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Therapeutics Exam 2 > Anticoagulation > Flashcards

Anticoagulation Flashcards

0
Q

Intrinsic Pathway

A

Damage to blood vessel
Negatively charged surface
Factor 12…11…9…10(with 7a)…2(thrombin)…1(fibrin)

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1
Q

Extrinsic pathway

A

Damage to tissue outside the vessel
Trauma
Tissue Factor
Factor VIIa…X (with IX)

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2
Q

Hypercoaguable states

A 
FVL
Prothrombin (20210A) gene mutation
Antithrombin, Protein C and S Deficiency
Antiphospholipid antibodies (lupus)
HYPERhomocysteinemia
IBD
Nephrotic Syndrome
Pregnancy
Malignancy
Drug Induced
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3
Q

Ideal anticoagulant

A 
Oral
Daily dose
Rapid onset/offset
Predictable PK/PD
Few food/drug interactions
Fixed doses
Wide therapeutic window
Easily reversed
No monitoring
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4
Q

List Factor Xa Inhibitors

A

Fondaparinux
Rivaroxaban
Apixaban

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5
Q

List Direct Thrombin Inhibitors

A

Argatroban
Bivalrudin (Angiomax™)
Dabigatran (Pradaxa™)

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6
Q

List LMWH’s

A

Enoxaparin (Lovenox™)

Dalteparin (Fragmin™)

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7
Q

Heparin routes of admin

A

Parenterally (IV and SQ) rapid acting anticoagulant

Not IM - why?

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8
Q

Heparin MOA

A

Potentiates the action of antithrombin III
…thereby inactivating thrombin
…as well as activated coagulation factors 9, 10, 6 and 7, and plasmin
…prevents conversion of fibrinogen to fibrin

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9
Q

Heparin Labeled Indications

A

Px/Tx of thromboembolic disorders

Anticoagulant for extracorporeal and dialysis procedures

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10
Q

Heparin Unlabeled Indications

A

STEMI/NSTEMI
USA
During PCI (stent)

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11
Q

Heparin ADE’s

A 
Bleeding
Bruising at admin sites
HIT
Osteoporosis
HYPERkalemia
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12
Q

Increases risk of bleeding with heparin

A 
Surgery
Hemostatic defects
Heavy alcohol consumption 
Renal failure
Peptic ulcers
Cancer
Uncontrolled HT
History of hemorrhagic stroke
Recent GI bleeding
Thrombocytopenia 
Sever liver disease
Retinopathy
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13
Q

HIT

A

50% decrease in platelet count from pretreatment
Occurs 5-10 days after initiation of heparin or
Earlier with previous exposure (last 3-4 mo)
Diagnosed by assay for antibodies

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14
Q

Osteoporosis and heparin

A

Full therapeutic doses for extended (>6mo) period

Due to reduction in bone mineral density

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15
Q

HYPERkalemia and heparin

A

Heparin suppresses aldosterone production

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16
Q

Protamine sulfate

A 
Heparin reversal
Occurs within 5mins after IV admin
1mg neutralizes 100 units of heparin
Slow IV infusion
Max dose 50mg
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17
Q

Heparin Monitoring

A

aPTT/PTT (activated partial thromboplastin time)
CBC
Platelets

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18
Q

aPTT/PTT ranges

A

Institution specific
Correlates with plasma heparin conc 0.3-0.7 unit/
ml anti-Xa assay
Target aPTT range is 1.5-2.5 x control

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19
Q

LMWH MOA

A

Inactivate Factor Xa
Higher ratio of anti factor Xa to anti factor IIa
(thrombin) activity
More predictable PK, anticoagulant response
LMWH does not bind to heparin binding proteins
Peak 3-5 hrs
Half-life enox 4.5-7hr, dalteparin 2-5hr
Renal elimination

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20
Q

LMWH Labeled Indications

A

DVT Px in…
Hip or Knee replacement, or Abdominal surgery
Risk of thrombus complications in acute illness
Tx DVT/PE
USA
NSTEMI/STEMI

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21
Q

LMWH Unlabeled Indications

A 
Bridge therapy
DVT Px following mod-risk surgery
Anticoagulant in extracorporeal circuit in dialysis
ANTICOAGULANT OF CHOICE IN PREGNANCY
Anticoagulant for PCI
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22
Q

LMWH BBW

A

Risk for epidural and spinal hematomas resulting in permanent paralysis. Placement or removal of spinal catheter delayed for at least 12 hr after admin of Px dose and consider 24 hr after therapeutic dose. Post-procedural dose should be given no sooner than 4 hr after spinal catheter removal.

