Killing biological cascades
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- 1. Killing Biological Cascades:
An Introduction to blood anticoagulants
Recap Blood Clotting Mechanism
Vitamin K How it contributes
Heparin Derivatives Mechanism
Soare they different?
Consider the chemical reactions below
A+ B X
A+ C D
D + E F
F + G H
B + H X
4. -Why you dont bleed to death-
When wound occurs:
Platelets adhere to collagen fibers and release clotting factors, starting the clotting mechanism.
5. 6. 7. 2-methyl-1,4-naphthoquinone (ZOMGWTFBBQUBER1337HAX?!)
A.K.A Vitamin K.
undergoes reductionto 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.
Associatedcarboxylation enzyme turns Vitamin K to its oxidised state, which is then reduced by EpoxideReductase.
8. Anticoagulants in a nutshell
Substance that stops blood from clotting
( A.K.A it interferes with the clotting cascade somehow)
Used primarily toprevent inappropriate blood clotting ( Eg: Pulmonary Embolism , Stroke, Myocardial Infarctions)
We will be looking at 2 types of anticoagulants today, using the examples:
Heparin & Derivatives ( Heparin)
9. Warfarin : How it works:
Competitive Inhibitor of enzyme EpoxideReductase.
- Prevents Vitamin K from being reduced/recycled after caboxylation. 10. Prevents activation of coagulation factors via carboxylation 11. Coagulation factors cannot bind in a stable manner to wound 12. Cannot activate clotting to allow formation of a clot 13. Blood doesnt 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.
14. 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 ofAT 15. AT inactivatesthrombin (electrostatic attraction)and factor Xa (changing active site conformation) 16. Coagulation pathway jeopardized.
C & C - two of the drugs with same effects? Why?
17. ConclusionRandom 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.
19. No Moar Questions?
Try Warfarin today! If it can kill rats, It definitely can kill you!
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21. Thank You.
-End the d**n thing lar. So boring can?-