Fibrinolytics, also known as thrombolytics, work to dissolve blood clots and are used to treat conditions like heart attacks, deep vein thrombosis, and pulmonary embolism. The main fibrinolytic agents discussed are streptokinase, tissue plasminogen activator (t-PA), and its variants reteplase and tenecteplase. These work by activating plasminogen and converting it to plasmin to break down fibrin clots. Their use comes with risks of hemorrhage, so antifibrinolytic drugs like tranexamic acid and aminocaproic acid are used to reduce bleeding when fibrinolytics are given.

1. FIBRINOLYTICS [THROMBOLYTICS] DR.SOMASHEKARA.S.C DEPARTMENT OF PHARMACOLOGY SVS MEDICAL COLLEGE

2. FIBRINOLYTIC AGENTS 1. Streptokinase, Anistrplase 2. Tissue plasminogen activator (t-PA) Alteplase, Reteplase, Tenecteplase. 3. Urokinase

3. STREPTOKINASE

4. Protein obtained from Group-C ß haemolytic streptococci. No intrinsic enzyme activity. Forms a stable non covalent 1:1 complex with plasminogen. Causes conversion of plasminogen to plasmin. Relatively cheap. STREPTOKINASE STREPTOKINASE Streptokinase Streptokinase

5. Dose: 7.5-15lac IU, 15lac IU/vial MI: 7.5-15lac IU infused over 1hr To be avoided in - patients with recent major streptococcal infection. - Previous treatment by streptokinase because antibodies diminish efficacy. Adverse effects: Bleeding, antigenic, fever, hypotension & arrhythmias Streptokinase

6. Anistreplase Prodrug - Streptokinase-plasminogen complex Slowly hydrolysed releasing streptokinase activated plasminogen which converts endogenous plasminogen to plasmin Long duration of action (1-2hrs)

7. Urokinase Isolated from cultured human kidney cells Indicated in pts in whom streptokinase has been used for an earlier episode Dose: M.I: 2.5lac IU i.v over 10min…. 5lac IU over next 60min Use limited  lacks fibrin specificity, very expensive. Saruplase  selective to fibrin.

8. tissue Plasminogen activator (t-PA)

9. Tissue plasminogen activator (t-PA) Bind to fibrin via lysine binding sites & activates plasminogen several hundred fold more rapidly. Specific to fibrin bound plasminogen ( Half life = 5-10 min) Alteplase (rt-PA)  recombinant DNA technology from human tissue culture Rapidly metabolised by liver ( Half life = 5-10 min) Non antigenic, nausea, mild hypotension, fever, hemorrhage Dose: 50mg vial + 50ml solvent(water) 15mg i.v bolus…50mg over 30min, then 35mg over next 1hr

10. Tissue plasminogen activator (t-PA) Reteplase and tenecteplase are recombinant mutant variants of t-PA Resistant to inhibition by plasma activator inhibitor Have faster onset of action & longer duration of action Similar to t-PA in efficacy and toxicity

11. USES OF FIBRINOLYTICS 1. Acute Myocardial Infarction 2. Deep vein thrombosis 3. Pulmonary Embolism 4. Peripheral vascular disease

12. Hemorrhagic toxicity Major toxicity – hemorrhage because of Lysis of fibrin in physiological thrombi at site of vascular injury Systemic lytic state  systemic formation of plasmin. If heparin used concurrently  bleeding 2-4% intracranial hemorrhage (most serious)

13. Contraindications to thrombolytics Surgery within 10 days. Serious gastrointestinal bleeding within 3 months. History of hypertension (DBP>110mm Hg) Active bleeding or hemorrhagic disorder. Previous cerebrovascular accident. Aortic dissection. Acute pericarditis.

14. Fibrinolytic therapy Initiate within 30 min of presentation (i.e. door -to-needle time 30 min) 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. Fibrinolysis is generally preferred to PCI for patients presenting in the first hour of symptoms of MI..

15. Antifibrinolytic drugs Aminocaproic acid Tranexamic acid Aprotinin

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. ANTIFIBRINOLYTICS USES: 1.Overdose of Fibrinolytic agents 2.To prevent recurrences of subarachnoid & GI hemorrhage 3.Certain traumatic & Surgical bleeding, prostectomy, tooth extraction in hemophiles 4.Abruptio placentae, PPH & certain cases of menorrhagia

18. ANTIFIBRINOLYTICS DISADVANTAGES: 1.In treatment of haematuria it can cause ureteric obstruction by unlysed clots 2.Can cause intravascular thrombosis 3.Rapid i.v - hypotension, bradycardia, arrhythmias 4.Myopathy, careful in renal impaired pts

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