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Drugs affecting thrombosis

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Drugs affecting thrombosis

  1. 1. Drugs affecting Thrombosis 1
  2. 2. 2
  3. 3. Fibrinolytics / thrombolytics • Drugs : – – – – Streptokinase Urokinase Antistreplase Tissue plasminogen activators (t-PA) • Human t-PA (Alteplase) • Reteplase • Tenecteplase
  4. 4. Streptokinase • It is a streptococcal exotoxin ( beta hemolytic streptococci group C) MECHANISM OF ACTION: – It combines with circulating–plasminogen-liberating plasmin which breaks down fibrin – No intrinsic enzymatic activity but forms a stable complex with plasminogen . This complex then converts uncomplexed plasminogen to active plasmin which causes hydrolysis of fibrin plugs . – Plasmin catalyses degradation of fibrinogen as well as clotting factors
  5. 5. USES – Pulmonary embolism – Peripheral arterial occlusion ( given intraarterially) – Venous thrombosis – Lysis of coronary thrombosis(present use) in acute myocardial infarction – Clear occluded arterio venous cannula 5
  6. 6. • ADVERSE EFFECTS – – – – – – Bleeding particularly at the sites of recent trauma. Hypersensitive reactions Anaphylaxis(especially when used second time in a patient) Fever Hypotension Arrhythmias. • PRECAUTIONS – It should not be used if patient has had previous streptokinase therapy within the last 12 months – Blood pressure should be monitored.
  7. 7. Dose - Acute myocardial infarction and pulmonary embolism: - IV infusion loading dose : 250,000 units followed by 100,000 units/hour for 24-72 hours - this may be preceded by chlorpheniramine 10mg and hydrocortisone 100mg to reduce allergic reactions. This is combined with 300mg aspirin ,which should be chewed before swallowing and followed by 150mg daily. 7
  8. 8. CONTRAINDICATIONS – Surgery within 10 days including : • Organ biopsy • Serious trauma – Serious GIT bleeding within 3 months – History of hypertension – Hemorrhagic disorders – Cerebrovascular accident
  9. 9. FIBRINOLYTIC INHIBITORS: • • • • Aminocaproic acid Tranexamic acid Phytomenadione Aprotinin
  10. 10. Aminocaproic acid (EACA) • chemically similar to the amino acid lysine • It competitively inhibits plasminogen activation • rapidly absorbed orally and is cleared from the body by the kidney. • usual oral dosage :6 g four times a day. • When administered intravenously, a 5 g loading dose should be infused over 30 minutes to avoid hypotension. 10
  11. 11. Tranexamic acid • analog of aminocaproic acid • administered orally with a 15 mg/kg loading dose followed by 30 mg/kg every 6 hours 11
  12. 12. Uses of antifibrinolytic drugs • Adjunctive therapy in hemophilia • Bleeding from fibrinolytic therapy • Prophylaxis for rebleeding from intracranial aneurisms • Post-surgical bleeding 12
  13. 13. Adverse effects • EACA – – – – – Intravascular thrombosis Hypotension Bradycardia Arrhythmia Rarely myopathy • Tranexamic acid – – – – Nausea Diarrhoea Headache Thrombophlebitis 13
  14. 14. Contraindication • Disseminated intravascular coagulation • Genitourinary bleeding of upper tract 14
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