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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
Emergencies: use ____ or ____ (more common); warfarin is long term or prophylactic treatment.
heparin or LMWH
26
Safe INR range for most patients is _____. For patients with a prosthetic valve: _____.
2-3 | 2.5-3.5
27
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
Prothrombin Time (PT)
28
To evaluate intrinsic and common factors and investigate unexplained bleeding and monitor heparin therapy
Partial Thromboplastin Time (PTT)
29
When titrating to the appropriate INR, it is typical to start with ____mg/day warfarin.
2-10
30
Most patients start on ___ mg PO initially to carry minimal risk of bleeding and bring INR around 2 within 4-5 days.
5
31
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.
10
32
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).
2
33
Daily INR/PT in hospital until therapeutic x 2 days Once baseline is established: 2x week -> weekly -> every other week -> monthly
Plan for INR monitoring
34
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
10%
35
If you have to ____ a warfarin dose, recheck within 1 – 2 days If you ____ a warfarin dose, recheck within 1 – 2 weeks
hold, change
36
______ ______ of warfarin can be pharmacodynamic (physiological factors, clotting factors) and pharmacokinetic (CYP450, 2C9).
Drug interactions
37
Thyroid products, statins, azoles, azithromycin, cephalosporins, etc. all ___ INR.
increase
38
Estrogens, Vitamin K, Rifampin, Phenytoin...all _____ INR.
decrease
39
____ mg PO vitamin K will correct elevated INRs within 24-48 hrs.
25
40
____ mg IV vitamin K corrects elevated INR; good for anticoagulation prior to invasive procedures. ___ mg IV (high dose) will correct with 6-12 hrs.
0.5-1 | 10
41
_____ bleeding is the most common cause of fatal bleeding when taking warfarin.
intracranial
42
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?
cholesterol embolism
43
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
e. all of the above
44
Proteins C and S are dependent on _____ for synthesis.
Vitamin K
45
True/False: Heparin is NOT used to chronically interfere with the formation of thrombi.
True
46
LMWH is administered _____ when used for DVT prophylaxis.
SQ
47
How can heparin be administered?
IV, SQ
48
Which drug is the antidote for heparin?
Protamine
49
LMWHs include which of the following? a. enoxaparin b. warfarin c. coumadin d. heparin
a. enoxaparin
50
How much time is required for peak anticoagulant effect of Warfarin?
3 days
51
``` Which drugs act as synergists for Warfarin? A. Heparin B. Thyroid products C. Antibiotics D. all of the above ```
D. all of the above
52
``` Which of the following are Warfarin antagonists? A. Rifampin B. Vitamin K C. Estrogens D. all of the above ```
D. all of the above
53
``` 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. Prasugrel
54
``` Which of the following are IV platelet aggregation inhibitors? A. Abciximab B. Eptifibatide C. Tirofiban D. All of the above ```
d. all of the above
55
``` Which anticoagulant(s) acts as a platelet glycoprotein IIb/IIIa receptor antagonist? A. Heparin B. Warfarin C. Thrombolytic Agents D. Abciximab ```
D. Abciximab
56
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.
Cilostazol, dipyridamole
57
Huge difference between cilostazol and dipyridamole?
Dipyridamole (persantine) is inappropriate for use in the elderly
58
What disorder is cilostazol strongly contraindicated in?
CHF
59
What do LMWH, Eliquis, Xarelto, Savaysa all have in common?
They are all factor Xa inhibitors.

PHARM (5 decks)

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