Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Anticoagulants naser


Published on

  • Be the first to comment

Anticoagulants naser

  1. 1. Anticoagulants Dr Naser
  2. 2. Case study• A 25-year-old woman presents to the emergency department complaining of acute onset of shortness of breath & pleuritic pain. she noted that her left leg was swollen and red 2 days prior . Her only medication was oral contraceptives. Family history was significant for a history of "blood clots" in multiple members of the maternal side of her family. The left lower extremity demonstrates erythema and edema and is tender to touch.
  3. 3. Common Thrombo Embolic Disorders For Drug Intervention• Post myocardial infarction• Prosthetic heart valves• Chronic atrial fibrillation• Acute deep vein thrombosis• Pulmonary embolism• Patients undergone orthopedic or gynecological surgery & in bed ridden patients
  4. 4. Hemostasis• Hemostasis: – Minimization or arrest of blood loss• Haemostatic mechanisms – Vasoconstriction – Platelet plug formation – Blood coagulation (Formation of clot)
  5. 5. Factors involved in coagulationFactor I: Fibrinogen Factor IX: Christmas factor / AntiFactor II : Prothrombin HB/ PTCFactor III:Tissue factor/ tissue Factor X: Stuart –Prower factor thromboplastin Factor XI: PTAFactor IV : calcium Factor XII: Hageman FactorFactor V: proaccelerin Factor XIII: Fibrin Stabilizing FactorFactor VII: stable factor/ proconvertinFactor VIII: antihaemophilic factor A
  6. 6. Extrinsic Pathway Intrinsic Pathway Tissue Trauma Damaged endothelial cells/ contact with glass VII TF XII XIIa XIa XI Activation of VIIa platelets VIIa Ca2+ Ca2+ IXa IX PL Ca2+ PL VIIIa VIII PL (Used in X Xa X cascade) Va Ca2+ PL XIII Prothrombinase Ca2+Prothrombin Thrombin XIIIa Stabilized Fibrin Fibrinogen fibrin threads insoluble
  7. 7. Fibrinolytic system • The process of dissolution of clot is called fibrinolysis Endothelial cells t-PAPlasminogen Plasmin Digests fibrin
  8. 8. Natural anticoagulant mechanisms• Prostacyclin (PGI2) – Inhibits action of TXA2• Antithrombin III: – blocks the action of factors II,IX,X,XI,XII• Protein C: – Blocks the action of factors V &VIII – ↑ t-PA action• Heparan sulphate : – Cofactor , enhances activity of antithrombin III
  9. 9. Classification of anticoagulants• Used in vivo – Parenteral • Heparin, Low molecular weight heparins, heparinoids – Oral • Coumarin derivatives • Indandione derivatives• Used in vitro – Heparin – Calcium complexing agents • Sodium citrate, sodium oxalate, sodium edetate
  10. 10. Classification of anticoagulants (used in Vivo)Parenteral : Oral anticoagulants:• Heparin • Coumarin derivatives• LMW heparins – Warfarin, dicumarol, – Enoxaparin, acenocoumarol, dalteparin, ardeparin, ethyl-biscoumacetate nadoparin, reviparin • Indandione derivates• Heparinoids – Phenindione – Heparan sulfate, danaparoid, lepirudin, ancrod
  11. 11. Heparin• Discovered by Mc Lean in 1916• Mixture of sulfated mucopolysaccharides 10,000 to 20000 MW• Strong electronegative compound• Strongest organic acid in body• Present in all tissues containing mast cells• Commercially prepared from beef lung and pig intestinal mucosa
  12. 12. Mechanism of action SlowlyAntithrombin III Inactive Coagulation factors
  13. 13. + AT-III Heparin Heparin AT- Fast III complex•Heparin providesscaffolding for Heparin acceleratesclotting factors & Antithrombin IIIAT-III activity by 1000 fold•Induces Especially against IIaconfirmational & Xachanges in AT-IIIto expose itsinteractive site
  14. 14. Other actions of heparin• Antiplatelet – High doses inhibits platelet aggregation and prolongs bleeding time• Lipaemia clearing – Clears turbid postprandial lipaemic plasma by releasing lipoprotein lipase from vessel wall & tissues
  15. 15. Pharmacokinetics• Orally not absorbed -Large molecules• Route – IV/SC• Does not cross BBB/ Placenta• Metabolised by Heparinase in Liver• Heparin sodium - 5ml vials 1000 & 5000 units/ml• t1/2 – 1 hr
