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Fibrinolytics & antifibrinolytics
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- 3. Drugs used tolyse thrombi to recanalize occluded blood vessels
- 4. Works by activating thenatural fibrinolytic system
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- 6. PLASMINOGEN FIBRIN FRAGMENTS FIBRIN PLASMIN ACTIVATORS t-PA, Kallikrein,Factor Xa INHIBITORS α2Antiplasmin α2 Macroglobulin
- 7. • Venous thrombilysed more easily • Recent thrombi respond better • Little effect on thrombi >3 days old
- 8. Clinically important fibrinolyticsare, • Streptokinase • Urokinase • Alteplase (rt PA) • Reteplase • Tenecteplase
- 9. Streptokinase • Source:β haemolyticstreptococci group C • Inactive as such • Combines with circulating plasminogen forms activator complex proteolysis of plasminogen Active plasmin • Cheap,widely used in India
- 10. Disadvantages 1.Activates both circulating& fibrin bound plasminogen Depletion of circulating plasminogen → bleeding 2. Antistreptococcal Abs from past infections inactivate considerable fraction of initial dose , loading dose needed 3.AntigenicHSR & anaphylaxis when used for 2nd time 4.Repeat doses less effective due to neutralisation by Abs
- 11. Urokinase • Isolated fromhuman urine ,now from cultured human kidney cells • Activates plasminogen directly • Moderately specific to fibrin bound plasminogen • Nonantigenic • Indicated in whom streptokinase has been used for an earlier episode
- 12. Alteplase Produced by recombinant DNA technology •Nonantigenic •Shortt1/2 so given as slow IV infusion •Expensive Reteplase Produced by recombinant DNA technology •Modified form of rt-PA •Long acting •So given as bolus dose repeated in 30 min
- 13. Tenect eplase Produced by r DNA technology •Mutantvariant of rt-PA •Long duration of action •Single IV bolus
- 14. USES 1.Acute MI – –chief indication,alternate to emergency percutaneous coronary intervention with stent placement – Golden period-1hr,Better results- within 3hrs – Timelag in starting infusion is critical in • Reducing area of necrosis • Preserving ventricular function • Reducing mortality
- 15. 2.Deep vein thrombosis 3.Pulmonaryembolism 4.Peripheral arterial occlusion 5.Stroke- – rt-PA –approved for treatment of ischaemic stroke – treated within 3 hours of onset – intracranial hemorrhage has to be ruled out
- 16. CONTRAINDICATIONS • All situationswhere the risk of bleeding is increased – Recent trauma – Surgery – Biopsy – Hemorrhagic stroke – Peptic ulcer – Severe hypertension – Aneurysms – Bleeding disorders – Diabetes – Acute pancreatitis – pregnancy
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- 18. Drugs which inhibit plasminogenactivation & dissolution of clot
- 19. EPSILON AMINO-CAPROIC ACID(EACA) • Analogueof lysine • Binds to lysine binding sites of plasminogen & plasmin so that it cannot bind to fibrin & lyse the clot
- 20. USES • Overdose offibrinolytics • To prevent recurrence of G.I & subarachnoid hemorrhage • Certain traumatic & surgical bleedings like prostatectomy,tooth extraction in haemophiliacs • Abruptio placentae,PPH & menorrhagia
- 21. Adverse Effects • Inhematuria –ureteric obstruction by the unlysed clots • Intravascular thrombosis • Hypotension,bradycardia,arrhythmias • Caution in impaired renal function • Myopathy
- 22. TRANEXAMIC ACID • MOA-similarto EACA • 7 times potent than EACA • Preferred drug for bleeding due to – Fibrinolytic drugs – Cardiopulmonary bypass surgery – Tonsillectomy,prostatic surgery,tooth extraction in haemophiliacs – Menorrhagia – Recurrent epistaxis,hyphema due to ocular trauma,peptic ulcer
- 23. Adverse Effects • Nausea •Diarrhoea • Thromboembolic events • Disturbed colour vision • Allergic reactions • Thrombophlebitis
- 24. PLASMINOGEN FIBRIN FRAGMENTS FIBRIN PLASMIN ACTIVATORS INHIBITOR • Streptokinase • Urokinase •Alteplase • Reteplase • Tenecteplase • EACA • Tranexaemic acid
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