Anticoagulants, Fibrinolytic, Antiplatelet Agent.pptx

PPT

1. Anticoagulants, Fibrinolytic, Antiplatelet Agent Nikhil Bhavsar 20MPH209 Mpharm (pharmacology) IPNU 1

2. HAEMOSTASIS & HOMEOSTASIS: Haemostasis is a process to prevent and stop bleeding, It means to keep a blood within a damaged blood vessels. It is the first stage of wound healing as well as a process in blood clotting. Homeostasis is the ability to maintain a relatively stable internal state that persists despite changes in the world out side. In short that Maintains a normal body environment. 2

3. Clotting Factors: Fibrinogen Prothrombin Thromboplastin or Tissue Factor Calcium (Ca2 +) Proaccelerin -------- Proconvertin Antihaemophilic Factor A Chrishtmas Factor Or Plasma Thromboplastin Component [PTC] Stuart Factor or Thrombokinase Plasma Thromboplastin Antecedent [PTA] Or Antihaemophilic Factor C Hagman Factor Fibrin Stabilising Factor 3

4. Blood clotting cascade: 4

5. COAGULANTS: Coagulants are the agents which stops the bleeding and start clotting. i.g . – Vitamin K Vitamin K is the natural coagulant. Normal clotting depends on adequate amount of vitamin K in the body. It is not involved in in actual clotting process, It is required for the synthesis of four clotting factors from liver cells: Factor 2,7,9,10. 5

6. Vitamin K is a fat soluble vitamin found in liver, leafy vegetables and pulses. 6

7. Deficiency of vitamin K: Manifested as increased bleeding tendency ( i.g . postoperative bleeding and hypoprothrombinaemia . 7

8. ANTICOAGULANTS: Anticoagulants are the agents which stop or decreases the clotting phenomenon. 8

9. Classification: Parenteral Anticoagulants: Heparin Low Molecular Weight Heparin : Enoxaparin, Dalteparin, Reviparin, Tinzaparin Synthetic Heparin Derivatives: Fondaparinux sodium, Idraparinux sodium Direct Thrombin Inhibitors: Hirudin-Based Thrombin Inhibitors: Lepirudin, bivalirudin Synthetic Thrombin Inhibitor: Argatroban. 9

10. Oral Anticoagulants: Direct Thrombin Inhibitor(DTI): Debigatran Direct Factor Xa Inhibitors: Rivaroxiban, Apixaban, Edoxaban Vitamin K Antagonists: Coumarin Derivatives: Warfarin, Dicumarol (rarely used) Indanedione Derivatives: Phenindione, Anisindione (Rarely used). 10

11. Heparin: Heparin is a mixture of sulfated mucopolysacharides with a molecular weight ranging from 10000 – 40000. Commercial preparations are obtained from beef lung and pig intestinal mucosa and standardised after biological assay. 11

12. Mechanism of action: 12

13. Protamine Sulphate is a specific antagonist for Heparin overdose. It is a strongly basic low molecular weight protein which when given I.V. neutralises strongly acidic heparin weight by weight. Neutralisation of LMWH by protamine is incomplete. Protamine cannot antagonise the actions of Fondaparinux. However, the use of excess of protamine sulphate should be avoided, as itself has an anticoagulant effect. 13

14. Low molecular weight Heparin : Drugs: Enoxaparin, Dalteparin, Reviparin, Tinzaparin LMWH inhibit the factor 10. Ranging 2000-9000 molecular weight 14

15. Synthetic Heparin Derivatives: Drugs: Fondaparinux sodium, Idraparinux sodium Fondaparinux Sodium: FS is a synthetic pentasacharide that causes an Antithrombin 3 mediated selective inhibition of factor 10. It is administered S.C. Once daily (usual adult dose is 2.5 mg). 15

16. Bioavailability is almost 100% by this route. It has a lesser antiplatelet action and hence chances of thrombocytopenia are less frequent . It is generally preferred for thrombo prophylaxis of patients undergoing hip or knee surgery and for therapy of pulmonary embolism. 16

17. Vitamin K antagonist: Coumarin Derivatives: Warfarin, Dicumarol(rarely used) Indanedione Derivatives: Phenindione, Anisindione (Rarely used). Warfarin: - Mechanism of action: act by competitively inhibiting vitamin K reductase and therefore inhibit the synthesis of clotting factors 2,7,9,10 by the liver. 17

