Thrombolytics + extra (STEMI/NSTEMI/UA)

Question 1

Thrombolytics

Answer 1

Alteplase
Reteplase
Tenecteplase

Question 2

Thrombolytics Indications

Answer 2

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

Question 3

Thrombolytics MOA

Answer 3

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

Question 4

Lytics can be used in ____ but not ___ or __

Answer 4

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 ☹

Question 5

Lytics Considerations

Answer 5

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!

Question 6

Lytics reversal?

Answer 6

Lytics CAN be reversed with AMINOCAPROIC ACID ☺

• binds to lysine on plasminogen and plasmin
• prevents interaction with fibrin

Question 7

Alteplase MOA

Answer 7

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

Question 8

Alteplase indication

Answer 8

Given with UFH or enoxaparin

LESS active on systemically circulating plasminogen

Question 9

Alteplase Metabolism

Answer 9

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

Question 10

Alteplase clearance

Answer 10

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

Question 11

Alteplase CI/ Precautions

Answer 11

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

Question 12

Alteplase considerations

Answer 12

Replaced streptokinase bc of fibrin secificty

Question 13

Recteplase MOA

Answer 13

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

Question 14

Recteplase indications

Answer 14

Given with UFG, enoxaparin

Question 15

Recteplase Metabolism

Answer 15

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

Question 16

Recteplase CI/precautions

Answer 16

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

Question 17

Recteplase considerations

Answer 17

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

Question 18

Tenecteplase MOA

Answer 18

Plasma inactivation via PAI-1

Question 19

Tenecteplase Indications

Answer 19

Used with UFH, enoxaparin

Question 20

Tenecteplase Metabolism

Answer 20

Extensive inactivation in the liver

Half life: biphasic—24 minutes then 115 minutes ****
75% achieve patency at 90 minutes
60% TIMI 3 flow

Question 21

Tenecteplase CI/precautions

Answer 21

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

Question 22

Tenecteplase SE

Answer 22

Increased half life
Increased fibrin specificity
Reduced inactivation by plasminogen activation inhibitor 1 (PAI-1)

 decrease risk by lowering infusion rate!! **

Question 23

Tenecteplase considerations

Answer 23

Genetically reengineered alteplase ()
-has 2 AA substitutes and 4 alanine substitutes

produced in Chinese hamster ovary cells

Question 24

Pathogenesis to MI

Answer 24

Plaque disruption/fissure/erosion
thrombosis formation
Non ST elevation ACS or ST elevation ACS

Question 25

What % pts with ACS have >= 2 plaques

Answer 25

50%

Question 26

TIMI Risk Score

Answer 26

``` 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 ```

Question 27

Class 1 agents for NSTE-ACS

Answer 27

-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

Question 28

Class 2a Agents for NSTE-ACS

Answer 28

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

Question 29

Antiplatelet tx functions to

Answer 29

prevent thrombosis from plaque rupture in ACS

Question 30

Dual or Tripple antiplatelet therapy can reduce odds of vascular caused death, MI or stroke by

Answer 30

22%

Question 31

What anti platelet combos are there?

Answer 31

ASA + Clopidogrel (one or both) option to add GP IIb/IIIa inhibitors caution because increase risk to bleed