Thrombolytic drugsBY :DR. ISRAA OMAR

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

FIBRINOLYSIS AND THROMBOLYSIS

Thrombolytic drugs – mechanism of action

Thrombolytic drugs – mechanism of action

Thrombolytic drugs – mechanism of action

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

Streptokinase

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

Alteplase and duteplase

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

Contraindications to thrombolytic therapy

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

Aminocaproic acid and tranexamic acid 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)

Antiplasmin drugs

Both are synthetic agents Work by inhibition of plasminogen activation They are orally active A potential side effect of treatment is

intravascular thrombosis

Aminocaproic acid and traneximic acid

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

Aprotinin

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

Protamine sulfate

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

Vitamin k (phytonadione)

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