Fibrinolytics Overview

Study Notes

Used to dissolve thrombi and recanalize occluded blood vessels, primarily in coronary arteries.
Therapeutic in nature, activating the body's natural fibrinolytic system.
More effective for venous thrombi than arterial; recent thrombi respond best.
Ineffective on thrombi older than 3 days.

Alteplase (rt-PA): Recombinant drug, fibrin-specific, plasma half-life of 4-8 min, needs slow IV infusion.
Streptokinase: Derived from group C β-hemolytic Streptococci, combines with plasminogen, non-fibrin specific leading to bleeding risk.
Reteplase: Modified rt-PA, longer acting, allows for bolus administration.
Urokinase: Isolated from human urine, activates plasminogen directly, has a short plasma half-life (10-15 min).
Tenecteplase: Genetically engineered, higher fibrin selectivity, given as a single IV bolus.

Acute Myocardial Infarction (MI): Primary indication with 50-90% recanalization success. Contraindications include increased risk of hemorrhage.
Deep Vein Thrombosis: Successful treatment in 60% of cases, aids in preserving venous valves, reduces pulmonary embolism risk.
Pulmonary Embolism: Indicated for large, life-threatening cases.
Ischaemic Stroke: Use remains controversial due to risks of intracranial hemorrhage.
Peripheral Arterial Occlusion: Effective in 40% of acute limb occlusions treated within 72 hours.

Ideal for STEMI cases; limited benefit in non-STEMI with increased hemorrhage risk.
Restoration of flow within the first hour yields best outcomes.
Thrombolysis may be favored within 1-2 hours of onset.
After 3 hours, percutaneous coronary intervention (PCI) is preferred.
PCI has lower bleeding risk and better long-term outcomes compared to thrombolytics.

Epsilon Amino-Caproic Acid (EACA): Lysine analogue, inhibits plasminogen activation, used to counteract fibrinolysis-related bleeding.

Interfere with platelet function to prevent thromboembolic disorders.
Aspirin: Irreversibly inhibits COX-1, reducing thromboxane A2 (TXA2) synthesis, prolonging bleeding time up to 5-7 days.
Dipyridamole: Increases cAMP in platelets, used alongside warfarin to lower thromboembolism risk.
Ticlopidine: Blocks ADP binding to platelets, enhances effects of aspirin, used for stroke prevention and unstable angina.
Platelet aggregation involves complex interactions with various receptors, particularly in the presence of vascular injury.

Aspirin: Effective at doses as low as 40 mg, with maximal effect at 75-150 mg.
Dipyridamole: Enhances the effects of other antiplatelet drugs, generally used in conjunction with aspirin.
Ticlopidine: Targets P2Y12 receptors, causing prolonged platelet inhibition and cumulating effects over time.