Antiplatelet, Anticoagulant & Fibrinolytic Therapy

Arterial thrombosis
venous thrombosis

 

ANTIPLATELET, ANTICOAGULANT AND FIBRIN­OLYTIC THERAPY

  • Arterial and venous thrombosis with embolic phenom­enon like deep vein thrombosis, pulmonary embo­lism and other embolizations result in morbidity and death.

Drugs which prevent thromboembolic phenom­enon are:

 

Direct thrombin inhibitors 1
Drugs which prevent thromboembolic phenom enon
  • 1. Drugs which inhibit platelet aggregation
  • 2. Drugs which inhibit thrombin and fibrin genera­tion.

ANTIPLATELET DRUGS

  • These affect cyclooxygenase (COX), adenosine diphos­phate receptors, platelet adhesions, glycoprotein (Gp), and thrombin.
  • Gp lIb j IIIa on platelet surface is the final common pathway for platelet activation. Therefore, inhibiting this results in anticoagulation.

Aspirin

  • It causes COX inhibition and prevention of thrombox­ane A2 synthesis, leading to decreased platelet acti­vation and aggregation. The effect of aspirin occurs within 1 hour and lasts for 1 week. Dose is 75-325 mgjday.

Thienopyridines

  • Ticlopidine and Clopidogrel inhibit ADP-induced plate­let aggregation.
  • The CAPRIE trial on these drugs demonstrated re­duction in ischemic events in patients with MI and peripheral arterial disease.

Gp lIb / IlIa antagonists

  • These are disintegrins which suppress fibrinogen e.g. Abciximab, Tirofiban.
  • They are widely used in coronary artery disease.

ANTICOAGULANT DRUGS Heparin

  • Unfractionated heparin (UFH) molecules bind to anti­thrombin potentiating its action and inactivating fac­tor Xa and thrombin.
  • This prevents and treats thrombosis in patients. Unfractionated heparin can be given IV or subcuta­neously.
  • It requires monitoring of aPTI – activated partial thromboplastin time.
  • Antidote is protamine sulphate.

Low molecular weight heparin

  • These are derived from cleavage of unfractionated heparin into low molecular weight compounds.
  • They have more of anti-factor Xa but less of anti­thrombin activity.
  • They are safer for use in patients of unstable angina, MI (myocardial infarction), DVT(deep vein thrombo­sis). Lab monitoring is not required.
  • Examples are dalteparin, enoxaparin etc.

Heparinoids

  • Act as anticoagulant by activating heparin co-factor – II. Only used if heparin causes thrombocytopenia.

Pentasaccharides

  • Once weekly dose may be given for primary or sec­ondary prevention of thromboembolic phenomenon.

Direct thrombin inhibitors

Direct thrombin inhibitors 2
Direct thrombin inhibitors

Argatroban, LepirudinWarfarin

  • It inhibits vitamin K reductase and prothrombin. It is not used in pregnancy.
  • During Warfarin therapy PT – prothrombin time and INR are measured.
  • INR of 2-3 is recommended.
  • In prosthetic valves INR of 2.5 to 3.5 is recommended. INR is patients PT( prothrombin time) divided by the mean PT.

FIBRINOLYTIC DRUGS STREPTOKINESE

  • This is obtained from beta hemolytic streptococci cul­tures.
  • It is antigenic and can even cause anaphylaxis.
  • It is used in MI and DVT (deep vein thrombosis) to lyse the clots.

UROKINASE

  • It is obtained from human fetal kidney cell cultures or recombinant urokinase from mammalian tissue cultures.
  • Tissue type plasminogen activator (RTPA) Recombinant tissue type plasminogen activator is used to treat DVT, pulmonary embolism, acute MI and acute strokes. 

Indications for Anticoagulation

  • That’s the short description about thrombosis, anticoagulant treatment, etc.· DVT – antocoagulants for 6 wks to 6 months
  • · Pulmonary embolism – 6 months
  • · Prosthetic heart valves – lifelong
  • · MI – for variable duration

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