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23
Q

LMWH Admin

A

SQ in abdomen or outer thigh

IV in STEMI/PCI for enoxaparin

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24
Q

LMWH Dosing

A

Fixed or weight based every 12-24 hr according to product indication

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25
Q

LMWH Monitoring

A

Baseline CBC with platelet count and SrCr

Advantage over UFH- Does NOT require routine coagulation testing

Small effect on aPTT - NO need to monitor
Only in acute dosing in pregnancy or extreme obesity (>190 kg) or wt <50 kg

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26
Q

LMWH ADE’s

A 
Major bleeding
Easy bruising
Osteoporosis
HIT (less than UFH)
If pt has HIT history, do NOT use LMWH
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27
Q

Reversal for UFH

A 
Protamine sulfate
Reversal occurs w/in 5mins after IV admin
1mg neutralizes 100 units of heparin
Slow IV infusion
Dose NOT to exceed 50mg
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28
Q

Anticoagulant DOC in pregnancy

A

LMWH

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29
Q

LMWH elimination

A

Renally

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30
Q

Fondaparinux MOA

A

Indirect factor Xa inhibitor through interaction with antithrombin

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31
Q

Fondaparinux admin

A

Admin SQ DAILY into fatty tissue of abdominal wall

Do NOT expel air bubble from syringe before injecting

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32
Q

Fondiparinux elimination

A

Unchanged in urine

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33
Q

Fondaparinux peak and half-life

A

Peak conc in 2 hrs
Half life 17-24 hrs
Anticoagulant effect lasts 2-4 days after DC in normal renal fx

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34
Q

Fondaparinux contraindications

A

CrCl <30ml/min

Use caution in CrCl 30-50

35
Q

Fondaparinux Labeled Indications

A

DVT Px in…
hip or knee replacement
hip fractures
abdominal surgery

Tx of acute DVT/PE

36
Q

Fondaparinux Unlabeled Indications

A

NSTEMI/STEMI
USA
DVT Px in pts with Hx of HIT
Tx of acute thrombosis in pts with past Hx of HIT

37
Q

Fondaparinux monitoring

A

Baseline CBC/SrCr (DC if CrCl <30)

NO routine coagulation monitoring

38
Q

Fondaparinux ADE’s

A

Bleeding
major hemorrhage 1-3%
<6 hr post-op increases bleeding to 5%
Rare reports of HIT however, has been given to pts with current or Hx of HIT due to lack of an immune-mediated effect on plts

39
Q

Examples of biologic anticoagulant

A

UFH

LMWH

40
Q

Example of synthetic anticoagulant

A

Fondaparinux

41
Q

Anticoagulant with 100% Bioavailability

A

Fondaparinux

42
Q

Anticoagulant with only 30% Bioavailability

A

UFH

43
Q

Anticoagulant with half life of 17 hrs

A

Fondaparinux

44
Q

Anticoagulant with half life of 1.5 hrs

A

UFH

45
Q

Anticoagulant with half life of 4 hrs

A

LMWH

46
Q

Anticoagulant with renal excretion

A

LMWH

Fondaparinux

47
Q

Anticoagulant without renal excretion

A

UFH

48
Q

Anticoagulant with NO antidote

A

Fondaparinux

49
Q

Anticoagulant with partial antidote

A

LMWH

50
Q

Target for Fondaparinux

A

Xa

51
Q

Target for UFH and LMWH

A

Xa and IIa

52
Q

Pt with CrCl of 28 should be given anticoagulant of

A

Heparin because LMWH and Fondaparinux are eliminated renally

53
Q

List two Oral Factor Xa inhibitors

A

Rivaroxaban (Xarelto)

Apixaban (Eliquis)

54
Q

PC for rivaroxaban

A

15 and 20 mg MUST BE TAKEN WITH FOOD

55
Q

What is the safest new anticoagulant in renal patients?

