Fibrinolytic Drug Flashcards
Clot Dissolution
when the blood vessel defect has healed, the ___ pathway is activated to dissolve the clot
fibrinolytic
General Mechanism of Thrombolytic drugs
all thrombolytics work to increase the conversion of ___ to ___
- ___ in turn degrades ___ and dissolves a clot
- plasminogen, plasmin
- plasmin, fibrin
Fibrinolytic Pathway
- ___ , an anticoagulant protein circulated in inactive form and is deposited on to growing clot
- tissue plasminogen activator (t-PA), a ___ protease, can activate plasminogen to plasmin
- plasmin is a proteolytic enzyme that digests ___ and ___
- t-PA is inhibited by ___ and ___
- t-PA cleaves ___ - ___ bond to activate plasmin
- plasmin is inactivated by ___
- plasminogen
- serine
- fibrin, fibrinogen
- PAI-1, PAI-2
- arg-val
- a2-antiplasmin
Indications for Thrombolytic Therapy
- acute ___ - initiate as soon as possible after onset of ___
- acute ischemic thrombotic ___ - initiate only within 3 hrs after onset and exclusion of ___ hemorrhage
- ___ embolism
- myocardial infarction, AMI
- stroke, intracranial
- pulmonary
Acute Myocardial Infarct
Standard of Care-Stent Placement
- bare-metal stents vs drug-coated stents
- drugs prevent ___ by inhibiting smooth muscle cell ___ , but increase risk of subsequent thrombosis
- restenosis
- proliferation
Thrombolytic Drugs - Tissue Plasminogen Activator (t-PA)
binds to ___ and activates bound ___ 100x more rapidly than in circulation
alteplase (Activase)
- recombinant human t-PA - 527 aa residues
- binds ___
reteplase (Retevase)
- recombinant human t-PA with ___ of aa (355/527)
- more ___, faster onset
- lacks fibrin binding domin - less fibrin- ___
tenecteplase (TNKase)
- recombinant, ___ form of t-PA
- ___ t1/2, given by single IV bolus
- more fibrin ___ than t-PA
- fibrin
- plasminogen
- fibrin
- deletion
- potent
- specific
- mutant
- longer
- specific
t-PA structure
mutations in Tenecteplase
- ___ half-life
- reduce inhibition by ___
- enhance activity at ___
- longer
- PAI
- thrombi
t-PA
tissue plasminogen activator (t-PA)
- plasminogen bound to fibrin is selectively activated by ___ that is also bound to fibrin
t-PA
tissue plasminogen activator
- ___ administration only
- ___ duration of action
- t 1/2 = ___ - ___ min (Alteplase), __ - ___ min (Reteplase), ___ - ___ min (Tenecteplase)
- clearance primarily by ___ and ___
adverse effects
- ___ is most common complication
- ___ bleeding
- superficial or surface bleeding
- IV
- short
- 5-10, 13-16, 90-130
- liver, kidney
- bleeding
- internal
Anti-fibrinolytic agents
used to stop bleeding caused by ___ drugs
- plasmin binds to fibrin through a ___ binding site to activate fibrinolysis
- drugs act as a lysine analog to bind the receptor on plasminogen and plasmin
- the result is blockade of ___ binding to target ___
- ___ acid is 10x more potent than ___ acid
- thrombolytic
- lysine
- plasmin, fibrin
- tranexamic, aminocaproic
Anti-fibrinolytic agents
Clinical Uses:
- treat bleeding associated with ___ therapy
- adjunct therapy in ___
- re-bleeding from ___ aneurysms
Major risks
- intravascular thrombosis as result of ___ inhibition
- thrombi formed during therapy are not easily ___
- thrombolytic
- hemophilia
- intracranial
- fibrinolysis
- lysed
Anti-fibrinolytic agents
tranexamic acid and aminocaproic acid prevent binding of ___ and ___ to fibrin, sparing clots and preventing hemorrhage
plasminogen, plasmin
