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Pharmacology > Anticoagulation Therapy > Flashcards

Anticoagulation Therapy Flashcards

1
Q

what is the first line of tx for sickle cell & what is the goal of therapy?

A

Hydroxyurea

  • reduce episodes of pain
  • reduce hospitalizations
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2
Q

what is the dosing frequency for Hydroxyurea and what is the time frame for clinical response??

A

QD PO - weight based

> slow therapeutic response ~ 3-6 months

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3
Q

what is the second line of tx for sickle cell and what are other treatments?

A

Second Line Tx: L-Glutamine (Endari): amino acid

  • monoclonal antibodies: Clavizunab
  • blood transfusions
  • stem cell transplant
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4
Q

what anticoag blocks vitamin K and requires PT/INR monitoring?

A

Warfarin (Coumadin)

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5
Q

what is a naturally occurring anticoagulant that inactivates thrombin and factor Xa?>

A

Heparin

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6
Q

what new anticoagulants are considered pure factor Xa inhibitors?

A

Rivarobaxan (Xarelto)

Apixaban (Eliquis)

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7
Q

what AC is a direct thrombin factor and what does it act on?

A

Dabigatran (Pradaxa) -> inhibits thrombin (factor IIa)

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8
Q

what are clinical indications for Warfarin?

A

Afib -> PT/INR monitoring monthly

prophylactic or treatment of DVT & PE

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9
Q

what are common side effects of Warfarin & which are the most worrisome?

A 
fever
rash
diarrhea
hepatitis
*** hematuria -> indication of internal bleed
*** hemorrhage
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10
Q

what is the dosing regimen for Warfarin and when must INR be monitored?

A
  1. Initiation: 2-5mg qd x2-4 days
  2. Check INR after 2nd or 3rd dose
  3. Adjust dose based on PT/INR
  4. After INR stabilizes, check INR BIW
  5. INR checked monthly once therapeutic
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11
Q

in what patients must you caution when they are prescribed warfarin?

A

elderly -> fall risk

patients w/ renal or hepatic failure -> more sensitive, watch CYP450

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12
Q

what is the goal INR for warfarin?

A

therapeutic range: 2-3

goal: 2.5

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13
Q

if a patient’s INR is > 3, what should be done?

A

hold Warfarin and recheck INR levels

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14
Q

how many days does it take for warfarin to stabilize?

A

5-6 days

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15
Q

what is the maintenance dose for warfarin?

A

2-10mg qd

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16
Q

what is a rare reaction to warfarin that is seen in patients with protein C or S deficiency?

A

“purple/blue toes syndrome”

|&raquo_space;> due to microembolization of cholesterol, which occurs after several weeks to months of therapy

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17
Q

aside from vitamin K, what is used for reversal of warfarin?

A

fresh frozen plasma

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18
Q

what are drug interactions for warfarin & why does this happen?

A

Amiodarone
Alcohol
Cimetidine (Tagamet)
Disulfiram
Abx: Macrolides, tetracyclines, quinolones
Phenylbutazone
»> all are metabolized by Cytochrome P-450 system

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19
Q

what drugs may increase INR levels in patients on warfarin?

A 
Cephalosporins
Tetracyclines- Doxycycline 
Fluoroquinolones
Macrolides 
Bactrim
Glucocorticoids 
Omeprazole
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20
Q

what drugs may decrease INR levels in patients on warfarin?

A 
PCNs
Vitamin K
Carbamazepine
Phenobarbital
Dilantin/Phenytoin
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21
Q

what are drug interactions for Heparin that may cause an additive AC effect?

A

PO anticoags
Salicylates & other antiplatelet drugs
> ASA
> NSAIDs: Ibuprofen, Naproxen

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22
Q

what drug-herb can increase the risk of bleeding for heparin?

A

horse chestnut

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23
Q

what are clinical indications for unfractionated Heparin and what is the major side effect?

A

DVT, PE, VTE prophylaxis

|&raquo_space;> Hemorrhage

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24
Q

what is the MOA for unfractionated Heparin?

A

binds to antithrombin III -> inactivating factors IIa, IXa, Xa, XIa, and XIIa = thrombin complex
» fibrinogen goes not convert to form fibrin

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25
Q

does the dose need to be adjusted for unfractionated Heparin in patients with renal insufficiency or
renal failure?

A

no (therapeutic doses)

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26
Q

what is the half life of unfractionated Heparin and why is this important?

A

1-2 hours -> dose-dependent and may be disproportionately prolonged at higher doses
*requires aPTT monitoring

27
Q

what are adverse reactions for unfractionated Heparin?

A 
#1: hemorrhage
thrombocytopenia (HIT) 
white clot syndrome
anaphylaxis
fever
28
Q

what is the tx of choice for VTE prophylaxis in patients with HIT?

A

Fondaparinux (Arixtra)

29
Q

what can happen to a patient with HIT if they are given unfractionated heparin?

A

antibodies to platelets -> triggers thrombin generation -> venous or arterial thrombosis

30
Q

what is the reversal used for unfractionated Heparin?

A

Protamine Sulfate

31
Q

what are contraindications for Protamine Sulfate?

A 
Hypersensitivity 
Any bleeding disorder       
Surgery of brain, eye, or spinal cord
Intracranial Hemorrhage
Infective Endocarditis
Hx of HIT
32
Q

what is the route of administration for unfractionated heparin and why is this important?

