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Thrombolytics or Fibrinolytics

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Thrombolytics or Fibrinolytics

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Thrombolytics or Fibrinolytics

  1. 1. Thrombolytics or Fibrinolytics Dr. Lokendra Sharma Professor SMS Medical College, Jaipur Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  2. 2. Definition • Thrombolytics are the drugs used to lyse clot to recanalize occluded blood vessels( mainly coronary artery). • They act by activating natural fibrinolytic system. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  3. 3. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  4. 4. Thrombolytic drugs – mechanism of action Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  5. 5. Thrombolytic drugs – mechanism of action Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  6. 6. Thrombolytic drugs – mechanism of action Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  7. 7. Thrombolytic drugs – mechanism of action Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  8. 8. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  9. 9. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  10. 10. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  11. 11. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  12. 12. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  13. 13. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  14. 14. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  15. 15. Streptokinase • Plasma half life: t1/2 40-80 min. • The streptokinase-plasminogen complex is not inhibited by natural alpha 2- antiplasmin. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  16. 16. Streptokinase…. Therapeutic uses:  Acute myocardial infarction  Acute pulmonary embolism  Deep-vein thrombosis  Arterial thrombosis [PVD]  Route I.V. Adverse Effects:  Hemorrhage- most serious cerebral hemorrhage.  Allergic reactions – rarely anaphylaxis and fever Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  17. 17. Urokinase • Isolated from human • Directly acts on plasminogen • Non-antigenic • Adverse action profile same as Streptokinase. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  18. 18. Alteplase • Alteplase (tPA)originally derived from cultured human melanoma cells-now recombinant DNA technology. • Mechanism of action : It has low affinity for free plasminogen in the plasma-rapidly activates plasminogen that is bound to fibrin in a thrombus or a hemostatic plug. • Fibrin selective: At low doses, it has the advantage of lysing only fibrin, without unwanted degradation of other proteins- fibrinogen. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  19. 19. Reteplase & Tenectaplase • It is fibrin-specific human t-PA prepared by recombinant mutation technology. • It has longer duration than alteplase. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  20. 20. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  21. 21. Anistreplase • Anisoylated plasminogen activator complex. • Anistreplase is a preformed complex of streptokinase and plasminogen and it is considered to be a prodrug. Advantages: Rapid IV injection may be given Greater clot selectivity. More thrombolytic activity. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  22. 22. Fibrinolytics- Indications • Acute MI • Acute Ischemic Stroke • Deep Vein Thrombosis • Pulmonary embolism • Peripheral arterial occlusion • Administration STEMI • Within 1 hr[golden rule] Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  23. 23. Thrombolytic therapy benefit • Clinical trials have firmly established the benefit of thrombolytic therapy for patients with acute MI with ST-segment elevation within 12 hours of symptom onset. • Unstable angina or MI without ST elevation do not get benefit. • Rapid initiation of thrombolytic therapy is essential to optimize patient outcome because each additional hour of delay from symptom onset to treatment corresponds to a 0.5% to 1% increase in mortality. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  24. 24. USES of fibrinolytics 1. ACUTE MYOCARDIAL INFARCTION Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  25. 25. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  26. 26. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  27. 27. 2. Deep vein thrombosis 3. Pulmonary embolism Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  28. 28. Procedures for Deep vein thrombosis Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  29. 29. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  30. 30. 4.Peripheral arterial occlusion 5. Acute Ischemic Stroke Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  31. 31. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  32. 32. Fibrinolytics - CI • Absolute Contraindications a) Prior ICH b) Known cerebral vascular lesion c) IC malignant neoplasm d) Ischemic stroke-past 3 months e) Aortic dissection f) Active bleeding, bleeding diathesis [not menses] g) Closed head injury/ facial trauma – past 3 months • Relative Contraindications a) Poorly controlled/ severe HTN b) Major surgery- 3 weeks c) Recent internal bleeding d) SK/Anistreplase –h/o allergy/prior admin. e) Pregnancy f) Active peptic ulcer Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  33. 33. Antidote for overdose of fibrinolytic agents Εpsilon aminocaproic acid(EACA) and Tranexamic acid Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  34. 34. Antifibrinolytics As implied by the name, these agents enhance hemostasis when fibrinolysis contributes to bleeding • ε-aminocaproic acid (EACA) • Tranexamic acid (TXA) Lysine analogues Aprotinin: Approved by FDA to reduce blood loss and transfusion in coronary artery bypass graft surgery (CABG) but marketing suspended 11/5/07 Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  35. 35. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  36. 36. Lysine analogues: EACA and TXA Indicated for enhancing hemostasis when fibrinolysis contributes to bleeding Both competitively inhibit plasmin binding to fibrin Widely used in cardiac surgery, but data supporting safety and efficacy are limited EACA associated with increased incidence of certain neurologic deficits; concerns about rhabdomyolysis and renal dysfunction Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  37. 37. BLOOD & PLASMA VOLUME EXPANDERS Plasma expanders are agents that have relatively high molecular weight and boost the plasma volume by increasing the osmotic pressure. They are used to treat patients who have suffered hemorrhage or shock. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  38. 38. VOLUME EXPANDERS Contd… Volume expanders are the i.v., fluid solutions that are used to increase or retain the volume of fluid in the circulating blood . Generally volume expanders are used to replace fluids that are lost due to illness, trauma , surgery, burns & extensive tissue damage These are used to correct hypovolemia due to loss of plasma or blood . Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  39. 39. TYPES OF VOLUME EXPANDERS :- 1.Crystalloids: Crystalloids are aqueous solutions of mineral salts or other water soluble molecules. E.g, normal saline ,dextrose , ringers solution etc. 2.Colloids: colloids are larger insoluble molecules , such as dextran , human albumin, gelatin, blood. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  40. 40. WHAT DO THEY DO?? Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  41. 41. IDEAL PROPERTIES OF PLASMA VOLUME EXPANDERS 1 • Iso-oncotic with plasma • Distributed to i.v., compartement only 2 • Pharmacodynamically inert • Non-pyrogenic, non-allergic &non-antigenic 3 • No interference with blood grouping or cross matching • Stable, easily sterlizable and cheap. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  42. 42. SOME VOLUME EXPANDERS : Human albumin Dextran DX40 DX70 Polygeline Hetastarch Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  43. 43. MECHANISM OF ACTION: Generally works on the principle of osmosis. Increases plasma osmotic pressure, drawing water into plasma from intestinal fluid . Since the lost blood is replaced with a suitable fluid, the diluted blood flows more easily, even in small vessels. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  44. 44. SOME CRYSTALLOIDS: Normal saline Lactate ringer’s solution Dextrose solution Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  45. 45. USES OF PLASMA EXPANDERS: •Used in conditions where blood or plasma has been lost or has moved to extra vascular compartments e.g. burns , hypovolaemic shock, severe trauma, endotoxin shock and extensive tissue damage. •Can also be used as a temperory measure in cases of whole blood loss till the same can be arranged. NOTE: They do not have any oxygen carrying capacity. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  46. 46. CONTRADICTIONS TO PLASMA EXPANDERS: Allergy Heart failure Severe anemia Thrombocytopenia Pulmonary edema Renal insufficiencyDr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  47. 47. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur
  48. 48. Dr. Lokendra Sharma, Professor, Department of Pharmacology, S.M.S. Medical College, Jaipur

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