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anti platelet drugs

1. Antiplatelet drugs Dr.VANITHA . MD

2. Introduction Initial hemostatic plug at vascular injury site In pathological thrombosis – MI, stroke, peripheral vascular thrombosis Platelet mass – main part of arterial thrombus – antiplatelet drugs effective

3. Mechanism of action

4. Classification

5. Aspirin Inhibits COX1 & TXA2 irreversibly Other NSAIDs - reversible inhibition of COX Platelet cannot synthesis fresh enzyme Prolong effect for 5-7 days (life span of platelets) Inhibits TXA2 in platelets at low dose 75-150 mg /day selective action on platelet Higher dose - decrease TXA2, PGI2

6. MOA of aspirin

7. Side effects of aspirin Bleeding

8. Dipyridamole Inhibits PDE, increase cAMP , potentiates PGI2, prevent platelet aggregation Coronary vasodilator Used with warfarin , in prosthetic heart valves. 150-300mg/day Coronary steal phenomenon, precipitates angina, headache, tachycardia

9. Ticlopidine Prodrug , Irreversible blockade of P2Y12 receptor Inhibits ADP induced platelet aggregation Synergistic action with aspirin dose 250 mg BD Effect persists several days after discontinuation

10. Ticlopidine side effects Neutropenia Thrombocytopenia Haematological monitoring every 2 wks Diarrhoea, vomiting, abdominal pain Headache, tinnitus, rash Bleeding, jaundice

11. Clopidogrel Congener of ticlopidine, prodrug Safe, better tolerated Aspirin + clopidogrel Less BM toxicity- neutropenia, thrombocytopenia dose 75 mg od

12. Prasugrel Prodrug Potent, rapid action than clopidogrel Ticagrelor very rapid onset, potent

13. GP IIb/IIIa receptor antagonist Receptor for fibrinogen Key receptor for platelet aggregation Block aggregation induced by all agonists ( ADP, 5HT, TXA2 , Thrombin, collagen)

14. Abciximab Chimeric monoclonal antibody against GP receptor Blocks both fibrinogen & VWF Non antigenic As infusion. Cause thrombocytopenia, bleeding, constipation, ileus, arrhythmias Expensive, used in PCI with stent placement

15. GP receptor antagonist Eptifibatide – synthetic peptide Tirofiban - nonpeptide Inhibits fibrinogen only infusion

16. Uses of antiplatelet drugs Coronary artery disease- MI, unstable angina Primary and secondary prevention of MI Low dose aspirin immediately after MI reduce mortality, prevent re infarction Continued indefinitely

17. Coronary artery disease

18. Coronary angioplasty, stents abciximab + aspirin Lowers restenosis, stent thrombosis

19. stents

20. Coronary artery bypass To maintain patency of recanalised coronary artery Implanted bypass vessel Aspirin + ticlopidine / clopidogrel Abciximab + aspirin + heparin reduce restenosis Reduce MI

21. Coronary bypass implants

22. Prosthetic heart valves aspirin + warfarin – reduce microthrombi, embolism

23. Prosthetic heart valves

24. Arteriovenous shunts To maintain the patency of chronic arteriovenous shunts For haemodialysis, vascular graft

25. Cerebrovascular disease Reduce the incidence of TIA Stroke due to thrombosis

26. Deep vein thombosis

27. Venous thromboembolism Used prophylactically

28. Side effects Bleeding Skin rash Diarrhoea , vomiting, abdominal pain Headache, tinnitus Neutropenia , thrombocytopenia, jaundice

29. Antiplatelet drugs & surgery Stop treatment 7 days before surgery Monitor bleeding time

30. FIBRINOLYTICS Used to lyse the thrombi/clot to re canalize the occluded blood vessel (mainly coronary artery) Work by activating the Fibrinolytic system More therputic than prophylactic • S TREPTOKINASE • U ROKINASE • R ETEPLASE (analogue of alteplase ) • A LTEPLASE (t- PA ) • T ENECTEPLASE

31. Streptokinase Obtained from β - hemolytic streptococci Binds with circulating plasminogen to form complex that activates plasminogen to plasmin t ½ = 30 -80 min Antigenic , Pyrogenic Destroyed by circulating anti streptococcal Antibodies(Past infection) Hypotension & arrhythmia can occur

32. Streptokinase Uses Acute myocardial infarction 7.5 to 15 lac IU; I.V over 1 hr period Deep vein thrombosis , Pulmonary embolism Adverse effects Bleeding, hypotension, allergic reactions, fever, arrhythmias Contraindications Recent trauma, surgery, abortion, stroke, severe hypertension, peptic ulcer, bleeding disorders Can not used for second time

33. . Urokinase Enzyme isolated from human urine, now prepared from cultured human kidney cells Direct plasminogen activator t ½ of 10 to 15 min Non antigenic, Non allergenic Fever can occur, but hypotension rare Indicated in patients in whom streptokinase has been given for an earlier episode

34. Alteplase r ecombinant t issue P lasminogen A ctivator( rt -PA ) Selectively activates plasminogen bound to fibrin Non antigenic ,not destroyed by antibodies Rapid acting, more potent Superior in dissolving old clots Short half life 4-8 min Nausea, mild hypotension, fever may occur Expensive

35. Newer recombinant tissue plasminogen activators Reteplase : – Modified rt -PA – Longer half life 15 -20 min, but less specific for fibrin bound plasminogen Tenecteplase : – Genetically engineered mutant form of alteplase – Higher fibrin selectivity and longer half life – 2 hrs – only fibrinolytic injected iv single bolus dose 0.5 mg/kg sufficient – Very expensive

36. Uses of fibrinolytics Acute myocardial infarction Deep vein thrombosis Pulmonary embolism Peripheral arterial occlusion Ischemic Stroke

37. contraindications to thrombolytic therapy H/o intracranial haemorrage H/o ischemic stroke in past 3 months H/o head injury in past 3 months Intracranial tumour /vascular abnormality/ aneurysms Active bleeding/ bleeding disorders Peptic ulcer/ esophageal varies H/o major surgery within 3 weeks Uncontrolled hypertension Pregnancy Any wound/ recent fracture/ tooth extraction

38. ANTIFIBRINOLYTIC DRUGS Epsilon amino- caproic acid It is a lysine analogue It combines with lysine binding sites of plasminogen and plasmin , so that plasmin is not able to bind to fibrin and lyse it. It is a specific antidote for fibrinolytic agent and bleeding due to their use Rapid i.v injection results in hypotension,bradycardia and arrthymias

39. Tranexamic acid Like EACA, it binds to the lysine biding site on plasminogen and prevents its combination with fibrin leading to fibrinolysis It is 7 times more potent than EACA Used to control excessive bleeding due to Fibrinolytic drug Cardio-pulmonary bypass surgery Tonsillectomy, prostatic surgery, tooth extraction in heamophilics

40. 4. menorrhagia , due to IUCD 5. Recurrent epistaxis , peptic ulcer Main side effects are nausea, diarrhoea .

41. Thank you