A

IV or SC -> hospital settings
> cheaper
> closer monitoring of aPTT

33
Q

what is the dose for prevention of PE for unfractionated heparin?

A

5,000 units SC q 8 to 12 hours

*weight based when starting

34
Q

what are the most common low molecular weight heparins (LMWH) and what is the freq of dosing?

A

Enoxaparin (Lovenox)

Dalteparin (Fragmin)

35
Q

what are the advantages for using LMWH?

A

increased bioavility d/t long half life
-decreased chance of induce thrombocytopenia
-more predictable -> lab monitoring is not required
*** outpatient therapy
> preloaded syringe

36
Q

what do LMWH primarily act on?

A

factor Xa - same as heparin but less binding

37
Q

when is Lovenox indicated?

A

prevention of DVT, PE

38
Q

why is Fondaparinux (Arixtra) used in patients with HIT (think of MOA)?

A

it is a synthetic selective factor Xa inhibitor with no antithrombin activity
» administered IV drip qd

39
Q

what must be considered when dosing Fondaparinux (Arixtra)?

A

renal dosing
»> CrCl 30-50 caution is advised
***** CrCl < 30 contraindicated

40
Q

why must a patient be started on Warfarin at least 5 days before discontinuing Heparin for outpatient treatment?

A

due to need for 5 day monitoring which allows warfarin to achieve full therapeutic effect

41
Q

how are the DOACs get metabolized and what is their mechanism of action?

A

DOACs: Apixaban & Rivaroxaban
Metabolized in liver
» directly inhibits factor Xa

42
Q

what is the reversal for Apixaban and Rivaroxaban?

A

Andexxa

disadvantage: only available in hospital and is very expensive

43
Q

what should you do if a pt on a direct oral anticoagulant starts to have bleeding and does not have access to Andexxa?

A

discontinue dose of DOAC

44
Q

what are the advantages of direct oral anticoagulants over UFH & LMWH (vitamin K anticoagulants)?

A

PO administration
onset: rapid
predictable therapeutic effect-> no routine PT/INR
*** short half-life

45
Q

how many days must a DOAC be held prior to surgery?

A

3 days

* as opposed to 5 in LMWH & UFH

46
Q

what are the disadvantages of new oral anticoagulants over VKAs?

A
  1. no routine coag monitoring -> no awareness if pt is noncompliant and cannot titrate dose
  2. short half-life -> less efficacy in non-compliant patients
  3. antidotes are very expensive
  4. may need dose adjustment for renal or hepatic dysfunction
47
Q

what is the maintenance dosing for Apixaban (Eliquis)?

A

5mg BID PO

48
Q

what is the VTE prophylaxis dose for Apixaban?

A

2.5mg BID

49
Q

what is the maintenance dose for Rivaroxaban (Xarelto)?

A

20mg QD

50
Q

What is the maintenance dose for Dabigatran (Pradaxa)?

A

150mg BID

51
Q

In all newer oral anticoagulants, what must be considered?

A

renal dosing -> must check CrCl

52
Q

if an 80 y/o M w/ afib weighs less than 60kg and has a Creatinine of 1.5, what should be done to their maintenance Eliquis dose?

A
  • reduce Eliquis to 2.5mg BID
    OR
  • switch to Xarelto
53
Q

what is considered in dosing Apixaban/Eliquis for afib patients?

A

age &raquo_space;»> 80
weight «&laquo_space;60 kg
Creatinine&raquo_space;»/= 1.5

*if pt has 2 out of 3 criteria -> must reduce dose to 2.5mg BID OR switch to Xarelto

54
Q

what are the interactions for Apixaban (Eliquis)?

A 
amiodarone
antiplatelet meds
carbamazepine
phenytoin
azole antifungals
diltiazem
rifampin
macrolides: clarithromycin, erythromycin
55
Q

in what situations would DVT prophylaxis be considered in starting temp anticoagulation therapy with Apixaban?

A

s/p TKR or total hip replacement

56
Q

What are other newer anticoagulants indicated for stroke prevention and embolus with non-valvular afib?

A

Edoxaban (Sayvasa)

Betrixaban (Bevyxxa)

57
Q

what is the maintenance dose for Dabigatran (Pradaxa) & what must be considered in patients?

A

150mg BID

-renal function

58
Q

what is the MOA for Dabigatran (Pradaxa) and major side effect?

A

inhibits factor IIa

-bleeding

59
Q

what is the reversal for Dabigatran (Pradaxa) & what is the benefit and disadvantage for it?

A

Praxbind/Idarucizumab

benefit: 100% immediate effect
con: very expensive

60
Q

when initiating therapy of Rivaroxaban (Xarelto) for patients, what must you counsel them on?

A

increased risk for bleeding

|&raquo_space; must take w/ food

61
Q

if switching a pt currently on Warfarin to Apixaban/Rivaroxaban, how should this be done?

A

discontinue warfarin and when INR is at 2, start Apixaban

*if INR < 2 -> can start right away

62
Q

if switching a pt currently on Apixaban or Rivaroxaban to Warfarin, how should this be done?

A

start warfarin w/ 2-3 day overlap

-when INR is therapeutic on Warfarin, OK to d/c Xa inhibitor

63
Q

when switching a pt currently on Heparin to direct oral ACs, is there overlap when starting?

A

no

Pharmacology (7 decks)

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