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SUM '20 - Pharm II > Anticoagulants > Flashcards

Anticoagulants Flashcards

1
Q

Extracted from porcine (PIG) intestine (the majority) or bovine (COW) lungs where heparin is stored in

A

mast cells

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2
Q

**Anticoagulant effects are produced by binding to

A

anti-thrombin (AT)

[previously known as anti-thrombin III].

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3
Q

AT is a circulating

A

serine protease

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4
Q

**Heparin binds to AT enhancing the rate of thrombin-AT complex formation by

A

1,000 to 10,000 times

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5
Q

**Factors that are inhibited by AT:

A

Xa, IX, XI, XII

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6
Q

anticoagulation depends on the presence of adequate amounts of circulating

A

AT

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7
Q

Heparin potency is based on in vitro comparison with a

A

known standard

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8
Q

a unit of heparin is defined as the vol of heparin-containing solution that will prevent 1ml of….

A
  • 1ml of citrated sheeps blood
  • from clotting for 1 hour
  • after the addition of 0.2ml of 1:100 calcium chloride
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9
Q

Heaprin 1ml with 0.2ml caCl (1:100) will not clot in citrated sheep blood for:

A

1 hour

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10
Q

In the US, heparin must contain at least 120 (USP) units per milliliter. this equates to

A

120units/mL

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11
Q

**Precise pathway of heparin elimination is

A

uncertain

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12
Q

the influence of renal and hepatic dx on heparin is

A

less than other anticoagulants

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13
Q

Heparin is used for multiple purposes:

A
  • Prevention and tx of venous thrombosis
  • Prevention and tx of pulmonary embolism
  • Acute coronary syndromes
  • Perioperative anticoagulation for extracorporeal circulation and hemodialysis (bypass)
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14
Q

Onset of action for heparin is

A

immediate

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15
Q

Labs used to monitor heparin.

NORMAL ranges:
Established Therapeutic Levels:

A

WNL: aPTT: 30-35 seconds

Therapeutic: 45 - 87.5 seconds

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16
Q

aPTT is used to monitor heparin and maintain a ration of

A

1.5 to 2.5 times normal values for aPTT

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17
Q

Prolonged aPTT > 120 secs can be shortend by

A

omitting a dose.

-this is b/c heparin has a brief elim. half time

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18
Q

Generally low dose heparin may not require monitoring. This is because the doses and schedule are

A

well known

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19
Q

Some hospitals will monitor low dose heparin using an anti-Xa assay in place of aPTT because of the

A

potential variability of low dose and high dose regimens of heparin

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20
Q

ACT - Activated clotting time is used for higher heparin concentrations such as those used in

A

CABG

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21
Q

ACT is performed by mixing whole blood with an activating substance w/LARGE SURFACE such as (2)

“Activators”

A
  • Celite
  • Kaolin

activators

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22
Q

ACT acts on which pathway?

What Factor initiates activation of the clotting cascade?

A

activation through the classic INTRINSIC Pathway

Factor XII initiates activation of the clotting cascade

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23
Q

Activator (celite and kaolin) speeds up teh clotting time to normal values of aprox.

A

100-150 secs (1.5-2.5 mins)

depending on device used
*to measure the ACT and are based on detecting the onset of clot formation

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24
Q

ACT results between devices may be interchangeable? True/False

A

FALSE

results b/w devices may not be interchangeable

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25
Q

ACT is reliable for

A

high heparin concentrations >1.0 unit/ml

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26
Q

ACT May be influenced by: (4)

A
  1. Hypothermia
  2. Thrombocytopenia (low platelets increase clotting time)
  3. Presence of contact activation inhibitors (aprotinin)
  4. Preexisting coagulation deficiencies (fibrinogen, factor XII, factor VII)
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27
Q

In Aprotinin Therapy: it is recommended to use which activator-ACT? why?

A

kAolin-ACT rather than celite-ACT

as kaolin binds to aprotinin to minimize its effect.

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28
Q

• For cardiac surgery, a baseline ACT is determined:

A

 Before IV administration of heparin
 3- minutes after administration
 At 30 minutes intervals thereafter

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29
Q

**Target ACT in CABG surgeries is controversial but ranges between

A

350 – 400 seconds

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30
Q

ACT values may be misleading during CABG d/t heparin induced anticoagulation b/c of the effects of what two elements on the measurement system?

A

Hypothermia

Hemodilution

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31
Q

Allergic reaction to heparin are rare. If an IMMEDIATE reaction is noted….

A

HIT should be suspected

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32
Q

Reversal for HIT:

A

Protamine

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33
Q

Protamine is found in

A

salmon sperm

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34
Q
  • strong alkaline
  • polycationic (positive)
  • low molecular weight protein
  • found in salmon sperm

These are true of what medication:

A

Protamine

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35
Q

Protamine is positively charged alkaline that combines with the negatively charged acidic heparin to form a stable complex that is .

A

devoid of anticoagulant activity

*This complex is removed by the reticuloendothelial system within 20 minutes.

