Thrombolytic drugs BY :DR. ISRAA OMAR

Fibrinolysis and thrombolysis It is initiated concomitantly with coagulation cascade, resulting in the formation of active plasmin ,which digest fibrin . The main drug of this group are streptokinase and tissue plasminogen activator (tPA),for example alteplase The main use is in acute STMI ,acute stroke ,clearing cannula ,arterial thromboembolism and life threatening DVT and pulmonary embolism

Thrombolytic drugs – mechanism of action

Thrombolytic drugs – mechanism of action

Thrombolytic drugs – mechanism of action

1. Streptokinase Is a non –enzyme protein extracted from culture of streptococci It form stable complex with plasminogen and gains enzymic activity ;then causes fibrinolysis The major adverse effect is bleeding include GI Hemorrhage and stroke Hemorrhage can be treated with traneximic acid Hypotension and hypersensitivity may also recorded

2. Alteplase and duteplase Both are recombinant tissue plasminogen activators. Alteplase is a single chain where as duteplase is a double chain They preferentially plasminogen that is bound to fibrin ,they are said to be clot selective . They dissolve formed thrombus and avoid systemic activation of plasminogen They can cause hemorrhage but less than streptokinase No hyper sensitivity reaction occur with them

Contraindications to thrombolytic therapy Active internal bleeding Bleeding diatheses Pregnancy Uncontrolled hypertension CPR (Cardio-plumonary resuscitation) Recent major surgery or Eye surgery Recent hemorrhagic stroke 8- dissecting aorta aneurysm 9- Brain tumors

Treatment of bleeding BY:DR ISRAA OMAR

Drugs for Bleeding Disorders Coagulation Factors Inhibitors of fibrinolysis Vitamin K Factor VIII Factor IX Desmopressin Aminocaproic Acid Tranexamic Acid Aprotinin

1. Antiplasmin drugs Aminocaproic acid and tranexamic acid both are synthetic agents. They are orally active Mechanism of action They are lysine analogs that bind to plasminogen and plasmin, thus blocking both the conversion of plasminogen to plasmin and the binding of plasmin to target fibrin. The drugs are potent inhibitors of fibrinolysis and can reverse states associated with excessive fibrinolysis.

Adverse effects Intravascular thrombosis, a major adverse effect due to inhibition of plasminogen activator. Myopathy with rhabdomyolysis (rare) Rhabdomyolysis is the breakdown of muscle tissue that leads to the release of muscle fiber contents into the blood.

Therapeutic uses Bleeding due to fibrinolytic therapy or surgery in hemophiliacs. Bleeding due to other causes (surgery, radiation, intracranial aneurism, cancer chemotherapy, etc.) (benefits in these settings are limited)

2. Aprotinin It stops bleeding by blocking plasmin It can inhibit streptokinase It is used to reduce blood loss in patients undergoing cardiopulmonary bypass surgery Side effect include anaphylactic reaction if there is previous exposure within 12 month , renal dysfunction is also reported with the use of this drug

3. Protamine sulfate Antagonizes the anticoagulant effect of heparin It is derived from fish sperm and testes and has a high content of arginine which make it basic drug It is positive charge neutralize the negative charge of heparin thus making a stable complex and prevent the action of heparin Side effect include dyspnea, flushing, hypotension and bradycardia especially when injected rapidly

4. Vitamin k (phytonadione) It antagonize the action of oral anticoagulant The action of vitamin k start after 24 hours; thus, if immediate action is required, fresh frozen plasma should be infused

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