Pharm 15- Procoagulants/Antifibrinolytics Flashcards
Protamine
small protein that’s critical in maturation of sperm; stronly cationic protamine forms stable soluble salt w/ strongly anionic heparin
What ratio does protamine bind with heparin?
1:1; so for every 100 units of heparin 1 mg of protamine should effect heparin reversal
What happens to the coagulation pathway when Heparin: Protamine complex is formed?
Does not effectively interact with ATIII so the coagulation pathway continues unimpeded
What type of drug is protamine by itself? How does it work?
An anticoagulant; decreases thrombin generation by inhibiting Factor V activation
Why are dosing heparin/protamine protocols not 1:1 then?
Protamine is eliminated rapidly from the plasma (faster than heparin) so dosing protocols of 1.1:1.0 to 1.3:1.0 protamine: heparin have been developed
How is protamine administered? How fast is onset of action?
Parenterally, rapid onset of action <5 minutes
What is the median half-life of protamine?
5 minutes
What is the median half-life of heparin?
1-2 hours
What is the metabolic fate of the protamine:heparin complex?
Has not been completely elucidated. One possibility is that some of the complex is degraded by fibrinolysin which would liberate free heparin
Heparin Rebound
Give your dose of protamine, ACTs normalize, over time it appears that increased bleeding happens often over hte course of minute to ~5 hours
What are some theories to explain heparin rebound?
Free heparin released from the protamin:heparin complex; heparin’s variable half-life outlives protamine’s ~2 hour clinical effect; heparin from tissue stores, too much reversal protamine given; or it doesn’t exist and its a proline deficiency
What’s a more effective way of dosing protamine to prevent post-op bleeding?
Smaller initial doses of protamine with well-regulated, well-calculated post-bolus infusions are a more effective way to prevent post-op bleeding
Protamine is a component of what type of insulin?
Neutral Protamine Hagedorn
What are some other uses of protamine?
Only partially/unpredictably reverses LMWH (which sort of limits LMWH’s use)
No effect on fondaparinux
What are some precautions and problems of protamine?
- Protamine is an anticoagulant
2. Protamine rxns
What are some contributing factors to protamine reactions?
Rapid administration
Sensitization to protamine
What are some reasons a pt would have sensitization to protamine?
Redo Surgeries Fish allergies Diabetics Vasectomy Excessive dosage
Protamine Reactions
Clinically manifest themselves as anaphylaxis and extreme hypotension, pulmonary hypotension, and CV collapse
Often necessitates crashing back on CPB
How are protamine reactions minimized?
Slow administration
Intra-aortic administration
Administration with steroids and antihistamines
Vitamin K
Fat soluble vitamin
Vitamin K is essential for the production of what factors?
Factors II, VII, IX, X
What are the two types of Vitamin K?
- K1: Phytonadione (Mephyton)
2. K2: Menaquinone
Where can you get K1: Phytonadione?
Green leafy vegetables
Supplemented
Where can you get K2: Menaquinone?
Meat, poultry, eggs, butter