  16. 16. Dosage• 5000-10000 units I.V , 4-6 hrly or• IV bolus 5000 units followed by continuous 750- 1000 units/IV/hr• Deep SC 10000-20000 units every 8-12hrly• Low dose SC regimen 5000 units every 8-12hrly to prevent post operative DVT• Dose controlled by APTT (1.5-2.5 times normal) Total Clotting time (2 times the normal)
  17. 17. HEPARIN – ADVERSE EFFECTS1. Bleeding due to overdose2. Osteoporosis3. Thrombocytopenia4. Hypersensitivity (Anaphylaxis)5. Transient alopecia• Antidote – Protamine sulphate 50 mg in 5ml for IV 1mg IV for 100 units heparin
  18. 18. Contraindications• Bleeding disorders• Heparin induced thrombocytopenia• Severe hypertension• Threatened abortion, piles• SABE• Occular , neurosurgery , lumbar puncture• Chronic alcoholics, cirrhosis• Aspirin other antiplatelet drugs use cautiously
  19. 19. Protamine sulfate• Strongly basic LMW protein• Obtained from sperm of certain fish• 1 mg IV neutralizes 100 U of heparin• Needed infrequently to antagonize heparin action rapidly• Can act as week anticoagulant in absence of heparin• Rapid IV injection causes flushing and breathing difficulty
  20. 20. Low Molecular Weight Heparins• M.Wt : 3000-7000• Selectively inhibit factor Xa ,No effect on IIa• Used for prophylaxis of Deep Vein Thrombosis Pulmonary Embolism, Unstable angina • ENOXAPARIN: 20-40 mg S.C , O.D • REVIPARIN:13.8mg(0.25ml) S.C/OD for 5-10 days • NADROPORIN :0.3ml(3075 units) • TINZAPARIN :3500 units S.C every 24hr)
  21. 21. LOW MOLECULAR WEIGHT HEPARINS• Higher S.C bioavailability• Longer duration of action• Do not routinely require aPTT monitoring• Lesser antiplatelet action• Less antigenic• Less hemorrhagic complications• Better patient compliance
  22. 22. HEPARINOIDS• Used In patients developing thrombocytopenia with Heparin1. HEPARAN SULPHATE : less potent, better profile.2. LEPIRUDIN : Recombinant preparation of Hirudin . Inhibits Thrombin directly, it is indicated in patients with heparin induced thrombocytopenia.3. ANCROD : enzyme from Malayan Pit Viper venom Fibrinogen Slow IV infusion 2units/kg over 6hrs for DVT Unstable fibrin (Taken up by RE cells)
  23. 23. Oral Anticoagulants1924 – Hemorrhagic disease in cattle due to feeding of spoiledsweet clover (contained bishydroxy coumarin)
  24. 24. Mechanism of action carboxylated Descarboxy factors II,VII,IX,X factors II,VII,IX,XVitamin K reduced form Vitamin K oxidized formHydroquinone KH Epoxide KO VitK reductase Warfarin NAD NADH
  25. 25. Pharmacokinetics & dosage of oral Anticoagulants :DRUG t½ (hr) DURATION OF DOSAGE DOSAGE ACTION LOADING MAINTENANC (days) (mg) E(mg)Bishydroxy 25-100 4-7 200 for 50-100coumarin 2 daysWarfarin 36-48 3-6 10-15 2-10sodiumEthylbiscoum 24 1-3 900 300-600acetateAceno 18-24 2-3 8-12 2-4coumarolPhenindione 5 1-3 200 50-100
  26. 26. Warfarin Sodium• Most popular oral anticoagulant• Racemate• Absorbed orally, crosses placenta• 99% pl.protein bound• Partially conjugated with glucuronic acid• Available as 1,2.5 mg tablet• Can be given parenterally as it is water soluble
  27. 27. • Dose Regulation Of Oral Anticoagulants : By Prothrombin time• INR
  28. 28. • ADVERSE EFFECTS :1. Bleeding- antidote: Vit.K2. Teratogenic3. Agranulocytosis4. nephropathy5. Hepatitis by phenindione6. orange urine
  29. 29. DRUG INTERACTIONS Oral anticoagulant effect ed by ed by• Broad spectrum antibiotics • Barbiturates• Phenylbutazone • Rifampin• Aspirin • Oral contraceptives• Sulfonamides• Phenytoin
  30. 30. Uses of anticoagulants• Deep Vein Thrombosis & Pulmonary Embolism in bed ridden , old , post operative, leg fracture pts• MI – for short period till pts become ambulatory• Unstable angina• Rheumatic Heart Disease , Atrial Fibrillation• CerebroVascular Diseases• Prosthetic heart valves• Hemodialysis• Disseminated Intravascular Coagulation
  31. 31. ComparisonHEPARIN WARFARIN• Mucopolysaccharide • Coumarin derivative• Parenteral • Oral• Immediate onset • Delayed onset of action• Duration of action 4-6 hrs • 3-6 days• Activity invitro & in vivo • Only invivo• Blocks action of factor X & II • X synthesis of clotting factors• Antagonist - protamine • Antagonist is Vit K• Monitor aPTT • Monitor PT/INR