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Pharmacology > Pharm 15- Procoagulants/Antifibrinolytics > Flashcards

Pharm 15- Procoagulants/Antifibrinolytics Flashcards

1
Q

Protamine

A

small protein that’s critical in maturation of sperm; stronly cationic protamine forms stable soluble salt w/ strongly anionic heparin

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2
Q

What ratio does protamine bind with heparin?

A

1:1; so for every 100 units of heparin 1 mg of protamine should effect heparin reversal

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3
Q

What happens to the coagulation pathway when Heparin: Protamine complex is formed?

A

Does not effectively interact with ATIII so the coagulation pathway continues unimpeded

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4
Q

What type of drug is protamine by itself? How does it work?

A

An anticoagulant; decreases thrombin generation by inhibiting Factor V activation

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5
Q

Why are dosing heparin/protamine protocols not 1:1 then?

A

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

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6
Q

How is protamine administered? How fast is onset of action?

A

Parenterally, rapid onset of action <5 minutes

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7
Q

What is the median half-life of protamine?

A

5 minutes

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8
Q

What is the median half-life of heparin?

A

1-2 hours

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9
Q

What is the metabolic fate of the protamine:heparin complex?

A

Has not been completely elucidated. One possibility is that some of the complex is degraded by fibrinolysin which would liberate free heparin

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10
Q

Heparin Rebound

A

Give your dose of protamine, ACTs normalize, over time it appears that increased bleeding happens often over hte course of minute to ~5 hours

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11
Q

What are some theories to explain heparin rebound?

A

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

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12
Q

What’s a more effective way of dosing protamine to prevent post-op bleeding?

A

Smaller initial doses of protamine with well-regulated, well-calculated post-bolus infusions are a more effective way to prevent post-op bleeding

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13
Q

Protamine is a component of what type of insulin?

A

Neutral Protamine Hagedorn

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14
Q

What are some other uses of protamine?

A

Only partially/unpredictably reverses LMWH (which sort of limits LMWH’s use)
No effect on fondaparinux

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15
Q

What are some precautions and problems of protamine?

A
  1. Protamine is an anticoagulant

2. Protamine rxns

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16
Q

What are some contributing factors to protamine reactions?

A

Rapid administration

Sensitization to protamine

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17
Q

What are some reasons a pt would have sensitization to protamine?

A 
Redo Surgeries
Fish allergies
Diabetics
Vasectomy
Excessive dosage
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18
Q

Protamine Reactions

A

Clinically manifest themselves as anaphylaxis and extreme hypotension, pulmonary hypotension, and CV collapse
Often necessitates crashing back on CPB

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19
Q

How are protamine reactions minimized?

A

Slow administration
Intra-aortic administration
Administration with steroids and antihistamines

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20
Q

Vitamin K

A

Fat soluble vitamin

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21
Q

Vitamin K is essential for the production of what factors?

A

Factors II, VII, IX, X

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22
Q

What are the two types of Vitamin K?

A
  1. K1: Phytonadione (Mephyton)

2. K2: Menaquinone

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23
Q

Where can you get K1: Phytonadione?

A

Green leafy vegetables

Supplemented

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24
Q

Where can you get K2: Menaquinone?

A

Meat, poultry, eggs, butter

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25
Q

How is Vitamin K related to VAD patients?

A

Destination vad and now theyre on warfarin; infections and bleeding problem kill cad patients (either too much or too little)

26
Q

What is the more clinically relevant form of vitamin K to perfusionists?

27
Q

How much vitamin K is given for warfarin overdosage?

A

1.0-2.0 mg of K1 is given by injection; this dose will lower the PT but not completely eliminate the desirable warfarin effects

28
Q

How must Vitamin K be given?

A

SLow IV (anaphylaxis is a common side effect); requires at least 6 hours to be effective

29
Q

What is the typical FFP dose for warfarin overactivity?

