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    Anticoagulant

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    Aslam Baltee
    1) Anticoagulants can be classified as indirect thrombin inhibitors like unfractionated heparin and low molecular weight heparins, direct thrombin inhibitors like argatroban, and vitamin K antagonists like warfarin. 2) Heparin is a heterogeneous group of polysaccharides that works primarily by activating antithrombin III to inhibit thrombin and other clotting factors. Its effects are immediate but short-acting whereas warfarin's effects are delayed but long-lasting as it inhibits vitamin K-dependent clotting factor synthesis in the liver. 3) The main uses of heparin are for preventing thrombosis in surgery, heart attacks, and dialysis while war

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    Anticoagulant

    Uploaded by

    Aslam Baltee
    153 views34 pages
    1) Anticoagulants can be classified as indirect thrombin inhibitors like unfractionated heparin and low molecular weight heparins, direct thrombin inhibitors like argatroban, and vitamin K antagonists like warfarin. 2) Heparin is a heterogeneous group of polysaccharides that works primarily by activating antithrombin III to inhibit thrombin and other clotting factors. Its effects are immediate but short-acting whereas warfarin's effects are delayed but long-lasting as it inhibits vitamin K-dependent clotting factor synthesis in the liver. 3) The main uses of heparin are for preventing thrombosis in surgery, heart attacks, and dialysis while war

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    16. Anticoagulant

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    1) Anticoagulants can be classified as indirect thrombin inhibitors like unfractionated heparin and low molecular weight heparins, direct thrombin inhibitors like argatroban, and vitamin K antagonists like warfarin. 2) Heparin is a heterogeneous group of polysaccharides that works primarily by activating antithrombin III to inhibit thrombin and other clotting factors. Its effects are immediate but short-acting whereas warfarin's effects are delayed but long-lasting as it inhibits vitamin K-dependent clotting factor synthesis in the liver. 3) The main uses of heparin are for preventing thrombosis in surgery, heart attacks, and dialysis while war

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    153 views34 pages

    Anticoagulant

    Uploaded by

    Aslam Baltee
    1) Anticoagulants can be classified as indirect thrombin inhibitors like unfractionated heparin and low molecular weight heparins, direct thrombin inhibitors like argatroban, and vitamin K antagonists like warfarin. 2) Heparin is a heterogeneous group of polysaccharides that works primarily by activating antithrombin III to inhibit thrombin and other clotting factors. Its effects are immediate but short-acting whereas warfarin's effects are delayed but long-lasting as it inhibits vitamin K-dependent clotting factor synthesis in the liver. 3) The main uses of heparin are for preventing thrombosis in surgery, heart attacks, and dialysis while war

    Copyright:

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    of 34

    ANTICOAGULANTS

    By Dr Ayesha Afzal

    CLASSIFICATION

    INDIRECT THROMBIN INHIBITORS Unfractionated Heparin Low molecular weight Heparins Enoxaparin Dalteparin Fondaparinux DIRECT THROMBIN INHIBITORS Hirudin Lepirudin Argatroban Dabigatran

    VITAMIN K ANTAGONISTS Coumarin Derivatives Warfarin , Dicoumarol Nicoumalone , Acenocumarol Indandione Derivatives Phenindione, Diphenindione, Anisindione. CALCIUM CHELATORS K- Oxalate K- Citrate Na Citrate EDTA (Etmylene Diamine Tetra Acetic Acid)

    HEPARIN - CHEMISTRY
    Heparin consists of Heterogenous group of straight chain anionic mucopolysaccharides of molecular weights that average 15000. Commercial heparin consists of polymers of two repeating sulphated disaccharide units. These are D-glucosamine-Liduronic acid and D-glucosamine-D-glucuronic acid.

    HISTORY SOURCE PHYSIOLOGICAL ACTIONS MOA


    Anticoagulant Effect Lipolytic Effect

    PHARMACOKINETICS

    Route of administration Distribution Metabolism

    Heparin Dose is prescribed in Units


    Unit of Heparin
    The USP unit of Heparin is defined as the quantity of Heparin that prevents 1.0 ml of citrated sheep plasma from clotting for 1 hour after the addition of 0.2 ml of 1% Calcium chloride (CaCl2) solution.