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36
Q

**Protamine Dose:

A

1mg for every 100 units of circulating heparin

*Example: 1000units of heparin given 1 hour ago. Currently 500 units circulating. Protamine dose (1mg x 5) = 5mg

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37
Q

Half life of Heparin

A

approx. 1 hour

* this is considered for protamine dosing

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38
Q

Two commonly administered LMWH

A
  1. enoxaparin

2. dalteparin

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39
Q
  • Heparin has an anti-Xa to an anti-IIa activity of 1:1
  • Enoxaparin has a corresponding ration varying between 4:1 and 2:1

-Pharmacokinetics of enoxaparin and dalteparin between patients are more consistent than heparin because they

A

bind less to proteins than does heparin.

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40
Q

VTE is thought to be better treated with LMWH than heparin in these patients:

A

-high risk medical and surgical patients

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41
Q

LMWH is greatly prolonged in

A

renal failure

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42
Q

with kidney failure, what should be used as an antigoagulant?

A

UFH

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43
Q

In pts with normal renal function, surgery should be delayed how long after the last dose of LMWH?

With renal dysfunction?

A

12 hours

renal = > 12 hours

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44
Q

Protamine neutralizes LMWH.

True or false?

A

False

Protamine does NOT neutralize LMWH

45
Q

Fondaparinux is also known as:

A

Arixtra

46
Q

Fondaparinux is a synthetic anticoagulant LMWH used for:

A

DVT
PE
Alt tx. for HIT (d/t long duration or use for concerns of sensitization)

47
Q

Unique feature of use for Fondaparinux :

A

Once a day administration

-15 hour half time

48
Q

Can Fondaparinux be used in pts with renal dysfunction?

A

it should not be

*renal elimination

49
Q

Danapariod (Orgaran) LMWH compound that attenuates ______ formation principally by _______.

A
  • Fibrin Formation

- by binding to AT (antithrombin)

50
Q

Danapariod (orgaran) is primarily eliminated by

A

the kidneys

51
Q

Surgery is associated with a 20-fold increase in

A

R/O VTE

52
Q

risk of VTE with surgery is associated with a

A

20-fold increase

53
Q

in general surgery patients, DVT incidence is

A

10-40%

54
Q

DVT is higher still (than general surgery) in what populations:

A
  • High Risk Surgery patients:
  • Orthopedic
  • Thoracic
  • Cardiac
  • Vascular
55
Q

Heparin and warfarin are the only drugs minimally affected in patients with

A

renal failure or dysfunction

56
Q

Risk of DVT is more protracted after hip surgery than after

A

general

-when it develops during the first few post op days

57
Q

due to the risk of VTE/DVT correlated to surgery, what is an intervention done on all patients while in the OR to prevent?

A

compression stockings/ SCDs

58
Q

• Surgical technique for hip surgery, which kinks the femoral vein, seems to stimulate proximal DVT in operated leg.

Therefore, what is most likely to develop?

A

Calf vein thrombosis is more likely to develop in either leg

59
Q

what is common and life threatening in major trauma

A

VTE

60
Q

with major trauma, a PE occurs in what % of pts

A

2-22%

61
Q

The 3rd most common cause of death in pts who survive the first 24hrs after a trauma is:

A

Fatal PE

62
Q

Bivalidrudin is a heparin replacement for what type of patients?

A

HIT+ patients

-for cardiac surgery on or off pump

63
Q

When do you stop Bivalirudin before surgery?

A

4-6hours before

64
Q

What patients need a dose adjustment for the use of Bivalirudin?

A

Renal impairment

-20% elminated by renal

65
Q

Argatroban is a synthetic direct thrombin inhibitor indicated for the use of

A

prophylaxis and tx of thrombosis

*In patients with or at risk of HIT undergoing PCI

66
Q

Does argatroban need to be adjusted in renal patients?

A

NO

-Hepatic elimination

67
Q

What DT inhibitors where first isolated from leeches?

A
  • Lepirudin
  • Desirudin

“L for L” Leeches and Lepirudin/Desirudin

68
Q

(“leechy”) Lepirudin was initially used in cardiac pts. Bleeding was a major problem due to its ability to

A

IRREVERSIBLY inhibit Thrombin

69
Q

Desirudin was first derived from?

A

leeches

70
Q

Desirudin is used to prevent

A

DVT after total hip or knee replacement

71
Q

Oral anticoagulants are derivatives of

A

4-hyroxycoumarin (coumarin)

72
Q

Most frequently used anticoagulant d/t predictable onset and duration is:

A

Warfarin

73
Q

Warfarin dose starts at:

A

5-10mg

74
Q

Average maintenance dose of Warfarin is:

A

5mg

75
Q

MOA for Warfarin

A

-Inhibits vitamin K epoxide reductase

that converts Vit K dependent coag proteins into active forms.

76
Q

Vitamin K dependent factors

A

“1972”

Factors II, VII, IX, and X

77
Q

anticoagulation effects of PO or IV Warfarin are

A

delayed 8-12 hours

78
Q

When should warfarin be stopped before surgery?