30
Q

What are two antifibrinolytics?

A 
Aminocaproic Acid (EACA, Amicar)
Tranexamic Acid (Cyklokapron, Lysteda)
31
Q

What are the two antifibrinolytics derivatives of? How do they work?

A

Synthetic derivatives of the amino acid lysine; both prevent plasminogen activation and directly inhibit plasmin which prevents fibrinolysis; both significantly reduce post bypass hemorrhage espeically in patinets who have received previous fibrinolytic therapy

32
Q

What is the difference between Aminocaproic Acid (Amicar) and Tranexamic Acid (Cyklokapron, Lysteda)

A

Tranexamic acid is 10x more potent than EACA

33
Q

How are both fibrinolytic durgs cleared?

34
Q

What percent are fibrinolytics used as part of the pump prime?

35
Q

How much Amicar is typically added to the pump?

A

5 or 10 grams

36
Q

What is an example of a serine protease inhibitor?

A

Aprotinin (Trasylol)

37
Q

How does Aprotinin (Trasylol) work?

A

Blocks plasmin and dose other ill-defined stuff to prevent post-op bleeding

38
Q

What are the benefits of using aprotinin (Trasylol)?

A

Dramatically reduces post-op blood loss

Particuarly in redos, jehovah’s witnesses, post fibrinolytic therapy

39
Q

What are the side effects of aprotinin (trasylol)?

A

Kidney failure
heart attacks
strokes

40
Q

When was aprotinin (trasylol) pulled from the market?

41
Q

What is aprotinin (trasylol) currently avaiable for?

A

Investigational use

compassionate use

42
Q

What is Desmopressin (DDAVP)

A

Synthetic form of ADH or vasopressin, a small protein

43
Q

How does Desmopressin (DDAVP) compare to vasopressin?

A

Desmopressin has much less pressor activity than vasopressin

44
Q

How does Desmopressin work?

A

Causes the release of vWF from vascular endothelium which increases Factor VIII and Factor XII activity; causes platelets adhesiveness to increase in patients with platelet dysfunction secondary to uremia or hepatic dysfunction

45
Q

What is Desmopressin useful for?

A

Mild Hemophilia A and vWF disease

46
Q

What forms is Desmopressin found in?

A

Many forms including nasal spray

47
Q

Describe the research and use of DDAVP

A

No research that indicates the use of DDAVP for bleeding post-bypass decreases the use of blood products; may be somewhat beneficial when administered in advance

48
Q

What are two blood products?

A

Fresh frozen plasma (FFP)

Cryprecipitate (Cryo)

49
Q

How is FFP formed?

A

Plasma is separated from whole blood and stored at <0 degrees F within 8 hrs of donation

50
Q

What is FFP often given for post bypass?

51
Q

FFP is preferably given with what?

A

ABO cross-matching

52
Q

What equipment may alter the use-habits of FFP in the future?

53
Q

FFP contains which factors?

A

I, II, V, VII, IX, X, Xi, XIII, At-iii and proteins C and S

54
Q

What is FFP used for?

A

Bleeding; immediate warfarin reversals
atiii deficinecy
large volumes of PRBC administration
colloidal volume replacement

55
Q

What dose of FFP will raise a pt’s atiii levels how much?

A

20ml/kg of FFP raises a patient’s ATIII by 20%

56
Q

Cryprecipitate is derived from what?

A

Precipitate that forms after FFP is thawed nad centrifuged

57
Q

How is cryo usually given?

A

as a pooled (4-6 units) product but abo cross-matching is considered desirable

58
Q

What is cryo used for?

A

Factor I, VIII , and vWF replacement; but levels of viii and vwf are iffy and cryo is not treated in any way to decrease the risk of viral exposure

59
Q

How much is 1 unit of cryo in mls?

60
Q

15 mls of cryo is how much fibrinogen

A

250-350 mg fibrinogen

Pharmacology (23 decks)

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