    Heparin
    Standard Heparin or Unfractioned Heparin (UFH) MW 5000-30000
    Low MW Forms of Heparin preparations (2000-6000 MW) Enoxaparin Tinzaparin Dalteparin Fondaparinux

    Control of Heparin Doses


    Whole blood Clotting time to be maintained at 2-3 times the control value. OR Activated Partial Thromboplastin Time (aPTT) maintaining 1.5 2.5 times control reading. (most commonly employed)

    Heparin Doses:Treatment of Coronary / Thrombosis/ Thromboembolism 5000 10,000 Units I/V bolus then 1000 U/hr 10,000 U bolus, then 5000-10,000 U 4 hrly Intermittently 1/V Major Surgery for prevention of Thromboembolism S/C dose 5000 units 2 hours before major operation followed by 5000 units 8 hrly for 7 14 days. Low dose (Minihep) 5000U S/C

    THERAPEUTIC USES
    1. To depress clotting during the first 36 - 48 hours of oral anticoagulant therapy for the treatment of venous thrombosis and pulmonary embolism or may be employed as the sole anticoagulant for a longer period in pts who experience recurrent thromboembolism despite adequate oral anticoagulant therapy e.g. Trousseaus syndrome. 2. To prevent clotting during open heart surgery (cardiopulmonary bypass) 3. To prevent clotting during Haemodialysis. 4. Acute myocardial infarction.

    5.

    6. 7.

    In combination with thrombolytics for revascularization and in combination with glycopotein IIb/IIIa inhibitors during angioplasty and placement of coronary stents Drug of choice in pregnancy when an anticoagulant must be used. Low- dosage Heparin used in preventing post operative DVT (Deep Venous Thrombosis) and Pulmonary Embolism.

    8.

    To Prevent Venous Thrombosis during pregnancy and puerperium for 5-6 weeks after delivery. 9. Used intraperitoneally during Peritoneal Dialysis. 10. To clear intravascular cannulae. 11. DIC 12. To preserve blood in vitro.

    ADVERSE EFFECTS
    Overdose may cause bleeding. A painful, blue-ting discoloration of the planter surfaces and sides of toes. Thrombocytopenia Transient Alopecia Diarrhoea Allergic Reactions: Urticaria, Asthma and Anaphylactic shock. Osteoporosis leading to spontaneous vertebral fractures.

    Thrombosis in very high doses due to depletion of antithrombin-III. Abnormalities in liver functions Skin lesions at the site of SC injections

    ANTIDOTE
    Protamine sulphate obtained from Salmon sperm Heparin

    1% solution given I / V.
    For each Heparin (100U) 1 mg of Protamine sulphate. LMWH

    CONTRAINDICATIONS
    1. 2. 3. 4. 5. 6. 7.
    Hypersensitivity to the drug Haemophilia Thrombocytopaenia Purpura Severe hypotension Intracranial Haemorrhage Infective endocarditis

    8. Active TB 9. Ulcerative lesions of GIT 10. Threatened Abortion 11. Visceral Carcinoma 12. Advance Hepatic & Renal disease 13. Recent operation on Eye, Brain & Spinal
    Cord 14. During Lumbar Puncture

    ORAL ANTICOAGULANTS
    WARFARIN Na PHENINDIONE
    CHEMISTRY

    WARFARIN
    PHARMACOKINETICS

    Dose: Initial dose: 5 10 mg Maintenance dose: 5 7 mg daily.

    MOA of Oral Anticoagulants

    THERAPEUTIC USES OF WARFARIN


    1. 2. 3. 4. 5. 6. Acute MI. DVT . Pulmonary Embolism. Cerebrovascular diseases. Atrial Fibrillation. Cardiac Surgery.

