platelets to fibrinogen
eptifibatide (prevents crosslinking of platelets)
Name an antibody that binds to GPIIb/IIIa receptors
Abciximab
Protease activated receptor (PAR) is cleaved by what molecule in coagulation cascade
factor IIa (thrombin)
protein C and S are dependent of which vitamin?
K
What might cause deficiency in prothrombin (factor II) or in factor x
liver disease or vit K
