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Killing biological cascades
 

Killing biological cascades

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    Killing biological cascades Killing biological cascades Presentation Transcript

    • Killing Biological Cascades:
      An Introduction to blood anticoagulants
    • Contents
      Biological Cascades
      Recap – Blood Clotting Mechanism
      Vitamin K – How it contributes
      Anticoagulants?
      Coumarins – Mechanism
      Heparin Derivatives – Mechanism
      So…are they different?
    • Cascades
      Consider the chemical reactions below
      A+ B  X
      A+ C  D
      D + E  F
      F + G  H
      B + H  X
    • -Why you don’t bleed to death-
      When wound occurs:
      Platelets adhere to collagen fibers and release clotting factors, starting the clotting mechanism.
    • 2-methyl-1,4-naphthoquinone (ZOMGWTFBBQUBER1337HAX?!)
      A.K.A Vitamin K.
      undergoes  reduction to a reduced form of vitamin K via enzyme EpoxideReductase. (VKOR)
      Reduced Vitamin K is then used to carboxylateGlu residues to Gla residues in various coagulation factors to activate them.
      Associated carboxylation enzyme turns Vitamin K to its oxidised state, which is then reduced by EpoxideReductase.
      Cycle continues.
    • Anticoagulants in a nutshell
      Substance that stops blood from clotting
      ( A.K.A it interferes with the clotting cascade somehow)
      Used primarily to prevent inappropriate blood clotting ( Eg: Pulmonary Embolism , Stroke, Myocardial Infarctions)
      We will be looking at 2 types of anticoagulants today, using the examples:
      Coumarins (Warfarin)
      Heparin & Derivatives ( Heparin)
    • Warfarin : How it works:
      Competitive Inhibitor of enzyme EpoxideReductase.
      Inhibits enzyme
      • Prevents Vitamin K from being reduced/recycled after caboxylation.
      • Prevents activation of coagulation factors via carboxylation
      • Coagulation factors cannot bind in a stable manner to wound
      • Cannot activate clotting to allow formation of a clot
      • Blood doesn’t clot.
      Because it is an competitive inhibitor, effects can be undone through providing high concentrations of Vitamin K.  Vitamin K is an antidote to Warfarin Poisoning.
    • Heparin : How it works
      Mucopolysaccharide in nature ( nitrogen groups on carbohydrates)
      Binds to thrombrin allowing thrombrin inhibition to take place
      Changes conformation of natural clotting inhibitor Antithrombin III (AT)
      • Strongly increases the efficency of AT
      • AT inactivates thrombin (electrostatic attraction) and factor Xa (changing active site conformation)
      • Coagulation pathway jeopardized.
    • C & C - two of the drugs with same effects? Why?
    • Conclusion Random Facts
      Due to the complimentary actions of both drugs, they are often taken together, with heparin stopped after a day or two.
      Fast action of heparin also means that it is used in various healthcare machines (Dialysis Machines, CPB pumps) to prevent clots forming in the tubes.
      choice of which anticoagulant to use will depend on the condition being treated as well as how the body reacts to the medication.
    • Questions?
    • No Moar Questions?
    • SO….
      Try Warfarin today! If it can kill rats, It definitely can kill you!
      This advertisement is of courtesy to our sponsor - Wilson Pharmaceuticals Pte Ltd
    • Thank You.
      -End the d**n thing lar. So boring can?-