Fibrinolytics.pptx

this ppt about the thrombolytic agents and its mechanism of action, uses, adverse effects and contraindications. this will help to the medical students to understand about the fibrinolytic drugs easily

1. A 58 year old male came to the emergency department with complaints of left sided chest pain radiates to the back and left arm and increased sweating, difficulty in breathing since 4 a.m today. He is a known hypertensive and diabetic for past 10 years under regular treatment, what is your diagnosis ? 1

2. ACUTE MYOCARDIAL INFARCTION 2

3. FIBRINOLYTICS Dr. K. Sathishbabu 2 nd Year Post Graduate Department of Pharmacology 05.02.2020 3

4. Learning Objectives By the end of the session will be able to Understand what is Fibrinolytic system Describe the fibrinolytic drugs & its mechanism Enlist its Uses & Adverse effects 4

5. FIBRINOLYTIC SYSTEM Checks and balances the clotting system Dissolves the clot at the site of damage, once damage is repaired Activators : tPA, Factor XIIa & Kallikrein Inhibitors : α 2 anti plasmin, α 2 macroglobulin 5

6. Plasmin : Enzyme responsible for fibrin degradation Generated from plasminogen by tPA (tissue plasminogen activator) Plasminogen : Inactive form of plasmin Present in circulation as well as bound to fibrin 6

7. tPA (tissue Plasminogen Activator) : Produced by vascular endothelium Selectively activates fibrin bound plasminogen into plasmin Anti plasmin : Present in circulation and inactivates the leaked plasmin & prevents premature lysis of fibrin 7

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9. MECHANISM 9 PLASMINOGEN PLASMIN Fibrin ( S oluble ) Fibrin (Insoluble) Extrinsic activators : Fibrinolytic drugs Eg .: Streptokinase, Alteplase Intrinsic activators: tPA , Factor XIIa , Kallikrein

10. FIBRINOLYTIC DRUGS Streptokinase Urokinase Alteplase Reteplase Tenecteplase Antistreplase 10

11. STREPTOKINASE Obtained from β hemolytic streptococci MOA : Forms 1:1 complex with plasminogen Catalyses 1. Plasminogen (Inactive)  Plasmin (active)  Fibrinolysis 2. Breakdown of fibrinogen 11

12. Non fibrin specific Half life : 60 – 80 mins Use : Myocardial infarction, Deep vein thrombosis & Pulmonary embolism Advantages : Least expensive ; still used in resource poor areas 12

13. Disadvantages : Antigenic ; can cause hypersensitivity Anti streptococcal antibodies – reduce its efficacy Cannot be repeated Fever, Hypotension, arrhythmia 13

14. UROKINASE Cultured from human kidney cells Direct plasminogen activator Can degrade both fibrin & fibrinogen T1/2 : 20 mins Use : Patients whom streptokinase cannot be repeated 14

15. Advantages : Mild f ibrin specific Non antigenic ; Non pyrogenic ; does not produce hypotension Pro urokinase : recombinant form ; more fibrin specific 15

16. ALTEPLASE Recombinant tissue plasminogen activator Produced by recombinant DNA technology from human tissue culture More fibrin specific ; hydrolyze fibrin only (not fibrinogen) Rapidly activates plasminogen ; t1/2 is 5–10 mins 16

17. Advantages : Non antigenic Superior in dissolving old clots Disadvantages : Higher incidence of reocclusion ; needs I.V heparin co administration Fever, Nausea, mild hypotension Quite expensive 17

18. RETEPLASE Modified recombinant tissue plasminogen activator Less specific for fibrin bound plasminogen Long acting ; t1/2 is 15 – 20 mins Dose : 10 mg over 10 min repeated after 30 min A/E : fever, hypotension 18

19. TENECTEPLASE Genetically engineered mutant form of native rt -PA IV single bolus dose 50mg over 10 seconds Advantages : High fibrin selectivity Long acting ; t1/2 is 2hours Resistance to PAI – 1 ( plasminogen activator inhibitor 1) 19

20. Disadvantages : Very expensive Risk of cranial bleeding 20

21. ANTISTREPLASE Anisolyated plasminogen streptokinase activator complex Consists of purified human plasminogen with bacterial streptokinase in which the active site of plasminogen has been protected by anisoylation (a process of acetylation) 21

22. Mechanism : Administration Acyl group hydrolyses spontaneously Release the streptokinase – proactivator complex fibrinolysis 22

23. Advantages : Synthesized to improve the pharmacokinetics of streptokinase-proactivator complex More fibrin specificity Long acting (t1/2 > 90mins) A/E : Hypersensitivity, Hypotension, Bleeding etc. 23

24. USES OF FIBRINOLYTICS Acute Myocardial Infarction Deep Vein Thrombosis Pulmonary embolism Peripheral arterial occlusion Stroke 24

25. CONTRAINDICATIONS Intracranial haemorrhage / Intracranial tumour Ischemic stroke / Head injury in past 3 months Vascular abnormalities Bleeding disorders Peptic ulcer Esophageal varices Any wound or recent fracture Tooth extraction Major surgery within 3 weeks Uncontrolled hypertension Pregnancy 25

26. SUMMARY tPA – main activator of fibrinolytic system Streptokinase – antigenic ; non specific Urokinase – fibrin specific ; less side effects Alteplase – very short acting ; risk of reocclusion Reteplase – less fibrin specific ; long acting 26

27. Tenecteplase : High fibrin selectivity ; long acting ; resistance to PAI 1 Antistreplase : modified anisolyated streptokinase to improve pharmacokinetics 27