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PHRM 844: Therapeutics II > Anticoagulants Junk > Flashcards

Anticoagulants Junk Flashcards

1
Q

What clotting factors are found within the Extrinsic Pathway?

A

VII, TF, X

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2
Q

What clotting factors are found within the Intrinsic Pathway?

A

XI, IX, VIII, X

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3
Q

What clotting factors are found with in the Common Pathway?

A

V, X, Thrombin (II), Fibrin (I), XIII

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4
Q

What is the MOA for Warfarin?

A

To inhibit the Vitamin K Reductase
- Causing a DECREASE in clotting factors.

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5
Q

What is the CYP what activates Warfarin?

A

CYP2C9

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6
Q

How long does it take before you may start seeing the effects of Warfarin?

A

About 3-5 Days; because it takes time to deplete all of the clotting factors from Reduced Vit K
- II: 60-100 Hours; VII: 4-6 Hours; IX: 20-30 Hours; X: 24-40 Hours

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7
Q

What is the initial dose of Warfarin?

A

5mg once daily
- Should overlap with a UFH/LMWH/Xa for 5 day AND until INR is normal

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8
Q

How to reverse a Warfarin Overdose?

A

-Can give high amounts of Vit K, which will reverse the inhibition of Vit K Reductase. Allowing for the clotting factors to be made again
-PCC [contains II, VII, IX, X, Protein C & S]

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9
Q

How do the genetic difference affect CYP2C9?

A
  • 1*: normal wild type
  • 2*: decrease clearance by 40-70%
  • 3*: decrease clearance by 90%

-1/2: 20% dose reduction
-2/3 & 1/3: 35% dose reduction
-3/3: 80% dose reduction

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10
Q

How do the genetic difference affect VKORC1?

A
  • A: Lower Dose; Higher Sensitivity
  • G: High Dose; Lower Sensitivity
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11
Q

What is the cause of Warfarin Necrosis?

A

The initial dose of Warfarin will cause Protein C & S to become lower than the rest of the clotting factors [II, VII, IX, X] and also leaving factors V & VIII active as well = hypercoagulable
- can take with heparin to help with this

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12
Q

What is INR?

A

INR: the total time it take for the blood to clot

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13
Q

What drugs can increase INR?

A

Metronidazole, Amirodene, Cipro, Fluoxitine, Bactrim
- Will make it to where the blood clots slower

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14
Q

What drugs can decrease INR?

A

Rifampin
- Will make it to where the blood clots higher

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15
Q

What are the contraindications for Warfarin?

A
  • Pregnancy: has the ability to pass through the plaecenta.
  • Liver Disease: a lot of the clotting factors are made within the liver so if the liver is not making any of the clotting factors and warfarin decreases them even more = Warfarin will cause an INCREASED bleeding.
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16
Q

What is the MOA for heparin [UFH]?

A

It is going to bind to Anti-Thrombin, causing it to accelerate the action of it. This will cause inhibition of BOTH Thrombin and Xa; a long chain with a pentasaccharide binds to AT and wraps around and inhibits Thrombin or Xa.

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17
Q

What is the aPTT?

A

A test that determines how fast it takes for the blood to clot without TF

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18
Q

What are the adverse affects with UFH?

A

Iatrogenic Hemorrhage: hemorrhage at any site of injection
- >50 years old, HTN, Ulcers, Antiplatelet Drugs
HIT
Osteoporosis

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19
Q

What is HIT?

A

HIT - Thormbocytopenia: A decrease in the number of platelets

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20
Q

What is the mechanism of HIT?

A

Heparin will bind to the PF4 receptor on the platelet:
- Heparin + PF4 on the platelet will cause the antibody IgG to become activated. IgG will bind to Heparin + PF4 marking it for death. This is know as Type 2 [Immunogenic]; for first time users of Herparin, this may occur in 30 days while second time users may experience this within 1 day
-Heparin + PF4 on the platelet will cause the platelet to become activated, initiating the clotting cascade, causing an overall decrease in platelets

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21
Q

How to you reverse Heparin?

A

Protamine Sulfate: this will directly bind to the Heparin molecule causing inactivation.
- Doesn’t really affect the LMWH [Enoxiparin and Daltaparin]
- HAS NOT EFFECT AT ALL on fondaparinux

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22
Q

What is the MOA for Low Molecular Weight Heparins [LMWH]?

A

The MOA for the LMWH is pretty much the same as the MOA for UFH, but since this has a low molecular weight it the pentasaccharide chain is much shorter, ONLY inhibiting Xa.

23
Q

What is the dosing for LMWH?

A

Enoxiparin:
-Prevention: 30mg BID (surgery) & 40mg daily (medical?)
-Treatment: 1mg SQ BID or 1.5mg SQ Daily
-Renal dysfunction: 30mg BID (prevent) & 1mg SQ Daily (medical)

24
Q

Which ones work better within the Liver? UFH or LMWH?

A

UFH; LMWH do not!!

25
Q

Does LMWG cause HIT or Osteoporosis?

A

Can still cause it, but is very less likely to develop HIT

26
Q

What is the MOA for Fondaparinux?

A

It is the same MOA as UFN and LWMH, but this one is ONLY the pentasaccharides and will ONLY inihbit the Xa\

27
Q

What is the main preventions of Fondaparinux?

