Fibrinolytics

presentation on fibrinolytics

1. FIBRINOLYTICS Presented by SREYA S 1st Semester M Pharm Dept. of pharmacology

2. Fibrinolytic drug , also called  thrombolytic drug , any agent that is capable of stimulating the dissolution of a blood clot (thrombus ) Fibrinolytic drugs work by activating the so-called fibrinolytic pathway . Blood clots can occur in any vascular bed; however, when they occur in coronary, cerebral or pulmonary vessels, they can be immediately life-threatening coronary thrombi are the cause of myocardial infarctions, cerebrovascular thrombi produce strokes, and pulmonary thrombo emboli can lead to respiratory and cardiac failure . Therefore, it is important to rapidly diagnose and treat blood clots.

3. Thrombolytic drugs dissolve blood clots by activating plasminogen , which forms a cleaved product called plasmin . Plasmin is a proteolytic enzyme that is capable of breaking cross-links between fibrin molecules, which provide the structural integrity of blood clots Mechanisms of Thrombolytics

4. Tissue plasminogen activator ( tPA ) Alteplase , Retaplase , Tenecteplase streptokinase (SK ) Streptokinase and anistreplase   urokinase (UK) .  F ibrinolytic drugs

5. This family of thrombolytic drugs is used in acute myocardial infarction, cerebrovascular thrombotic stroke and pulmonary embolism Alteplase is a recombinant form of human tPA.Moderately specific for fibrin bound plasminigen . It has a short half-life (~5 min) and therefore is usually administered as slow iv infusion .non antigenic . dis -Nausea ,mild hypotension Retaplase is a genetically engineered, smaller derivative of recombinant tPA . Longer acting than rtPA . It is usually administered as IV bolus injections. but less specific for fibrin bound plasminogen . It is used for acute myocardial infarction and pulmonary embolism . Dose- 10mg over 10min repeated after 30 min Recombinant Tissue Plasminogen Activators

6. Tenecteplase (TNK- tPA ) has a longer half-life and greater binding affinity for fibrin than rtPA . Because of its longer half-life, it can be administered by IV bolus Single bolus dose 0.5 mg/kg sufficient . Very expensive . It is only approved for use in acute myocardial infarction STEMI Cranial bleeding

7. Streptokinase and anistreplase are used in acute myocardial infarction, arterial and venous thrombosis, and pulmonary embolism. These compounds are antigenic because they are derived from streptococci bacteria. Natural streptokinase (SK) is isolated and purified from streptococci bacteria. Its lack of fibrin specificity makes it a less desirable thrombolytic drug than tPA compounds because it produces more fibrinogenolysis . Anistreplase ( Eminase ®) is a complex of SK and plasminogen . It has more fibrin specificity and has a longer activity than natural SK; however, it causes considerable fibrinogenolysis . Streptokinase

8. Combines with circulating plasminogen forms activator complex proteolysis of plasminogen Active plasmin • Cheap,widely used in India Disadvantages 1 Activates both circulating & fibrin bound plasminogen Depletion of circulating plasminogen → bleeding 2. Antistreptococcal Abs from past infections inactivate considerable fraction of initial dose , loading dose needed 3 Repeat doses less effective due to neutralisation by Abs

9. Uses Acute myocardial infarction – 7.5 to 15 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

10. Urokinase , a protease enzyme that activates plasminogen directly, is obtained from  tissue culture of human kidney cells It has limited clinical use because, like SK, it produces considerable fibrinogenolysis ; however, it is used for pulmonary embolism . One benefit over SK is that UK is non-antigenic ; however, this is offset by a much greater cost Urokinase

11. Rapid acting, more potent Superior in dissolving old clots Short half life 4-8 min Nausea, mild hypotension, fever may occur. For MI : 2.2IU+-

12. Acute myocardial infarction Deep vein thrombosis Pulmonary embolism Peripheral arterial occlusion Ischemic Stroke Uses

13. Intracranial hemorrhage. Head injury/major surgery in past 3 months Intracranial tumors/vascular abnormality/aneurysms Active bleeding/bleeding disorders Peptic ulcer Any wound or recent fracture or tooth extraction Severe Hypertension Contraindications to thrombolytic therapy

14. Antifibrinolytics  are a class of  medicationthat are inhibitors of  fibrinolysis .     Aminocaproic acid  Tranexamic acid. These lysine-like drugs interfere with the formation of the fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators (primarily t-PA and u-PA) which takes place mainly in lysine rich areas on the surface of fibrin . These drugs block the binding sites of the enzymes or  plasminogen  respectively and thus stop  plasmin formation. They are used in  menorrhagia  and bleeding tendency due to various causes ANTIFIBRINOLYTICS

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