Thrombolytics and Fibrinolytics Mechanism

Thrombolytics and Fibrinolytics

• Agents used for lysis of recently formed clots (less than 12 hours)

Fibrinolytic System

• Liver secrets plasminogen, which binds to fibrin threads of the clot
• Plasminogen is activated by tissue plasminogen activator into plasmin
• Plasmin causes lysis of the clot

Thrombolytics and Fibrinolytics Mechanism

• Act by activating plasminogen into plasmin

Classification

• Non-fibrin selective: activate circulating plasminogen all over the body, systemic effect (e.g., Streptokinase and Urokinase)
• Fibrin selective: selectively activate plasminogen at the site of thrombus only, local effect (e.g., Recombinant tissue plasminogen activator)

Administration

• Both non-fibrin selective and fibrin selective must be administered by I.V. route

Non-Fibrin Selective Thrombolytic Drugs

• Streptokinase: protein isolated from beta hemolytic streptococci, may cause allergy and fever in some people
• Urokinase: enzyme isolated from human urine

Fibrin Selective Thrombolytic Drugs

• Recombinant tissue plasminogen activator: human proteins produced by genetic engineering (e.g., Alteplase and Reteplase)

Pharmacological Uses of Thrombolytic Drugs

• Life-saving in emergency thrombo-embolic disorders
• Deep venous thrombosis
• Severe pulmonary embolism
• Acute myocardial infarction
• Peripheral arterial thrombosis
• In cases of acute myocardial infarction, thrombolytic drugs should be given within 6 hours from thrombus formation

Side Effects of Thrombolytic Drugs

• Bleeding is the major side effect
• Risk of bleeding is high with Streptokinase and Urokinase, and low with recent recombinant tissue plasminogen activators
• Streptokinase can cause allergy, fever, and hypotension during I.V.