Fibrinolytic drugs

Question 1

What are the two major classes of fibrinolytics?

Answer 1

• kinases

* Tissue plasminogen activators (tPA)

Question 2

Name two kinases

Answer 2

• Streptokinase

* Urokinase

Question 3

Name two tPAs

Answer 3

• Alteplase

* Reteplase

Question 4

What are the uses of the fibrinolytic drugs?

Answer 4

•Breakdown of a pathogenical thrombus:

• systemically
• locally - Catheter directed

Question 5

What is the mechanism of action of the tPA derivatives?

Answer 5

• activate plasminogen so plasmin is cleaved from plasminogen
• Plasmin breaks down fibrin
• Relatively selective for clot bound plasminogen so there is minimal unwanted fibrogenolysis

Question 6

When can streptokinase be rendered ineffective?

Answer 6

After a strep infection or with previous use of streptokinase as it is antigenic (urokinase however is not antigenic)

Question 7

What is the half life of the kinases?

Answer 7

15-20 minutes

Question 8

How do you give kinases?

Answer 8

As a bolus dose then infusion

Question 9

What are the problems with the kinases?

Answer 9

• Streptokinase is antigenic
• Significant bleeding risk
• Cell derivatives

Question 10

What are the differences between alteplase and reteplase?

Answer 10

• Reteplase has a longer half life (alteplase only 4-5 minutes)
• Reteplase is bolus only whereas alteplase is given as a bolus then infusion

Question 11

What are the indications for tPA derivatives?

Answer 11

• Acute myocardial infarction in patients not suitable for PCI within 12 hours of onset
• Ischaemic stroke within 4.5 hours of onset of symptoms
• Massive pulmonary embolism with haemodynamic instability

Question 12

What are the side effects of the tPA derivatives?

Answer 12

•Stroke 
•Increased bleeding risk (any organ, particularly intracerebral) 
 - large ischaemic stroke
 - elderly 
 - later administration 
 - uncontrolled diabetes

Question 13

What are the absolute contraindications to tPA derivatives?

Answer 13

• Haemorrhagic stroke or stroke of unknown origin
• Ischaemic stroke in preceding 6 months
• CNS damage or neoplasms
• Major traumatised or surgery or head injury within preceding 3 weeks
• GI bleed in the last month
• Known bleeding disorder
• Aortic dissection

Question 14

What are the pros of catheter directed thrombolysis?

Answer 14

• Smaller doses required
• Administered directly into vessel containing thrombosis
• Less systemic effect
• Paradoxically not necessarily less bleeding

Question 15

What are the uses of catheter directed thrombolysis?

Answer 15

• Acute limb ischaemia
• Massive DVT
• Blocked CVC (central venous catheter)