MT2_7_Thrombolytics Pharma Flashcards
Describe the MOA of fibrinolysis
- dissolves fibrin by activating plasmin by turning plasminogen to plasmin (tpa and urokinase)
Describe the MOA of thrombolytics
- they facilitate the breakdown of fibrin strands by converting plasminogen to plasmin
What are the main indications for thrombolytics?
- ST elevation
- pulmonary embolism
- peripheral arterial and venous thromboembolism
- ischemic stroke
- catheter occlusions
Name the thrombolytics
1: streptokinase, urokinase (not fibrin specific, so targets all plasminogen)
2: alteplace (fibrin specific)
3: reteplase, tenecteplase (fibrin specific)
When is streptokinase CI?
- within 6 months of previous exposure
TPA does not activate plasminogen unless___
TPA+plasminogen = conformational change of clot increasing..
- fibrin is around
- catalytic efficiency
Indications for TPA?
- STEMI
- Ischemic Stroke
- PE
- Catheter clearance
TPA clearance? Excretion?
- rapidly cleared, fibrinolytic activity persists for up to 1 hour
- hepatic excretion
What is the dose for TPA for ischemic stroke?
- 0.9 mg/kg max 90mg
- not recommended in initiation within 24 hours of starting heparin
Exclusions for TPA use in stroke?
- stroke resolved
- serious brain trauma in the past 3 months
- bleeding
- BP greater than 185
- hyper/hypoglycemia that explains neurological defects
Differentiate between massive PE and submissive PE
- Massive: hemodynamically unstable (hypotension, SBP is less than 90)
- submassive : stable but with RV dysfunction
For a massive PE, what is the dose?
UNSTABLE
- 100mg IV over 2 hours
- initiate IV hep after alteplace infusion when aPTT is less than 2x normal or less
When to administer TPA in a STEMI? Administer concurrent____
within 30 minutes
- anticoagulation, aspirin, P2y12 inhibitor
Difference between reteplase and alteplace?
- lack of fibrin binding domain and fibrin specificity than TPA
- has a longer half life and dual bolus dosing
Dosing of reteplase for a STEMI?
- 10 units IV over 2 minutes , then a second dose 30 min later
SE of reteplase?
- bleeding and anaphylaxis
Compared to TPA, how is tenecteplase better?
- 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)
When should tenecteplace be administered?
within 30 min arrival to hospital
give with anticoag, aspirin, and P2Y 12 inhibitor
When using a thrombolytic in a STEMI, how long do we give an anticoagulant, and why is it important to do so?
- 48 hrs, up to 8 days
- to improve vessel potency and prevent reocclusion due to the possibility of a refund effect , activating thrombin = clotting
Absolute STEMI CI for thrombolytics ?
- 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
How do you measure response?
- TIMI flow , where 3 is normal flow, and 2 is partial flow
What do we want to see in a thrombolytic improvement?
- 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)
When monitoring, what can be affected?
- decrease in fibrinogen
- PT, aPTT, and bleeding time can increase
Which agent has more fibrin specificity?
- tenecteplase, single IV bolus, compared to TPA
