Anticoagulants PPT- MBBS -Pharmacology class

Pharmacology class for second MBBS STUDENTS

1. anticoagulants Dr. Ravi Mundugaru Assistant Professor Dept. of Pharmacology AIMS, BG Nagar

2. Classification of In vivo anticoagulants Parenteral anticoagulants Heparin Low molecular weight heparin Heparinoids Direct thrombin inhibitor Enoxaparin Dalteparin Tinzaparin Ardeparin Fondaparinix Heparan sulfate Danaparoid Lepirudin Bivalirudin Argatroban

3. Oral anticoagulants Coumarin derivatives Indandione derivatives Direct factor Xa inhibitor Oral direct thrombin inhibitor Dicumarol Warfarin phenindione Rivaroxaban Apixaban Dabigatran etexilate

4. Used in vitro: Heparin Sodium citrate Sodium oxalate Sodium edetate

5. XIIa , Xia,Kallikrein , Ca2+ Activated by contact Slow Rapid

6. Intrinsic system Extrinsic system VII X The coagulation cascade XII a* XI XI a* IX IX a* X X a* VII a PROTHROMBIN (II) THROMBIN* (II a) FIBRINOGEN FIBRIN (soluble) FIBRIN (insoluble) SLOW RAPID Activated by contact Ca Ca Ca Ca XIII a* Thrombin

7. Heparin Mol.wt 10000 to 20000 Strong electronegative compound, strongest organic acid in body Commercially, obtained from cow lung & pig intestinal mucosa

8. Prothrombin Thrombin Xa Low conc. of Heparin

9. 2. Antiplatelet At higher dose, inhibits platelet aggregation & prolong bleeding time 3. Lipaemia clearing Heparin reduce blood lipid level by releasing lipoprotein lipase from vessel wall & tissues

10. Heparin - Pharmacokinetics Not absorbed orally Given iv or sc Doesn’t cross BBB & Placental barrier Metabolized in liver by heparinase , metabolites excreted in urine During heparin therapy , the activated partial thromboplastin time ( aPTT ) monitoring is necessary Should be maintained at 1.5 – 2.5 times the control

11. Heparin – Adverse effects Bleeding Heparin induced thrombocytopenia Transient & reversible alopecia Osteoporosis Hypersensitivity reaction

12. Heparin - Contraindication Bleeding disorders Severe hypertension, abortion, piles, gi ulcers Ocular & neurosurgery Chronic alcoholics, cirrhosis, renal failure Aspirin & other antiplatelet drugs should be cautiously used

13. Low molecular weight heparins (LMWH) Mol.wt 3000 to 7000 Isolated from standard heparin by gel filtration chromatography Produce anticoagulant effect by antifactor Xa activity Given s.c

14. LMWH: Advantages over Heparin LMWH have smaller effect on aPTT Less interference with haemostasis Thrombocytopenia- less frequent Better s.c bioavailability Longer duration of action

15. LMWH- Indications Prophylaxis of deep vein thrombosis and pulmonary embolism Treatment of established deep vein thrombosis Unstable angina

16. Heparinoids Heparan sulfate Heparin like natural substance Less potent anticoagulant than heparin

17. Heparin antagonist- Protamine sulphate Strongly basic, low mol. wt protein obtained from sperm of Salmon fish 1mg of Protamine sulfate neutralises 100U of heparin Treatment of Heparin induced bleeding

18. Oral Anticoagulant: Warfarin They act directly by interfering with the synthesis of Vit K dependent clotting factors Competitive antagonist of Vit K Factor VII, IX, X (INACTIVE) Factor VII, IX, X (ACTIVE) Vit K (ACTIVE) Hydroquinone Vit K Epoxide NADH NAD Epoxide reductace WARFARIN

19. EPOXIDE REDUCTASE

20. Onset & duration depends on the half lives of clotting factors VII – 6 hr IX – 24 hr X - 40 hr II - 60 hr Pharmacokinetics : Completely absorbed Highly bound to plasma proteins Crosses placenta T1/2- 36-48 hrs Duration of action 3-6 days

21. Warfarin - adverse effects Bleeding Teratogenic effect Other adverse effects : alopecia, dermatitis, diarrhoea

22. Warfarin - drug interaction Enhance anticoagulant action Broad spectrum antibiotics Aspirin Phenytoin , Probenecid Chloramphenicol , Erythromycin Reduce anticoagulant action Barbiturates, Rifampicin Oral contraceptives

23. Therapeutic uses of anticoagulant Deep vein thrombosis & pulmonary embolism Myocardial infarction Unstable angina Vascular surgery, haemodialysis

24. thankyou