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PHARM > Warfarin/Antithrombotics > Flashcards

Warfarin/Antithrombotics Flashcards

1
Q
  • Irreversibly inhibits COX-1,2
  • Dirt Cheap
  • OTC
  • In children can cause Reyes
A

Aspirin

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2
Q
  • Irreversibly inhibits binding of ADP to platelet receptors.
  • Inhibits the activation of GP receptors.
  • Hepatically metabolized (CYP450)
A

Clopidogrel and Prasugrel

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3
Q
  • Reversibly inhibits binding of ADP to platelet receptors.
  • Inhibits the activation of GP receptors.
  • Hepatically metabolized (CYP450)
A

Ticagrelor

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4
Q
  • Used with ASA in A-fib
  • Prodrug – therapeutic efficacy relies entirely on its active metabolite
  • Boxed warning for “poor metabolizers” – have shown to have higher rates of cardiovascular events as compared to normal metabolizers
  • Strong CYP2C19 inhibitors reduce antiplatelet effect (e.g., omeprazole)
  • Monitor signs of bleeding, Hgb, Hct periodically
  • Genotyping for CYP2C19
  • Cheap drug
  • Grapefruit is problematic, inhibits prodrug change to active drug
A

Clopidogrel (Plavix)

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5
Q

Poor metabolizers have higher rate of cardiovascular events; because they are holding onto the medication

Strong inhibitors: at risk for clots, very important drug interaction to note, monitor bleeding, hemoglobin, etc

A

Clopidogrel (Plavix)

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6
Q
  • ADP receptor antagonist approved to decrease thrombotic cardiovascular events in patients with acute coronary syndrome, unstable angina, MI.
  • Box warning: elderly (increased fatal intracranial bleeding. Lower weight pts (<60kg) increased bleeding risk, use lower dosing.
  • Contraindications: peptic ulcer, prior TIA/stroke.
  • CYP450 inhibitor, but efficacy not affected.
  • Keep in original container with desiccant, or in original blister packaging
A

Prasugrel (Effient)

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7
Q

-Reversible binding to P2Y12 ADP platelet receptor
-BID Dosing + 81 mg ASA
-Keep in original container
-ASA doses higher than 100 mg daily can reduce efficacy
-Adverse effects: bradycardia, dyspnea and gynecomastia in men
-Consider for patients who have had a cardiac event with clopidogrel and for reduced CYP2C19 activity due to genetic variations.
-Strong CYP3A4 interactions
Not studied with oral anticoagulants

A

Ticagrelor (Brilinta)

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8
Q

Abciximab, Eptifibatide, Tirofiban - Bind GP receptors, blocks the binding of fibrinogen and von Willebrand factor which impedes aggregation.

Administered with heparin and ASA.

A

Intravenous Platelet Aggregation Inhibitors

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9
Q
  • Antiplatelet and Coronary vasodilator
  • Increases intracellular cAMP which results in decreased synthesis of thromboxane A2
  • Usually given in combination with aspirin and used for stroke prevention or + warfarin after artificial heart valve replacement
  • Headache and orthostatic hypotension are common (inappropriate in the elderly)
  • Dosed QID - drawback; non-compliance
A

Dipyridamole (persantine)

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10
Q
  • Inhibits COX + persantine MOA properties (vasodilator activity - see above)
  • BID
  • Cannot substitute as 2 separate prescriptions
  • Protect from moisture
A

Dipyridamole ER (extended –release) 200mg/25mg aspirin (Aggrenox)

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11
Q
  • Oral antiplatelet agent with vasodilating activity.
  • Increases levels of cAMP in platelets and vascular smooth muscle preventing platelet aggregation.
  • Favorably alters lipid profile.
  • Good for claudication
  • S/E: HA, GI
  • C/I: CHF
  • Numerous drug interactions
  • Grapefruit is a no-no.
A

Cilostazol (Pletal)

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12
Q

Injectable Anticoagulants

A

Heparin (IV, SQ)

LMHW (SQ)

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13
Q

-Rapid acting
-Used acutely to interfere with the formation of thrombi
-Binds to antithrombin III and causes rapid inactivation of coagulation factors
-Administered intravenously or sub-cutaneously
-Monitor aPTT
-Effects occur in minutes (IV) or 1-2 hours (sub-q)
Half-life 1.5 hours
-Chief complication – bleeding
-Antidote – Protamine sulfate – antagonizes the anticoagulant effect of heparin (can also be an antidote for LMWH).
-Adverse effects – Dyspnea, flushing, bradycardia, hypotension with rapid infusion

A

Heparin

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14
Q
  • Treats and Prevents DVT and PE, Treats A-fib
  • No lab testing required
  • Few drug interactions
  • Activity independent of Vitamin K – no food drug interactions – MOA independent of the vitamin K coagulation factors.
  • More predictable dose effect
A

Newer oral agents, factor 10a inhibitors (Pradaxa, Eliquis, Xarelto, Savaysa, Bevyxxa).

