MT2_7_Thrombolytics Pharma

Question 1

Describe the MOA of fibrinolysis

Answer 1

• dissolves fibrin by activating plasmin by turning plasminogen to plasmin (tpa and urokinase)

Question 2

Describe the MOA of thrombolytics

Answer 2

• they facilitate the breakdown of fibrin strands by converting plasminogen to plasmin

Question 3

What are the main indications for thrombolytics?

Answer 3

• ST elevation
• pulmonary embolism
• peripheral arterial and venous thromboembolism
• ischemic stroke
• catheter occlusions

Question 4

Name the thrombolytics

Answer 4

1: streptokinase, urokinase (not fibrin specific, so targets all plasminogen)
2: alteplace (fibrin specific)
3: reteplase, tenecteplase (fibrin specific)

Question 5

When is streptokinase CI?

Answer 5

• within 6 months of previous exposure

Question 6

TPA does not activate plasminogen unless___

TPA+plasminogen = conformational change of clot increasing..

Answer 6

• fibrin is around

- catalytic efficiency

Question 7

Indications for TPA?

Answer 7

• STEMI
• Ischemic Stroke
• PE
• Catheter clearance

Question 8

TPA clearance? Excretion?

Answer 8

• rapidly cleared, fibrinolytic activity persists for up to 1 hour
• hepatic excretion

Question 9

What is the dose for TPA for ischemic stroke?

Answer 9

• 0.9 mg/kg max 90mg

- not recommended in initiation within 24 hours of starting heparin

Question 10

Exclusions for TPA use in stroke?

Answer 10

• stroke resolved
• serious brain trauma in the past 3 months
• bleeding
• BP greater than 185
• hyper/hypoglycemia that explains neurological defects

Question 11

Differentiate between massive PE and submissive PE

Answer 11

• Massive: hemodynamically unstable (hypotension, SBP is less than 90)
• submassive : stable but with RV dysfunction

Question 12

For a massive PE, what is the dose?

Answer 12

UNSTABLE

• 100mg IV over 2 hours
• initiate IV hep after alteplace infusion when aPTT is less than 2x normal or less

Question 13

When to administer TPA in a STEMI? Administer concurrent____

Answer 13

within 30 minutes

- anticoagulation, aspirin, P2y12 inhibitor

Question 14

Difference between reteplase and alteplace?

Answer 14

• lack of fibrin binding domain and fibrin specificity than TPA
• has a longer half life and dual bolus dosing

Question 15

Dosing of reteplase for a STEMI?

Answer 15

• 10 units IV over 2 minutes , then a second dose 30 min later

Question 16

SE of reteplase?

Answer 16

• bleeding and anaphylaxis

Question 17

Compared to TPA, how is tenecteplase better?

Answer 17

• longer half life and more fibrin specific , allowing for single bolus dosing
• (it decreases plasma clearance, increases fibrin specificity, and decreases sensitivity to plasminogen inhibitor)

Question 18

When should tenecteplace be administered?

Answer 18

within 30 min arrival to hospital

give with anticoag, aspirin, and P2Y 12 inhibitor

Question 19

When using a thrombolytic in a STEMI, how long do we give an anticoagulant, and why is it important to do so?

Answer 19

• 48 hrs, up to 8 days
• to improve vessel potency and prevent reocclusion due to the possibility of a refund effect , activating thrombin = clotting

Question 20

Absolute STEMI CI for thrombolytics ?

Answer 20

• prior intercerebral hemmorage
• cerebral vascular lesion
• malignancy intracranial neoplasm
• ischemic stroke within 3 months
• aortic dissection
• active bleeding
• closed head or facial trauma within 3 months
• intracranial/intraspinal surgery within 2 months
• severe uncontrolled HTN

Question 21

How do you measure response?

Answer 21

• TIMI flow , where 3 is normal flow, and 2 is partial flow

Question 22

What do we want to see in a thrombolytic improvement?

Answer 22

• resolution of more than 70% ST elevation within 1.5 hours
• chest pain improvement
• repercussion arrhythmias

(partial response is less than 50% ST resolution, no reprofusion)

Question 23

When monitoring, what can be affected?

Answer 23

• decrease in fibrinogen

- PT, aPTT, and bleeding time can increase

Question 24

Which agent has more fibrin specificity?

Answer 24

• tenecteplase, single IV bolus, compared to TPA