A

Apixaban

56
Q

Rivaroxaban bioavailability

A 
10mg = 80-100%
15&20mg = ~66% MUST BE TAKEN WITH FOOD
57
Q

Rivaroxaban half life

A

5-9 hrs

11-13 hrs in elderly

58
Q

Rivaroxaban elimination

A

Primarily urine via active tubular secretion/feces

59
Q

Rivaroxaban substrates

A

CYP3A4/5
CYP2J2
PGP

60
Q

Apixaban bioavailability

A

50% May be taken with or without food

61
Q

Only anticoagulants indicated for stroke in nonvalvular afib

A

Rivaroxaban

Apixaban

62
Q

Only anticoagulant indicated for secondary Px against DVT/PE

A

Rivaroxaban

63
Q

Rivaroxaban labeled indications

A

DVT Px in hip/knee replacement
Stroke prevention in nonvalvular afib
Secondary Px against DVT/PE

64
Q

Apixaban labeled indications

A

DVT Px in hip/knee replacement

Stroke prevention in nonvalvular afib

65
Q

Apixaban substrates

A

CYP3A4/5 mainly

66
Q

Apixaban elimination

A

Feces / 25% Renal

Safest new anticoagulant in renal pts

67
Q

Apixaban half life

A

~12 hrs

68
Q

Monitoring for Oral Factor Xa Inhibitors

A

Bleeding
CBC with plts, SrCr, hepatic fx
Monitoring of coagulation tests not required

69
Q

Oral Xa Inhibitor Drug Interactions

A 
Avoid with STRONG CYP3A4...
inhibitors (clarithromycin, -azoles, -avirs, nefazodone) 
and inducers (rifampin, phenytoin, carbamazepine, St. John's wort)
70
Q

Oral Factor Xa Inhibitor Reversal

A

No specific antidote
Rivaroxaban NOT dialyzable
Therapy for severe hemorrhage: PCC or APCC or Recombinant Factor VIIa

71
Q

Dabigatran contraindications

A

Pts with mechanical heart valves

72
Q

DTI that does not require adjustment in renal dysfunction

A

Argatroban

73
Q

DTI that does not require adjustment in hepatic dysfunction

A

Bivalrudin

74
Q

DTI metabolized by CYP3A4

A

Argatroban

75
Q

Argatroban labeled indications

A

HIT-Monitor PTT

PCI-Monitor ACT

76
Q

Argatroban unlabeled indications

A

Extracorporeal circuit patency of CRRT

77
Q

Bivalrudin labeled indications

A

USA undergoing PTCA or PCI- monitor ACT

78
Q

Bivalrudin unlabeled indications

A

HIT- monitor PTT

STEMI undergoing PCI- monitor ACT

79
Q

DTI metabolized by blood proteases

A

Bivalrudin (B-Blood)

80
Q

Oral DTI bioavailability

A

3-7% for dabigatran (Pradaxa)

81
Q

Dabigatran metabolism

A

Metabolized to active form by plasma and hepatic esterases and hepatic glucuronidation

82
Q

Dabigatran substrate

A

P-glycoproteins

83
Q

Dabigatran elimination

A

Excreted in urine

84
Q

Dabigatran half life

A

12-17 hrs
Elderly 14-17 hrs
Mild-Mod renal 15-18 hrs (GFR 30-89)
Severe renal impairment 28 hrs (GFR <30)

85
Q

Dabigatran labeled indications

A

DVT/PE Tx and Px

Stroke Px in nonvalvular afib

86
Q

Dabigatran unlabeled indications

A

Postoperative thromboprophylaxis with total hip or knee replacement surgery

Therapeutics Exam 2 (15 decks)

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