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15
Q
  • Treats and Prevents DVT and PE, Treats A-fib
  • No lab testing required
  • Few drug interactions
  • Activity independent of Vitamin K – no food drug interactions – MOA independent of the vitamin K coagulation factors.
  • More predictable dose effect

More expensive than warfarin (and 2 have no antidote - Savaysa, Bevyxxa)

A

Newer oral agents, factor 10a inhibitors (Pradaxa, Eliquis, Xarelto, Savaysa, Bevyxxa).

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16
Q
  • BID for afib
  • decrease dose/renal impairment
  • C/I with mechanical heart valve.
  • Dyspepsia; Decreased efficacy with increased gastric pH
  • Caution in elderly due to renal fxn or underweight
  • Increased bleeding with ASA or Clopidogrel
  • Routine monitoring of coagulation tests NOT required.
  • Protocol for switching
A

Pradaxa

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17
Q
  • BID dosing
  • Not recommended in patients with prosthetic heart valves
  • Not recommended in severe liver impairment or CrCl < 15ml/min
  • Avoid strong CYP3A4 inducers like carbamazepine, phenytoin, phenobarbital, St. John’s wort, rifampin
  • Use caution with other antiplatelet agents and anticoagulants
  • Protocol for switching from Warfarin.
A

Eliquis (Apixaban)

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18
Q
  • A-fib – QD some data suggest once daily dosing insufficient, but BID dosing untested
  • Not recommended with prosthetic heart valves
  • Take with food
  • Check renal function periodically
  • Caution use in the elderly
  • Avoid use with other anticoagulants
  • Interacts with CYP3A4
  • Switch from warfarin – Stop warfarin then start rivaroxaban when INR < 3
  • Popular most prescribed in the class
A

Xarelto (rivaroxaban)

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19
Q
  • Factor Xa inhibitor
  • Once daily dosing
  • Avoid in patients with above normal renal function (CrCl >95ml/min)
  • Reduce dose with CrCl 15 – 50 ml/min
  • Switching from warfarin – Stop warfarin, initiate edoxaban as soon as INR falls <=2.5
  • No specific antidote
A

Savaysa

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20
Q
  • Factor Xa inhibitor
  • Approved 2018 (APEX Clinical Trial)
  • No data on switching to/from other agents
  • No specific antidote
A

Bevyxxa

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21
Q
  • Vitamin K antagonist
  • Employed for longterm prophylaxis of thrombosis in the prevention of venous thrombosis, PE, TIA, MI, thromboembolism with prosthetic heart valves, thrombosis with afib.
  • Treatment of Protein C and S deficiency.
  • Not used for emergencies
A

Warfarin

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22
Q

The factors _____ require vitamin K as a cofactor for their synthesis by the liver.

A

2, 7, 9, 10

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23
Q

Natural anticoagulation proteins ______ require vitamin K for their synthesis.

A

C and S

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24
Q

Protein C is depleted more rapidly, so when patients start taking Warfarin, you could cause a ______ state because you are depleting C and S. When you initiate a patient on warfarin, you also need to initiate a fast acting anticoagulant, such as heparin or LMWH as you are waiting for the warfarin to kick-in.

A

pro-coagulation

25
Q

Emergencies: use ____ or ____ (more common); warfarin is long term or prophylactic treatment.

A

heparin or LMWH

26
Q

Safe INR range for most patients is _____. For patients with a prosthetic valve: _____.

A

2-3

2.5-3.5

27
Q

To evaluate extrinsic and common factors; identify hemostasis and clot formation; good for monitoring naive patients at onset of warfarin therapy to avoid clot formation

A

Prothrombin Time (PT)

28
Q

To evaluate intrinsic and common factors and investigate unexplained bleeding and monitor heparin therapy

A

Partial Thromboplastin Time (PTT)

29
Q

When titrating to the appropriate INR, it is typical to start with ____mg/day warfarin.

