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Anticoagulantsand its uses and dddd.pptx
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- 2. Learning objectives • Toknow the clotting pathways and where they can be intervened. • To know about anticoagulants; heparin and warfarin. • Their mechanism of action. • Common uses and contraindications.
- 3. Coagulation pathways ⦿Two majorpathways ⚫Intrinsic pathway ⚫Extrinsic pathway ⦿ Both converge at a common point ⦿ 13 soluble factors are involved in clotting
- 4. Intrinsic Pathway ⦿ Allclotting factors are within the blood vessels ⦿ Clotting slower ⦿ Activated partial thromboplastin test (aPTT) Extrinsic Pathway ⦿ Initiating factor is outside the blood vessels - tissue factor ⦿ Clotting - faster - in Seconds ⦿ Prothrombin test (PT)
- 5. Blood Vessel Injury IXIXa XI XIa X Xa XII XIIa Tissue Factor Thromboplastin VIIa VII X Prothrombin Thrombin Fibrinogen Fribrin monomer Fibrin polymer XIII Extrinsic Pathway Tissue Injury Intrinsic Pathway Factors affected By Heparin Vit. K dependent Factors Affected by Oral Anticoagulants
- 6. Anticoagulant drugs totreat thromboembolism Drug Class Anticoagulant Parenteral Prototype Heparin Action Inactivation of clotting Factors Effect Prevent venous Thrombosis Anticoagulant Oral Warfarin Decrease synthesis of Clotting factors Prevent venous Thrombosis Antiplatelet drugs Aspirin Decrease platelet aggregation Prevent arterial Thrombosis Thrombolytic Drugs Streptokinase Fibinolysis Breakdown of thrombi
- 7. Uses of anticoagulants •Treatment and Prevention of Deep Venous Thrombosis • Pulmonary Emboli • Prevention of stroke in patients with atrial fibrillation, • artificial heart valves, cardiac thrombus. • During procedures such as cardiac catheterisation and apheresis. • Arterial and venous thrombosis • Pulmonary embolism • Patency of IV cannulae and shunts in dialysis cases
- 8. Contra indications • Stroke •Major surgery • Brain neoplasm • Active bleed
- 9. Classification : •Indirect-acting: thecoumarin derevatives drugs (e.g. warfarin) take about 72 h to become fully effective, act for several days, are given orally or by injec.. •Direct-acting: heparin and LMW heparin are rapidly effective, and available parenterally.
- 10. Direct-Acting Anticoagulants: Heparin Mechanism ofaction • naturally-occurring anticoagulant produced by basophils and mast cells. • binds to the enzyme inhibitor antithrombin III (AT), causing a conformational change that results in its activation • The activated AT then inactivates thrombin, factor Xa and other proteases
- 11. Administration • given parenterally •intramuscular injections are avoided because of the potential for forming hematomas • short biologic half-life of about one hour, heparin must be given frequently or as a continuous infusion. • 30% bio-availability after subcutaneous injection as compared to UFH where its is 70-90% .
- 12. Monitoring Of Heparin ActivatedPartial Thromboplastin Time (APTT) Normal range: 25-40 seconds indicator measuring the efficacy of the "intrinsic“ pathway.
- 13. Low Molecular weightHeparins • Are as effective and safe as conventional (unfractionated) heparin at preventing venous thrombosis. • They are eliminated mainly by renal excretion, and unfractionated heparin is preferred in renal failure. • Examples: • enoxaparin, dalteparin, and tinzaparin
- 14. LMWHs Cont…. • Low-molecular-weightheparins are given subcutaneously. • They have a longer half-life than unfractionated heparin, so the effects are more predictable and dosing less frequent (once or twice a day). • LMWHs do not prolong the APTT; • unlike unfractionated heparin, the effect of a standard dose is sufficiently predictable that monitoring is not required routinely. • 90% bio-availability after subcutaneous injection
- 15. Advantages of LMWHs •Better S/C bioavailability as compared to UFH • Since aPTT / clotting times not prolonged hence clinical monitoring not required . • Much lesser risk of osteoporosis which is associated with long-term use of UFH
- 16. Warfarin • synthetic derivativeof coumarin, • it is a Vitamin K antagonist. • it is readily absorbed from the GIT and more than 90% bound to plasma protein.
