Fibrinolytic agents

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Fibrinolytic agents

  1. 1. FIBRINOLYTICS [THROMBOLYTICS] DR.SOMASHEKARA.S.C DEPARTMENT OF PHARMACOLOGY SVS MEDICAL COLLEGE
  2. 2. FIBRINOLYTIC AGENTS 1. Streptokinase, Anistrplase 2. Tissue plasminogen activator (t-PA) Alteplase, Reteplase, Tenecteplase. 3. Urokinase
  3. 3. STREPTOKINASE
  4. 4. <ul><li>Protein obtained from Group-C ß haemolytic streptococci. </li></ul><ul><li>No intrinsic enzyme activity. </li></ul><ul><li>Forms a stable non covalent 1:1 complex with plasminogen. </li></ul><ul><li>Causes conversion of plasminogen to plasmin. </li></ul><ul><li>Relatively cheap. </li></ul>STREPTOKINASE STREPTOKINASE Streptokinase Streptokinase
  5. 5. <ul><li>Dose: 7.5-15lac IU, 15lac IU/vial </li></ul><ul><li>MI: 7.5-15lac IU infused over 1hr </li></ul><ul><li>To be avoided in </li></ul><ul><li>- patients with recent major streptococcal infection. </li></ul><ul><li>- Previous treatment by streptokinase because </li></ul><ul><li>antibodies diminish efficacy. </li></ul><ul><li>Adverse effects: </li></ul><ul><li>Bleeding, antigenic, fever, hypotension & arrhythmias </li></ul>Streptokinase
  6. 6. Anistreplase <ul><li>Prodrug - Streptokinase-plasminogen complex </li></ul><ul><li>Slowly hydrolysed releasing streptokinase activated plasminogen which converts endogenous plasminogen to plasmin </li></ul><ul><li>Long duration of action (1-2hrs) </li></ul>
  7. 7. Urokinase <ul><li>Isolated from cultured human kidney cells </li></ul><ul><li>Indicated in pts in whom streptokinase has been used for an earlier episode </li></ul><ul><li>Dose: M.I: 2.5lac IU i.v over 10min…. </li></ul><ul><li>5lac IU over next 60min </li></ul><ul><li>Use limited  lacks fibrin specificity, very expensive. </li></ul><ul><li>Saruplase  selective to fibrin. </li></ul>
  8. 8. tissue Plasminogen activator (t-PA)
  9. 9. Tissue plasminogen activator (t-PA) <ul><li>Bind to fibrin via lysine binding sites & activates plasminogen several hundred fold more rapidly. </li></ul><ul><li>Specific to fibrin bound plasminogen ( Half life = 5-10 min) </li></ul><ul><li>Alteplase (rt-PA)  recombinant DNA technology from human tissue culture </li></ul><ul><li>Rapidly metabolised by liver ( Half life = 5-10 min) </li></ul><ul><li>Non antigenic, nausea, mild hypotension, fever, hemorrhage </li></ul><ul><li>Dose: 50mg vial + 50ml solvent(water) </li></ul><ul><li>15mg i.v bolus…50mg over 30min, then 35mg over next 1hr </li></ul>
  10. 10. Tissue plasminogen activator (t-PA) <ul><li>Reteplase and tenecteplase are recombinant mutant variants of t-PA </li></ul><ul><li>Resistant to inhibition by plasma activator inhibitor </li></ul><ul><li>Have faster onset of action & longer duration of action </li></ul><ul><li>Similar to t-PA in efficacy and toxicity </li></ul>
  11. 11. USES OF FIBRINOLYTICS <ul><li>1. Acute Myocardial Infarction </li></ul><ul><li>2. Deep vein thrombosis </li></ul><ul><li>3. Pulmonary Embolism </li></ul><ul><li>4. Peripheral vascular disease </li></ul>
  12. 12. Hemorrhagic toxicity <ul><li>Major toxicity – hemorrhage because of </li></ul><ul><li>Lysis of fibrin in physiological thrombi at site of vascular injury </li></ul><ul><li>Systemic lytic state  systemic formation of plasmin. </li></ul>If heparin used concurrently  bleeding 2-4% intracranial hemorrhage (most serious)
  13. 13. Contraindications to thrombolytics <ul><li>Surgery within 10 days. </li></ul><ul><li>Serious gastrointestinal bleeding within 3 months. </li></ul><ul><li>History of hypertension (DBP>110mm Hg) </li></ul><ul><li>Active bleeding or hemorrhagic disorder. </li></ul><ul><li>Previous cerebrovascular accident. </li></ul><ul><li>Aortic dissection. </li></ul><ul><li>Acute pericarditis. </li></ul>
  14. 14. Fibrinolytic therapy <ul><li>Initiate within 30 min of presentation </li></ul><ul><li>(i.e. door -to-needle time 30 min) </li></ul><ul><li>Reduces the relative risk of in-hospital death by up to 50% when administered within the first hour of the onset of symptoms of STEMI. </li></ul><ul><li>Fibrinolysis is generally preferred to PCI for patients presenting in the first hour of symptoms of MI.. </li></ul>
  15. 15. Antifibrinolytic drugs Aminocaproic acid Tranexamic acid Aprotinin
  16. 16. Epsilon Aminocaproic acid Lysine analog MOA: acts by combining with lysine binding sites of plasminogen & plasmin, and prevents the binding of these to fibrin – prevents its lysis Specific antidote for fibrinolytic agents Dose: Initial priming dose 5gm oral/i.v…. 1g hrly till bleeding stops(max.30g in 24hrs)
  17. 17. ANTIFIBRINOLYTICS <ul><li>USES: </li></ul><ul><li>1.Overdose of Fibrinolytic agents </li></ul><ul><li>2.To prevent recurrences of subarachnoid & GI hemorrhage </li></ul><ul><li>3.Certain traumatic & Surgical bleeding, prostectomy, </li></ul><ul><li>tooth extraction in hemophiles </li></ul><ul><li>4.Abruptio placentae, PPH & certain cases of menorrhagia </li></ul>
  18. 18. ANTIFIBRINOLYTICS <ul><li>DISADVANTAGES: </li></ul><ul><li>1.In treatment of haematuria it can cause ureteric obstruction </li></ul><ul><li>by unlysed clots </li></ul><ul><li>2.Can cause intravascular thrombosis </li></ul><ul><li>3.Rapid i.v - hypotension, bradycardia, arrhythmias </li></ul><ul><li>4.Myopathy, careful in renal impaired pts </li></ul>
  19. 19. Thank you

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