Thrombolytics + extra (STEMI/NSTEMI/UA) Flashcards
Thrombolytics
Alteplase
Reteplase
Tenecteplase
Thrombolytics Indications
PCI within 90 minutes door to balloon time
Lytics within 30 minutes if PCI within 90 minutes is impossible-door to needle time
Hemodynamically compromised pts (cardiogenic shock, pulm edema, congestion) receiving lytics to receive angiography and PCI
Thrombolytics MOA
lytics dissolve pathologic thrombus and fibrin at sites of vascular injury:
- endogenous tissue plasminogen activator (t-PA) released from endothelium
- plasminogen converted to plasmin
- plasmin digests clot bound fibrin
Lytics can be used in ____ but not ___ or __
use lytics in STEMI ONLY***!!!!!
DO NOT USE IN UA/NSTEMI
- NOT better when added to ASA, clopidogrel, anticoag, and GP IIB/IIIA inhibitors
- actually will increase risk of MI and other serious hemorrhagic events ☹
Lytics Considerations
New and improved lytics are based on endogenous t-PA
structures make each unique: Finger and Kringle pieces an effect fibrin specificity, potency, clearance etc
alteplase is more like tenecteplase but overall all 3 have same efficacy!
Lytics reversal?
Lytics CAN be reversed with AMINOCAPROIC ACID ☺
- binds to lysine on plasminogen and plasmin
- prevents interaction with fibrin
Alteplase MOA
Serine protease cleaves Arg-Val bond in plasminogen and converts it to plasmin
*Requires fibrin as cofactor for activation of plasminogen
-enhanced proteolysis in presence of clot fibrin, highly specific for clot bound fibrin
No direct antiplatelet effects
Alteplase indication
Given with UFH or enoxaparin
LESS active on systemically circulating plasminogen
Alteplase Metabolism
Non antigenic
- moderate degree of fibrin depletion and D dimmer accumulation
- peak thrombolytic effects within 30-60 minutes, IV infusion required to maintain lysis
75% achieve patency within 90 minutes
>50% achieve TIMI grade 3 flow
Alteplase clearance
Degraded into component amino acids in liver
-50% of alteplase cleared within 5 minutes of stoping infusion, 80% in 10 minutes
half life 27-46 minutes
Alteplase CI/ Precautions
CI: -bleeding -uncontrolled htn***** -av malformation or aneurysm -HX/evidence of hemorrhagic stroke -SAH -Platelets less than 100,000 Heparin w/in 48 hours precautions: recent trauma, high bleed risk, recent punctures
Alteplase considerations
Replaced streptokinase bc of fibrin secificty
Recteplase MOA
Catalyzes conversion of plasminogen to plasmin and enhances thrombolysis
Early platelet inhibition within 6 hrs with rebound platelet aggregation at 24 hrs with increased GP IIb/IIIa expression
Recteplase indications
Given with UFG, enoxaparin
Recteplase Metabolism
Peak response within 30-90 min of IV -60-70% achieve patency by 90 minutes -60% with TIMI grade 3 flow inactivated in blood by: -C1 inactivator -a-1 antitrypsin -a-2 antiplasmin RENAL clearance Half life 13-16 minutes
Recteplase CI/precautions
CI:
- bleeding
- av malformation or aneurysm
- recent surgery/trauma
- hx of CVA; **uncontrolled HTN
precautions: - recent punctures, surgery, trauma, antiplatelet tx
- recent GI/GU bleeding
- Advanced age; high bp
Recteplase considerations
Recombinant deletion mutant of wild type tissue plasminogen activator
- does not have kringle-1, finger, GF domains
- decreased fibrin specificity, higher potency, shorter half life
Tenecteplase MOA
Plasma inactivation via PAI-1
Tenecteplase Indications
Used with UFH, enoxaparin
Tenecteplase Metabolism
Extensive inactivation in the liver
Half life: biphasic—24 minutes then 115 minutes ****
75% achieve patency at 90 minutes
60% TIMI 3 flow
Tenecteplase CI/precautions
CI:
- bleeding
- av malformation or aneurysm
- recent surgery/trauma
- hx of CVA; uncontrolled HTN**
precautions: - recent punctures, surgery, trauma, antiplatelet tx
- recent GI/GU bleeding
- Advanced age; high bp >180/110
Tenecteplase SE
Increased half life
Increased fibrin specificity
Reduced inactivation by plasminogen activation inhibitor 1 (PAI-1)
decrease risk by lowering infusion rate!! **
Tenecteplase considerations
Genetically reengineered alteplase ()
-has 2 AA substitutes and 4 alanine substitutes
produced in Chinese hamster ovary cells
Pathogenesis to MI
Plaque disruption/fissure/erosion
thrombosis formation
Non ST elevation ACS or ST elevation ACS
What % pts with ACS have >= 2 plaques
50%
TIMI Risk Score
more increased needs a more aggressive TX Age >/= 65 >/= 3CAD risk factors Prior Coronary Stenosis >50% ST deviation >/=2 Anginal events in less than 24 hours ASA last 7 days elevated cardiac markers
Class 1 agents for NSTE-ACS
-Aspirin
Clopidogrel if allerigic
Or use with clopidogrel if invasive approach is not planned
Stop clopidogrel 5-7 days before CABG or surgery
-Use GP IIb/IIIa inhibitor if cardiac cath and PCI is planned- max tx 8 days
Class 2a Agents for NSTE-ACS
Use GP IIb/IIIa inhibitor in pts RECEIVING CLOPIDOGREL if cardiac cath and PCI planned
Use GP IIb/IIIa inhibitor in high risk pts if invasive strategy is not planned
Antiplatelet tx functions to
prevent thrombosis from plaque rupture in ACS
Dual or Tripple antiplatelet therapy can reduce odds of vascular caused death, MI or stroke by
22%
What anti platelet combos are there?
ASA + Clopidogrel (one or both)
option to add GP IIb/IIIa inhibitors
caution because increase risk to bleed