- 17. Warfarin Conti…. Mechanism ofaction • Inhibits epoxide reductase enzyme • Interfere with active hydroquinone form of Vitamin-K • Which acts as cofactor for enzyme Gama-Carboxylase • Thus prevents carboxylation of vitamin-k dependent clotting factors like:II, VII, IX and X
- 18. Administration • Warfarin isavailable orally. • Warfarin has a long half-life and need only be given once a day • It takes several days for warfarin to reach the therapeutic effect
- 19. Onset of actionof warfarin The effect takes several days to develop because of the time taken for degradation of preformed carboxylated clotting factors. The onset of action thus depends on the elimination half-lives of the relevant factors. Factor VII, with a half-life of 6 hours, is affected first, then IX, X and II, with half-lives of 24, 40 and 60 hours, respectively
- 20. Dosage of warfarin The usual dose to initiate therapy is 5-10 mg daily for 2 days, with the maintenance dose then adjusted according to the INR. 1. INR 2.0-2.5 Prophylaxis of deep vein thrombosis 2. INR 2.0-3.0 treatment of DVT & pulmonary embolism. 3. INR 3.0-4.5 recurrent DVT & pulmonary embolism . • Measure baseline INR prior to starting therapy. • Initial dose of warfarin is usually between 2 to 5 mg once daily and maintenance doses range from 2 to 10 mg once daily. • Consider smaller starting doses for high risk patients (elderly, low body weight, abnormal liver function or at a high bleeding risk).
- 21. Monitoring of Warfarintherapy: • MONITORING OF ANTICOAGULANT THERAPY is by INR ( international normalized ratio ), • which is the ratio of prothrombin time in the patient to that in a normal (un-anticoagulated) person. INR Equation
- 22. Warfarin: Dosing &Monitoring Start low Initiate 5 mg daily Educate patient Stabilise Titrate to appropriate INR Monitor INR frequently (daily then weekly) Adjust as necessary Monitor INR regularly (every 1–4 weeks) and adjust
- 23. The “Ideal” OralAnticoagulant • Once daily dosing • Minimal monitoring required • Reversal agent available • Wide therapeutic index • Low cost • Easy dose adjustments for renal function and age
- 24. Clinical Lab RecommendationsPrior to and During Oral Anticoagulant Therapy .. Warfarin DOACs • CBC (complete blood count) • PT (prothrombin time) • INR (international normalized ratio) NOTE: Initial INR should not be performed using patient self-testing (PST) devices. • CBC • Serum creatinine • Liver function tests (if history or risk of hepatic insufficiency)
- 25. Surgery in patientsreceiving anticoagulant therapy • For elective surgery warfarin may be withdrawn about 5 days before the operation and resumed about 3 days after if condition seems appropriate, low-dose heparin may be used in the intervening period. • In patients with mechanical prosthetic valves, heparin is substituted at full dosage 4 days before surgery and restarted 12-14h after the operation. • Warfarin is restarted when the patient resumes oral intake.
- 26. The use ofanticoagulants in pregnancy • Women on long term warfarin should be advised not to become pregnant while taking the drug. • Heparin should be substituted prior to conception and continued through the first trimester, after which warfarin should replace heparin, as continued exposure to heparin may cause osteoporosis. • Warfarin should be discontinued near term as it exacerbates neonatal hypoprothrombinaemia .
- 27. Why do weneed new anticoagulation drugs? • Heparin-induced thrombocytopenia • Heparin prophylaxis is imperfect • Heparin-associated osteoporosis • Warfarin takes several days for its effect • Warfarin is not as effective in some situations e.g antiphospholipid syndrome • Warfarin interacts with many other drugs • Warfarin is dangerous if not monitored
- 28. Conclusion • Anticoagulant therapyis use extensively. • Current mainstays of treatment are heparin or heparin-like drugs and oral warfarin. • Both have problems but when monitored closely are generally safe. • New anticoagulation drugs are arriving and in particular ximelagatran may revolutionise oral anticoagulation therapy
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