A

THA, TKA, Hip replacement, Abdominal surgery

28
Q

What are some of the dosing options of Fonadparinux?

A

Treatment: 2.5mg daily
Prevention: It is based on the patients weight;
- <50kg: 5mg
- 7.5-10kg: 50 - 100mg
- 10kg: 10mg

29
Q

What is the MOA for the Direct Factor Xa Inhibitiors?

A

They directly bind to factor Xa; stoping the activity of the common pathway.
- will affect multiple thrombin and fibrin

30
Q

What is the reversal medication for Direct Factor Xa Inhibitors?

A

Andexant Alfa: it will bind directly to the Direct Factor Xa Inhibitor - inhibiting them

31
Q

What are Direct Factor Xa Inhibitors used for?

A

Postoperative Prevention, DVT/PE Treatment, Secondary Prevention, Non-AFIB, VTE Prevention

32
Q

Postoperative Prevention dosing for Xa?

A

Rivaroxaban: 10mg DAILY for 12 days (hip) and 35 days (knee) [avoid: CrCl < 30]
Apixaban: 2.5mg BID for 12 days (hip) and 35 days (knee)

33
Q

Non-AFIB dosing for Xa?

A

Rivaroxaban: 20mg DAILY [15-50 CrCl = 15mg]
Apixaban: 5mg BID
-CONSIDERATION: >80 years old, <60kg, Scr >1.5 = 2.5mg
Edoxaban: 60mg DAILY [15-50 CrCl = 30mg]

34
Q

DVT/PE Treatment dosing for Xa?

A

Rivaroxaban: 15mg BID for 3 weeks, then 20mg DAILY
Apixaban: 10mg BID for 7 days, followed by 5mg BID
Edoxaban: 60mg DAILY
-CONSIDERATIONS: <60kg = 30mg DAILY & 5-10 parental anticoag [UFH or LMWH]

35
Q

Secondary Prevention dosing for Xa?

A

Rivaroxaban: 20mg PO DAILY
Apixaban: 2.5mg PO BID
-CONSIDERATION: after 6 months of initial therapy.

36
Q

VTE Treatment dosing for Xa?

A

Rivaroxaban: 10mg PO DAILY [avoid: CrCl < 30]
Betrixaban: 160mg PO (1DAY) then 80mg PO DAILY [ONLY INDICATION]

37
Q

What is the mechanism for Direct Thrombin Inhibitors?

A

Directly binds to Thrombin; inhibiting the formation of Fibrin = not making the crosslinked fibrin mesh.

38
Q

Are Direct Factor Xa Inhibitors used in patients that have a prosthetic heart valve?

A

No, its contraindicated

39
Q

What type of thrombin does Heparin affect? Direct Thrombin Inhibitors?

A

-Heparin ONLY affects soluble thrombin
-DTIs can affect BOTH soluble and fibrin-bound thrombin

40
Q

What are the DTI?

A

Argatroban (IV), Dabigitran (IV), Bivalirudin (PO)

41
Q

Which one of the DTIs are approved for treatment and/or prevention of HIT?

A

Argatroban
-Dabiiatran & BIvalirudin can also be used too?

42
Q

What medication can reverse the action of the DTIs?

A

Idariczumab: Monoclonal Antibody that bind directly to Dabigitran
-DOES NOT BIND TO THE OTHER DTIs

43
Q

What medication can be used in Valvular AFIB?

A

ONLY Warfarin: because of the slow onset

44
Q

What does Bivalirudin?

A

IV form of DTI
-0.7mg/kg then 1.75mg/kg/h
-Can be used in HIT & UFH alternative during PCI

45
Q

What does Argatroban?

A

IV form of DTI
-2mcg/kg/min
-Can be used in HIT & overlap with Warfarin until INR is >4?

46
Q

Postoperative Prevention dosing for Thrombin Inhibitors?

A

Dabigitran: Day of surgery use 110mg DAILY; NOT the day of surgery use 220mg DAILY; maintenance use 220mg DAILY
ONLY FOR HIP REPLACEMENT

47
Q

Non-Valvular AFIB dosing for Thrombin Inhibitors?

A

Dabigitran: 150mg BID [CrCl 15-50: 75mg BID]

48
Q

DVT/PE Treatment dosing for Thrombin Inhibitors?

A

Dabigitran: 150mg BID
-needs a 5-10 parental anticoag [UFH or LMWH]

49
Q

What is VIRCHOW’s Triad?

A

Its what can cause a thrombosis
-Hypercoag, statsis, endothelial damage
-give warfarin?

50
Q

What are the five D’s associated with warfarin?

A

Drugs, Drinking, Diseases, Diet, Doses
-Bleeding and Bruises

51
Q

What causes the increase in HDL within Niacin?

A

Apo-A

52
Q

What is CHA2DS2-VASc Score?

A

C-CHF (1)
H-HTN (1)
A-Age > 75 (2)
D- DM (1)
S- Stroke (2)
V- Vascular Disease (1)
A - Age 65-74 (1)
C- Famale (1)

53
Q

What is HAS-BLED score?

A

H- HTN (1)
A- Liver and renal function (1-2)
S- Stroke (1)
B- Bleeding (1)
L- INR (1)
E- Age >65 (1)
D- Drugs (1-2)

PHRM 844: Therapeutics II (11 decks)

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