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IMCP I > Exam 5 - Coagulation Cascade & Anti-Coagulants > Flashcards

Exam 5 - Coagulation Cascade & Anti-Coagulants Flashcards

1
Q

What is the function of vitamin K?

A

Vitamin K makes the serine protease enzymes II, VII, IX, and X biologically active. Each of these proteins have glutamic acid residues that are carboxylated by vitamin K to form gamma-carboxyglutamic acids in order to activate them.

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2
Q

What are the proteins and factors, and cofactors involved in the Intrinsic Pathway (understand steps)?

A

HMWK and Prekallikrein, Kinnogen/Kallikrein, XII, XI, IX, X, II

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3
Q

What are the factors involved in the Extrinsic Pathway (understand steps)?

A

TF, VII, TF-VIIa complex, X, II

*TF-VIIa complex also activates the Protein C Pathway

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4
Q

What is the purpose of the Protein C Pathway?

A

Attenuation of the clotting process

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5
Q

What is a key coactivator in coagulation?

A

Ca2+

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6
Q

What are the functions of Protein C & Protein S?

A

They are anticoagulant factors that inactivate factors Va and VIIIa

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7
Q

Warfarin (Coumadin®) MOA:

A 
Inhibits Vitamin K‐2,3‐
epoxide reductase (VKER) and therefore the synthesis of vitamin K-dependent clotting factors which include factors 2, 7, 9 and 10, and the anticoagulant proteins C and S
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8
Q

Warfarin (Coumadin®) t1/2, Vd, onset of action:

A

Long t1/2 of 36 hrs; small Vd, 8-12 hours

*S‐isomer is 4X more potent than R‐isomer

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9
Q

Warfarin (Coumadin®) metabolism:

A

CYP2C9, 3A4, 1A2, 2C19

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10
Q

Warfarin (Coumadin®) AE:

A

Excessive bleeding

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11
Q

Warfarin (Coumadin®) monitoring:

A

Prothrombin time (PT)

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12
Q

Thrombin Inhibiting Agents MOA:

A

Blocks activity of thrombin, a serine protease involved in activating clotting factors (Factors II and X, platelets)

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13
Q

Heparin MOA:

A

catalyzes inhibition of factor proteases by AT‐III (1000‐fold greater than AT‐III alone): thrombin (IIa), Factor Xa and IXa

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14
Q

Heparin monitoring:

A

Activated partial thromboplastin time (aPTT)

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15
Q

HMWH MOA:

A

High affinity for AT-III, especially IIa and Xa

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16
Q

LMWH MOA:

A

Mainly Xa

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17
Q

Heparin contraindications:

A

HIT, significant thrombocytopenia, advanced hepatic or renal function

18
Q

Fondaparinux MOA:

A

Mediates inhibition of Factor Xa by antithrombin

19
Q

Fondaparinux t1/2:

A

t1/2 = 17 hrs

20
Q

Idraparinux MOA:

A

Mediates inhibition of Factor Xa by antithrombin

21
Q

Idraparinux t1/2:

A

t1/2 = 80 hrs

22
Q

Direct Thrombin Inhibitors MOA:

A

Blocks activity of thrombin, a serine protease involved in activating several clotting factors (Factors II and X, platelets)

23
Q

Hirudin and Lepirudin MOA:

A

Specific irreversible thrombin inhibitor, binds and inactivates fibrin‐bound thrombin

24
Q

Desirudin (Iprivask®) MOA:

A

Irreversible inhibitor due to cleavage at proline residue

25
Q

Desirudin (Iprivask®) DOA, t1/2:

A

DOA ~ 8‐10 hrs; half‐life (t1/2) ~ 2‐3 hrs

26
Q

Desirudin (Iprivask®) DDIs:

A

NSAIDs, anticoagulants, anti platelet, and SSRIs

27
Q

Bivalirudin (Angiomax®) MOA:

A

Reversible inhibitor due to cleavage at proline residue

28
Q

Bivalirudin (Angiomax®) DOA, t1/2:

A

short DOA ~ 1‐2 hrs; short t1/2

29
Q

Bivalirudin (Angiomax®) DDIs:

A

heparin, warfarin, and thrombolytics

***intended for use with ASA

30
Q

Argatroban MOA:

A

Univalent, direct, reversible inhibitor of thrombin

31
Q

Argatroban elimination, t1/2:

A

hepatic elimination, t1/2 = 1 hr

32
Q

Argatroban DDI:

A

none with CYP3A4

33
Q

Dabigatran etexilate (Pradaxa®) MOA:

A

Univalent direct reversible inhibitor of thrombin

34
Q

Dabigatran etexilate (Pradaxa®) t1/2, elimination:

A

t1/2 ~ 12‐17 hrs, renal

35
Q

Dabigatran etexilate (Pradaxa®) DDIs:

A

Pgp substrates / inhibitors; dronedarone; ketoconazole; verapamil

36
Q

Dabigatran etexilate (Pradaxa®) reversal:

A

Idarucizumab (Praxbind®)

37
Q

Rivaroxaban (XARELTO®) MOA:

A

selective, reversible, direct inhibitor of Factor Xa

38
Q

Rivaroxaban (XARELTO®) metabolism, elimination:

A

CYP3A4, 2J2
Substrate for Pgp and BCRP

hepatic and renal

39
Q

Rivaroxaban (XARELTO®) DDIs:

A

strong inhibitors / inducers of CYP 3A4 and Pgp  Ketoconazole, erythromycin, rifampin, phenytoin

40
Q

Apixaban (Eliquis®) MOA:

A

selective, reversible, direct inhibitor of Factor Xa

41
Q

Apixaban (Eliquis®) t1/2, metabolism:

A

CYP3A4, Pgp substrate and BCRP

42
Q

Apixaban (Eliquis®) DDIs:

A

CYP3A4 inhibitors: dose adjust

CYP3A4 inducers: avoid use

IMCP I (32 decks)

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