ROZAIMAH ZAIN-HAMID. Department of Pharmacology and Therapeutics Faculty of Medicine, Universitas Sumatera Utara
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1 ROZAIMAH ZAIN-HAMID Department of Pharmacology and Therapeutics Faculty of Medicine, Universitas Sumatera Utara
2 Drugs Used in Disorders of Coagulation Fibrinolytic drugs Anti-thrombotic thrombotic drugs Anticoagulant drugs Drugs used in bleeding disorders d
3 Fibrinolytic drugs Lyse thrombi (i.v administration: generalized lytic state) Catalyzing the formation of the serine protease plasmin from its precursor zymogen, plasminogen
4 Fibrinolytic drugs Streptokinase Anistreplase Urokinase Tissue Plasminogen Activator (t-pa)
5 Approaches to reduce non-selective effects of fibrinolytic drugs A new generation of prothrombolytic drugs, tissue plasminogen activator, may induce thrombolysis with <<< systemic fibrinolysis or fibrinogen breakdown Intra-arterial arterial use (intracoronary inject.), may systemic bleeding by localizing the drug
6 Streptokinaset
7 Streptokinase A A protein synthesizes by streptococcus combines with the proactivator plasminogen The enzymatic complex catalyze conversion plasminogen active plasmin
8 Streptokinase Absence of inhibitors for streptokinase proactivator complex, permit their use clinically Administered by i.v infusion of a loading dose : 250,000units, 000 followed by 100,000 units/h for hours
9 Urokinase
10 Urokinase A human enzyme synthesized by the kidney Directly converts plasminogen active plasmin
11 Urokinase Absence of inhibitors for urokinase, permit their use clinically Plasmin formed inside a thrombus by activators, is protected from plasma antiplasmin allows it to lyse the thrombus from within
12 Urokinase Requires a loading dose : 300,000units, given over 10 minutes & maintenance dose of 300,000units/h 000units/h for 12 hours
13 Anistreplase
14 Anistreplase (Anisolated Plasminogen Streptokinase Activator Complex /APSAC) Consist a complex of purified human plasminogen & bacterial streptokinase Acylated to protect the enzyme s active site
15 Administered anistreplase The acyl group spontaneously hydrolizes Freeing the activated streptokinase-proactivator proactivator complex
16 Anistreplase Allow for rapid i.v injection Greater clot selectivity (more activity on plasminogen associated with clot than on free plasminogen in the blood) More thrombolytic activity
17 Anistreplase Is given as a single i.v injection: 30 units over 3-5 minutes
18 Tissue Plasminogen Activator (t-pa)
19 Tissue Plasminogen Activators (t-pa) To activate plasminogen that t bound to fibrin i Human t-pa is manufactured Recombinant DNA technology
20 Tissue Plasminogen Activators (t-pa) Is given by i.v injection: 60 mg over the 1 st hour & 40 mg at a rate of 20 mg/h
21 Clinical application of fibrinolytic therapy Early treatment for pulmonary embolus may improve survival & may preserve long-term pulmonary function Should be followed by administration of heparin & then warfarin
22 Warning: fibrinolytic therapy Concomitant invasive prosedure must be avoided Bleeding
23 Contraindication: fibrinolytic therapy After recent surgery Metastatic cancer, stroke Underlying hemorrhagic disorders Universitas Sumatera Utara
24 Syafiuddin San & Rozaimah San, Kyoto, Nov. 06 Japan. Arigato Gozaimasu
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