Thrombolytics Flashcards
How does plasmin circulate
in inactive form
inactivated by a2 antiplasmin
tPA is a ____ that cleaves ______ to activate plasmin
serine protease
arg-val bond
tPA is inhibited by
PAI-1 & PAI-2
___ forms activator complex with plasminogen
streptokinase
These catalyze conversion of plasminogen to plasmin
Alteplase, Reteplase, Urokinase
_____ inhibits plasminogen –> plasmin
aminocaproic acid
(derivative and analog of lysine)
Indications for thrombolytic therapy
AMI (asap)
Acute Ischemic Thrombotic stroke (within three hours)
PE
tPA’s
- Alteplase
- Reteplase (more potent, faster onset, NO FIBRIN SPECIFICITY b/c lacks binding domain
- Tenecteplase (more fibrin specific than tPA, long half life)
Tenecteplase has point mutations in these domains.
Function of mutations?
Kringle, Protease
- Increase T1/2
- reduce inhibition by PAI
- enhance activity at thrombus
These lack fibrin specificity
Reteplase, Streptokinase
tPA DOA, Clearance, AE’s
5-10 min
Liver & Kidney
Bleeding (internal or superficial)
Streptokinase forms __________
1:1 complex with plasminogen
to produce an active enzyme complex that catalyzes (plasminogen –> plasmin)
Urokinase Dosing, indications, AE’s
IV dose with 15-20 min half life
Massive PE
Bleeding and Allergic rxn (rare)
Anti-fibrinolytic agents used to…
to stop bleeding caused by thrombolytic drugs
Plasmin binds to fibrin through LYSINE site to activate fibrinolysis…. need drugs that act as lysine analogs
Aminocaproic acid, Tranexamic acid (10x more potent)
Clinical indications and AE’s for anti-fibrinolytics
Bleeding associated with thrombolytic therapy, adjunct therapy in hemophelia, rebleeding from intracranial aneurysms
Intravascular thrombosis (not easily lysed!)