Chap 34: Fibrinolytic drugs

Introduction
- rapidly lyse thrombin by catalysing plasminogen --> plasmin
- plasmin itself cannot be used due to inhibiting enzymes

Pharmacology
- streptokinase

• made by streotpcocci - converts inactive plasminogen to plasmin

- urokinase

• human enzyme synthesized by kidney

- anistreplase

• anisoylated plasminogen streptokinase activator complex
• complex of purified human plaminogen + bacterial streptokinase
• allows rapid IV injection, allows greater clot selectivity

- tissue plasminogen activators

• preferentially activates plasminogen THAT IS BOUND TO FIBRIN
• in theory - only lyses formed thrombus - avoids systemic activation
• alteplase - recombinant DNA technology --> human tPA
• reteplase - same as alteplase with several amino acids deleted - less expensive to produce but less fibrin-specific than t-PA
• tenecteplase - mutant form of t-PA with longer T1/2

Thrombolytic drugs for AMI
- 20% reduction in mortality for pt with AMI
- PCI (intervention) = PTCA +- stent - better but if not available = thrombolysis
- pt selection is critical

• dx of AMI - clinical + ECG
• pt with STEMI and new onset BBB has best outcomes
• earlier the better, within 6 hrs onset of AMI

Other indication and dosage
- PE with hemodynamic instability
- severe DVT - SVC syndrome, ascending thrombophlebitis of iliofemoral vein - severe edema
- intraarterial PVD
- AMI:

• streptokinase: loading dose 250K units, then 100K U/hr for 24-72 hrs; beware antistreptococcal antibodies - fever, allergic reaction

- acute ischaemic stroke

• <3hrs>
• ensure not hemorrhagic infarct - better outcome
• check dosage as higher dosage 1.5million units --> increased bleeding risk

- d