A

2-10

30
Q

Most patients start on ___ mg PO initially to carry minimal risk of bleeding and bring INR around 2 within 4-5 days.

A

5

31
Q

Healthy outpatient dosing to achieve rapid INR can be ___ mg PO X 2 days. Large initial doses do not provide more rapid anticoagulation and are not recommended.

A

10

32
Q

Due to increased risk of bleeding in the elderly, malnourished, debilitated, in children, hepatic and/or heart failure…you should consider a ___ initial dose (2 mg).

A

2

33
Q

Daily INR/PT in hospital until therapeutic x 2 days

Once baseline is established: 2x week -> weekly -> every other week -> monthly

A

Plan for INR monitoring

34
Q

If the INR is not within the desired therapeutic range after excluding explanatory factors, a 5 to 20 percent ( ____ is good) increase or decrease in the total weekly dosage is required

A

10%

35
Q

If you have to ____ a warfarin dose, recheck within 1 – 2 days

If you ____ a warfarin dose, recheck within 1 – 2 weeks

A

hold, change

36
Q

______ ______ of warfarin can be pharmacodynamic (physiological factors, clotting factors) and pharmacokinetic (CYP450, 2C9).

A

Drug interactions

37
Q

Thyroid products, statins, azoles, azithromycin, cephalosporins, etc. all ___ INR.

A

increase

38
Q

Estrogens, Vitamin K, Rifampin, Phenytoin…all _____ INR.

A

decrease

39
Q

____ mg PO vitamin K will correct elevated INRs within 24-48 hrs.

A

25

40
Q

____ mg IV vitamin K corrects elevated INR; good for anticoagulation prior to invasive procedures. ___ mg IV (high dose) will correct with 6-12 hrs.

A

0.5-1

10

41
Q

_____ bleeding is the most common cause of fatal bleeding when taking warfarin.

A

intracranial

42
Q

A patient is 3-8 weeks on warfarin therapy and develops purple toe syndrome. What issue might have lead to this happening with the patient?

A

cholesterol embolism

43
Q

Which are causes of clot formation?

a. afib, CHF, MI, bed rest, paralysis
b. vascular injury, heart valve replacement, atherosclerosis
c. Protein C and S deficiency
d. estrogen therapy
e. all of the above

A

e. all of the above

44
Q

Proteins C and S are dependent on _____ for synthesis.

A

Vitamin K

45
Q

True/False: Heparin is NOT used to chronically interfere with the formation of thrombi.

A

True

46
Q

LMWH is administered _____ when used for DVT prophylaxis.

A

SQ

47
Q

How can heparin be administered?

A

IV, SQ

48
Q

Which drug is the antidote for heparin?

A

Protamine

49
Q

LMWHs include which of the following?

a. enoxaparin
b. warfarin
c. coumadin
d. heparin

A

a. enoxaparin

50
Q

How much time is required for peak anticoagulant effect of Warfarin?

A

3 days

51
Q 
Which drugs act as synergists for Warfarin?
A. Heparin
B. Thyroid products
C. Antibiotics
D. all of the above
A

D. all of the above

52
Q 
Which of the following are Warfarin antagonists?
A. Rifampin
B. Vitamin K
C. Estrogens
D. all of the above
A

D. all of the above

53
Q 
Which ADP receptor antagonist is similar to clopidogrel but has fewer thrombotic events and an increased risk of major bleeding?
A. Prasugrel
B. Eptifibatide
C. Clopidogrel
D. Ticlopidine
A

A. Prasugrel

54
Q 
Which of the following are IV platelet aggregation inhibitors?
A. Abciximab
B. Eptifibatide
C. Tirofiban
D. All of the above
A

d. all of the above

55
Q 
Which anticoagulant(s) acts as a platelet glycoprotein IIb/IIIa receptor antagonist?
A. Heparin
B. Warfarin
C. Thrombolytic Agents
D. Abciximab
A

D. Abciximab

56
Q

Which 2 drugs’ mechanism of action involve proposed interference with platelet function by increasing cAMP, by decreasing phosphodiesterase activity, or raising adenosine levels? These both also cause vasodilation.

A

Cilostazol, dipyridamole

57
Q

Huge difference between cilostazol and dipyridamole?

A

Dipyridamole (persantine) is inappropriate for use in the elderly

58
Q

What disorder is cilostazol strongly contraindicated in?

A

CHF

59
Q

What do LMWH, Eliquis, Xarelto, Savaysa all have in common?

A

They are all factor Xa inhibitors.

PHARM (5 decks)

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