18. Therapeutic Uses of anticoagulant agent:- Prevention and Treatment of Deep vein Thrombosis and pulmonary embolism . In the treatment of Myocardial Infection and Unstable angina. In the treatment of Rheumatic Heart Disease In the treatment of cerebrovascular Diseases. In the treatment of peripheral (retinal vessels) embolism. During cardiac bypass surgery and In placing artificial heart valves to prevent formation of Thrombus. 18 DEEP VEIN THROMBOSIS PULMONARY EMBOLISM

19. Adverse Effects: Haemorrhage is the commonest adverse effect of parenteral / oral anticoagulant therapy. Heparin: Heparin induced thrombocytopenia. Osteoporosis Hypersensitivity Transient alopecia 19

20. Warfarin: Teratogenic effects. It crosses placenta and can lead to haemorrhagic disorders in foetus and foetal bone deformities Transient alopecia Dermatitis Diarrhoea 20

21. Study of New anticoagulant drug in patients with atrial fibrillation: Purpose: to determine the safety and develop a dosing regimen of an investigational anti coagulant drug (ATI-5923) in patients with atrial fibrillation. Condition or disease Treatment Phase Atrial Fibrillation Drug: ATI-5923 Phase 2 21

22. Atrial Fibrillation: AF is an abnormal heart rhythm(arrhythmia) characterized by rapid and irregular beating of the atrial chamber of the heart. Normal heart rate: 60-100 beats Atrial Fibrillation Heart rate: >100 beats ATI-5923: ATI-5923 ia a structural analog of warfarin that is being developed as an oral anticoagulant. ATI-5923 is a selective, non-competitive inhibitor of vitamin K epoxide reductase. 22

23. Fibrinolytic agent: Fibrinolytic agents is also known as Thrombolytic agent. These drugs are used to dissolve the thrombin(clot) in blood vessels. Drugs: Streptokinase, Urokinase, alteplase, reteplase 23

24. Mechanism of action: 24

25. NO. FEATURE STREPTOKINASE UROKINASE ALTEPLASE 1 Source β– haemolytic Streptococci group C. Enzyme isolated from human urine. By DNA recombinant technology from human tissue culture. 2 Action Activator complex formed with circulatory plasminogen. Activates plasminogen directly. Activates plasminogen in the gel phase. 3 Adverse effect Hypersensitivity, anaphylactic reaction. Fever and hypotension. Nausea and hypotension 4 Uses Acute myocardial infection, deep vein thrombosis, pulmonary embolism. 25

26. Antifibrinolytic Agent: These agent is also known as Antithrombolytic agent. These drugs prevent the blood loss by decrease the Fibrinolytic activity. These are useful in haemophilic patients who may be prone to break through bleeding, after surgery, as the wound is healing. Drugs: Aminocaproic acid, tranexamic acid, A protinin 26

27. Antiplatelet agent: Antiplatelet drugs are known as platelet aggregation inhibitor. These drugs decreases the platelet aggregation and inhibit thrombus formation. 27

28. Classification: Irreversible cox-1 (Cyclooxygenase) inhibitor: Aspirin ADP (Adenosine diphosphate) Blocker: (P 2 Y 12 receptor) Clopidogrel Ticlopidine Ticagrelor PDE-3 (Phosphodiester) Inhibitors: Dipyridamol Cilostazole 28

29. Glycoprotein IIB/IIIA  inhibitors (GP IIB/IIIA): Abciximab Eptifibatide Tirofiban Protease-activated receptor – 1 (PAR-1) antagonist: Vorapaxar 29

30. Mechanism of action: 30

31. Therapeutic Uses: M yocardial infraction: Low dose aspirin or aspirin + Clopidogrel or aspirin + Dipyridamol are used to reduce mortality and to prevent reinfraction. Unstable Angina: Aspirin / clopidogrel can reduce the risk of impending MI and sudden death Coronary-bypass Graft Implants: These are used to maintain the patency of blood vessels during and after CABG. 31

32. Prosthetic H eart valves and arterio-venus shunts: To reduce the formation of emboli / microthrombi on artificial heart valves and to prolong the potency of shunts implanted for haemodialysis. Cerebrovascular Transient Ischaemic attacks: To reduce the incidence of TIAs and to reduce the risk of stroke in patients with TIAs. Aspirin / Clopidogrel or prasugrel their combination can be used. 32

33. Adverse effect: Nausea Excessive bleeding Fever Thrombocytopenia Dyspnea Diarrhoea Abdominal pain 33

34. Reference: Sharma & Sharma’s, Principles of pharmacology, HL Sharma | KK Sharma, Paras Medical Publisher. Review article by Clinical trial.gov https:// clinicaltrials.gov/ct2/show/NCT00431782 34

35. Thank you  35