A

5 days

79
Q

peak concentration of warfarin occurs in

A

1 hour

80
Q

**warfarin % protein bound

what does this mean?

A

97%

-Long elimination half time of 24-36h

81
Q

this medication crosses the placenta and results in exaggerated effects on the fetus

A

warfarin

82
Q

can warfarin cross the placenta?

A

yes

exaggerated effects on fetus as well

83
Q

warfarin is metabolized into inactive metabolites that are gonjugated with glucronic acid and ultimately excreted in

A

bile and urine

84
Q

pts on VKA, perop check of what labs?

A

INR

85
Q

pts on oral anticoagulants can have minor surgery with them? true or false

A

true

Minor surgeries can be performed on pts taking oral anticoagulants

86
Q

**Major surgeries you want to stop oral agents how many days preop?

why?

A

1-3 days pre-op

to give PT time to return to w/in 20% of normal range

87
Q

when do you want to restart oral anticoagulants post op?

A

1-7 days

88
Q

• Newer oral anticoagulants have a rapid onset with therapeutic anticoagulation within hours of administration and do not

A

need routine monitoring

89
Q

Xarelto (Rivaroxaban)
Eliquis (Apixaban)

these are both what type of agent

A

Direct Factor Xa Inhibitor

Xa=Xa
Xa=Xarelto (rivaroXaban), apiXaban (eliquis)

90
Q

direct factor Xa inhibitors do not require

A

AT as a cofactor

91
Q

Direct factor Xa inhibitors have _______ greater selectivity for factor Xa than other serine proteases

A

> 10,000 fold

92
Q

**Epidural catheters should not be removed any earlier than hour many hours after the last dose of Xarelto?

A

18hrs

example was : 12p pt given xarelto, what’s the earliest catheter can be removed? A= 0600.

93
Q

after having an epidural catheter removed, when can the pt have their next dose of xarelto?

A

no earlier than 6 hours after removal of catheter

**6-8hrs

94
Q

Eliquis (apixaban) dosing and indications of use :

A
  • BID
  • Reduction of stroke and systemic embolism in a. fib.
  • DVT prophylaxis following hip/knee surgery
  • TX and reduction of DVT/PE
95
Q

Direct Thrombin inhibitors are:

A

Pradaxa / Dabigatran Etexilate

*ximelagatran (off market now but drug that provided proof of principle that oral agents that act via direct inhibition of thrombin were an effective mode of action)

96
Q

Pradaxa is approved for reduction of risk of stroke and systemic embolism in nonvalvular atrial fibrillation,

treatment of DVT and PE in pts who have been tx with a parenteral anticoagulant for 5-10 day and to reduce the risk of

A

recurrence of DVT and PE in pts who have been previously treated.

97
Q

Preferred measurement of effectiveness for pradaxa?

A

TT (or aPTT)

98
Q

after a catheter is removed, when can the next dose of pradaxa be given?

A

2 hours after removal

99
Q

ASA is considered an antiplatelet agent and is a mainstay tx for pts with:

A
  • Atherosclerotic vascular disearse
  • CAD

-therapy consistent w/the role of PLTs in atherosclerosis

100
Q

ASA prevents formation of thromboxane A2 by:

A

IRREVERSIBLY acetylates cyclooxygenase

101
Q

• Despite rapid clearance from body, effects of ASA on platelets are

A

irreversible and last for the life of the platelet (7-10 days)

  • Stop 7-10 days prior to surgery
  • Resume ASA ~ 24 hours post op after hemostasis
102
Q

What are two platelet inhibitors that are PRODRUGS?

A

Clopidogrel (Plavix)
Prasugrel (Effient)

Both are Thienopyridines

103
Q

plavix and effient irreversibly bind to P2Y12 receptors thereby blocking ADP binding.

when should these drugs be stopped prior to surgery?

regional?

A

• Stop 7 days before elective surgery and avoid regional until effects dissipated.

104
Q

appear more effective than Plavix in preventing thrombosis, although they increase the incidence of major bleeding, a problem with efficacy of all anticoagulants.

A

Prasugrel (Effient)

Ticagrelor (Brilinta)

105
Q

Platelet Glycoprotein IIB/IIIa Antagonists include:

A

Aggrastat (Tirofiban)
Integrelin (Eptifibatide)
ReoPro (abciximab)

106
Q

the antidote for GP IIb/IIIa antagonists drugs is:

A

dialysis

**Especially ReoPro - stop 72 hrs pre-op; 12-24hr 1/2 life

107
Q

the more potent produg is

A

Prasugrel (Effient)

108
Q

The prodrug with resistance occurring in 20-30% of patients is

A

Clopidogrel (Plavix)

*most widely used agent
flood pg. 657

109
Q

Protamine adverse reactions include:

A
  • anaphylaxis
  • acute pulmonary vasoconstriction
  • RV Failure
  • Hypotension

SUM '20 - Pharm II (30 decks)

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