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

1. Active internal bleeding 2. Bleeding diatheses 3. Pregnancy4. Uncontrolled hypertension 5. CPR (Cardio-plumonary resuscitation)6. Recent major surgery or Eye surgery 7. Recent hemorrhagic stroke

8- dissecting aorta aneurysm9- 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

Good luck