    Control
    I One stage Prothrombin Time
    Ratio of the Prothrombin Time of patients III plasma to the Prothrombin Time of control plasma being kept at 2.5 3.5

    II INR =

    PT pt
    PT ref

    ISI

    INR is International Normalized Ratio

    ISI is International Sensaty Index

    ADVERSE EFFECTS

    Bleeding Skin rashes Blood dyscrasias, Jaundice, Pyrexia, Nausea & Vomiting, Anorexia Pregnancy-produce Fetal and Neonatal bleeding Depression of Bone Formation Cutaneous necrosis due to decreased synthesis of Protein C Infarction of breast, Necrosis of fatty tissue, intestines and extremities Alopecia

    ANTIDOTE
    Phytonadione Dose : 10 25 mg slow I/V. Neonates 1mg slow I/V. Severe cases of bleeding:Phytonadione IV+ Fresh Frozen Plasma I/V. rVII

    INTERACTIONS
    Increased Sensitivity to Oral Anticoagulants 1. Displacement of anticoagulant from its binding
    to plasma protein.
    Phenylbutazone and numerous NSAIDs Sulphonamides, Co-trimoxazole Oral anti-diabetic agents Ethacrynic acid Mefenamic acid Nalidixic acid Aspirin and numerous non-steroidal antiinflammatory agents may also interfere with platelet function and prolong the bleeding time.

    2. Inhibition of microsomal enzymes or competition for


    them. Alcohol Disulfiram Chloramphenicol 3. Depression of the formation of factors II, VII, IX and X (i.e. vitamin K-dependent factors) in the liver. Quinine, Quinidine, Cincophen Thyroxine 4. Causation of Hepatic dysfunction Anabolic steroids 5. Reduction of Vitamin K production by intestinal bacteria. Tetracyclines

    6. Reduction of vitamin K absorption.


    Liquid paraffin 7. Uncertain Cimetidine causes increased sensitivity to warfarin Clofibrate probably causes reduced platelet function and a more rapid turnover of the vitamin-K-dependent clotting factors. 8. Renal damage. 9. Acute illness, weight loss or decreased intake of vitamin K.

    DIFFERENCES BETWEEN HEPARIN & WARFARIN


    HEPARIN Chemistry o Mucopolysaccharide Structure Large polymer, acidc WARFARIN

    o Coumarin Derivative
    o Small lipid soluble molecule o Semi-Synthetic

    Source o Bovine Lungs o Porcine int. Mucosa


    Site of action o Blood

    O Liver o Oral

    Route of Adm: o Parenteral (S/C, I/V)

    DIFFERENCES BETWEEN HEPARIN & WARFARIN


    HEPARIN WARFARIN
    o Slow (36 48 hrs)
    Limited by half lives of affected o Long (4-7 days) factors being

    Onset of action:
    o Quick (in seconds)

    Duration of Action
    o Short (10 15 min)

    Protein Binding
    o Nil heparin but not for LMM heparins o Extensive

    Monitoring aPPT for regular O PT

    Metabolites
    o Uroheparin Half Life 40-90 Min
    OS.Warfarim-7Hydroxy warfarin, o R.Warfarin- Warfarin alcohol

    15-70 hrs

    HEPARIN

    Pregnancy & Lactation o Safely given


    MOA

    WARFARIN o Contraindicated in Preg & lactation

    a. Acts by activating Antithrombin o Inhibits Vit K dependent III, forming a complex with synthesis of factor II, VII, IX Antithrombin III & activated and X in the liver by inhibiting factors IXa, XIa, Xa, XIIa, XIIIa , gamma-carboxylation of glutamate resides in the above mentioned accelerating the activity of factors, by inhibiting the enzyme vit Antithrombin III to inactivate the K Epoxide reductase. above factors & thrombin. b. Vasodilator c. Acts like Lipemic Plasma clearing factor o Nil o Nil

    HEPARIN

    WARFARIN O MI O D.V.T o Pulmonary Embolism o CVA o Atrial Fibrillation o Cardiac surgery with artificial valves implantation o Bleeding, Fetal bleeding o Fetal bone formation depressed o Protein C inhibition with issue necrosis o Interaction with enzyme inhibitors and inducers

    Therapeutics Uses
    o Open Heart surgery, o Perimtoneal dialysis, o Haemodialysis, D.V.T and Pulmonary Embolism o Acute M I o Pregnancy, Puerperium o DIC

    Adverse Effects
    o Bleeding o Allergic reactions o Diarrhea osteoporosis o Alopecia

    Antidote for over dosage


    (Protamine sulphate for regular heparin Vit K1 (phytonadione),

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