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Anti - Coagulants agents

Anti - Coagulants agents

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Anti - Coagulants agents

  1. 1.  The coagulation process that leads to hemostasis involves a complex set of reactions involving approximately 30 different proteins  These reactions convert fibrinogen, a soluble protein, to insoluble strands of fibrin, which, together with platelets, forms a stable thrombus
  2. 2. Extrinsic pathway Intrinsic pathway
  3. 3.  Direct thrombin inhibitor: (argatroban, bivalirudin, dabigatran etexilate, desirudin)  Factor Xa inhibitor: (apixaban, betrixaban, edoxaban, rivaroxaban, fondaparinux) ** Direct oral anticoagulant ( DOAC): (apixaban, edoxaban, rivaroxaban, dabigatran)  Vitamin K antagonist: (warfarin)  Heparin  LMWH: (dalteparin, enoxaparin, tinzaparin)
  4. 4.  Thrombin (factor lla) : final enzyme in the clotting cascade that cleaves fibrinogen to fibrin and activates factor V,VIII,XI.  Direct thrombin inhibitors are able to block the action of both circulating and clot-bound forms of thrombin because their site of binding to thrombin is not masked by fibrin ( not obstructed), they prevent thrombin from cleaving fibrinogen to fibrin.  Parenteral DTIs include bivalirudin, argatroban, desirudin  The only oral DTI available for clinical use is dabigatran
  5. 5. Drug Uses Monitoring Bivalirudin PCI, HIT, NSTEMI = (aPTT), with a target of 1.5 to 2.5 times the normal range Argatroban PCI, HIT aPTT (target 1.5 to 3 times the initial baseline, not >100 s) . Desirudin DVT prophylaxis aPTT
  6. 6. Drug C/I side effect Antidote Bivalirudin Major bleeding. Bacterial endocarditis severe uncontrolled HTN, diabetic or hemorrhagic retinopathy. Need renal dose adjusment Bleeding, hypotension Argatroban Major bleeding Need kiver dose adjustment Bleeding Genitourinary tract hemorrhage Desirudin Major bleeding Need renal dose adjustment Bleeding, deep vain thrombophlebitis,
  7. 7. Dabigatran is the only oral direct thrombin inhibitor available for clinical use. Additional agents are under development
  8. 8. Monitoring Warning C/I S.E antidote: (aPTT), creatinine if renal insufficiency *risk of thrombotic events following premature discontinuation avoidance of dabigatran in individuals with creatinine clearance <15 mL/minute or in those who are hemodialysis dependent dyspepsia, bleeding Idarucizumab Uses the prevention and management of (VTE) disease, and in stroke prevention in patients with (AF)
  9. 9.  Factor Xa upstream thrombin in clotting cascade at the convergence point of the intrinsic and extrinsic pathway  Direct factor Xa inhibitors are able to block the action of both circulating and clot-bound forms of factor Xa  whereas indirect factor Xa inhibitors such as heparin and fondaparinux are only able to inactivate factor Xa in the fluid phase via antithrombin
  10. 10.  they prevent factor Xa from cleaving prothrombin to thrombin. They bind directly to factor Xa  No parenteral direct factor Xa inhibitors in clinical use  Several oral agents are available, including rivaroxaban, apixaban, edoxaban, betrixaban
  11. 11. Drug Uses Monitoring Rivaroxaban used in the prevention and treatment of (VTE) disease, and in stroke prevention in patients with atrial fibrillation (AF). prior to initiating: CBC, platelet count, (PT), (aPTT),(INR) Apixaban same prior to initiating : CBC, renal function Platelet count, PT, aPTT Edoxaban same Prior to initiation: CBC, renal function Betrixaban prevention of VTE in hospitalized adult medical patients Prior to initiation: renal function
  12. 12. Drug C/I S.E Antidote Rivaroxaban patients with prosthetic heart valves or during pregnancy bleeding , dizziness, insomnia anxiety, depression , fatigue, syncope , wound secretion, abdominal pain Andexanet alfa Apixaban Same Bleeding increased gammaglutamyl trasferase , neausea Andexanet alfa Edoxaban Same Bleeding, GI bleeding,vaginal hemorrhage Andexanet alfa
  13. 13.  Fondaparinux , Heparin, LMWH  Fondaparinux MOA: Potentiates the antithrombin effect that inhibit Xa. Adm.: IV,SC
  14. 14. Uses Monitoring C/I Adverse effects Antidote ACS, VTE treatment & prophylaxis, HIT, superfic ial vein thrombosis PT, aPTT CrCl<30ml/ min, bleeding, bacterial endocarditis Bleeding, anemia, hypotension, *Andexanet alfa
  15. 15. *Heparin:  MOA: accelerate interaction of antithrombin III with both thrombin and factor Xa.  Adm.: IV, SC *LMWH:(enoxaparin,tinzaparin)  MOA: accelerate interaction of antithrombin with factor Xa.  Adm.: SC, IV in acute MI.
  16. 16. Uses Monitoring Anticoagulation ,in PCI, interstitial cystitis, mechanical prosthetic valve, STEMI, NSTEMI, VTE therapeutic aPTT 1-aPTT of 1.5 to 2.5 times Warning C/I S.E Antidote hyperkalemia, thrombocytopenia (HIT), thrombocytopenia, HIT, uncontrolled active bleeding thrombocytopenia (HIT) protamine sulfate
  17. 17. Drug Uses Monitoring Enoxaparin DVT prophylaxis, DVT,PE treatment, PCI, NSTEMI, unstable angina. initial :(PT) and (aPTT), anti Xa level Tinzaparin DVT,PE treatment ,mechanical prosthetic heart valve to bridge anticoagulant, initial :(PT) and (aPTT) anti Xa level
  18. 18. Drug Warning C/I S.E Antidote Enoxaparin ]hyperkalemia, thrombocytopenia, Hypersensitivity to enoxaparin or heparin, history of HIT in the past 100days, active major bleeding Need renal dose adjustment Anemia, hemorrhage, peripheral edema, confusion 1 mg protamine per 1 mg of enoxaparin. Tinzaparin hyperkalemia, thrombocytopenia Hypersensitivity to it or other LMWH or heparin, active bleeding, History of HIT, endocarditis, severe uncontrolled pressure, Spinal/epidural anesthesia Increase ALT, hematoma at injection site, chest pain 1 mg protamine per 100 anti- factor Xa units of LMW heparin.
  19. 19.  Warfarin MOA: inhibit vit K epoxide reductase
  20. 20. Drug Uses Monitoring Warfarin Atrial fibrillation,Acute coronary syndrome,Heart failure,Prosthetic heart valve,Stroke,Deep vein thrombosis ,Pulmonary embolism, Antiphospholipid syndrome INR
  21. 21. Drug C/I S.E Antidote Warfarin Hypersensitivity to warfarin or any component of formulation, hemorrhagic, recent or potential surgery of the eye or CNS, major regional lumbar block anesthesia, pericardial effusion, malignant HTN, bacterial endocarditis, eclampsia, preeclampsia, pregnancy Hemorrhage, ,systemic cholestrol micro-embolism. Vit. K
  22. 22.  LMWH (preferred)  UFH  Alternatives: fondaparinux, danaparoid, argatroban

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