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Anesthesia Pharm > Anticoagulants > Flashcards

Anticoagulants Flashcards

1
Q

Primary hemostasis

Describes the formation of platelet plugs

A
  • Adherence
  • Activation
  • Aggregation
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2
Q

What is the MOA of UF Heparin

A

UF Heparin

It inhibits and binds to antithrombin III –> it inhibits functions of factors Xa, IIa (thrombin), IXa, XIa, XIIa

more specific : IIa

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3
Q

type of heparin that is more specific for inhibition of Xa (anti- IIa activity lower)

A

Low Molecular Weight Heparin

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4
Q

are heparins dialyzable?

A

NO

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5
Q

How is UFH eliminated?

A

UFH = Endothelial metabolism

enoxaprain and dalteparin = renal excretion

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6
Q

Advantages and disadvantages of UFH

A

* oftentimes UFH tends to have a lot of variances

UFH infusion: if you need to do an emergent procedure it takes 3 hours ideally 4 hours to come out of the system entirely.

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7
Q

Advantages and disadvantages of LMWH

A

big down side: RENAL ELIMINATION

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8
Q

BIG ADVERSE EVENTS OF HEPARINS

what is the treatment?

A

HEPARIN INDUCED THROMBOCYTOPENIA

o Development of antibodies against heparin and platelet factor 4 complex that leads to progressive thrombocytopenia and arterial and venous thrombi

o Evaluate risk with 4T score before testing for heparin antibodies and serotonin release assay

o Treatment: direct thrombin inhibitors [exam]

BLEEDING

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9
Q

How does aPTT react to LMWH

A

In general, aPTT should not change wtih LMWH

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10
Q

How do you monitor LMWH?

A

Anti factor Xa [heparin assay]

o May be used in situations where aPTT may not be reliable for UFH (e.g., lupus anticoagulant)

o Assessment of LMWH activity
• Useful if renal failure, obesity, pregnancy, or concern for

decreased bioavailability
o Assessment in cases of heparin resistance

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11
Q

The result of aPTT in patients with Lupus anticoagulant

A

aPTTs are not going to be reliable

if you use Heparin

Anti Xa should be mentioned

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12
Q

will FFP reverse heparin?

A

no.

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13
Q

what is an antidote for heparin?

A

Protamine

Mechanism of action

  • Protein derived from fish sperm [anaphylaxis for pts with fish allergy]
  • Binds to UFH or LMWH to form complex that is broken down by reticuloendothelial system

Adverse effects (generally dose and infusion rate dependent)

  • Bleeding
  • Anaphylaxis
  • Patients on maintenance NPH insulin, men with vasectomy, known fish sensitivity
  • Acute pulmonary vasoconstriction [rate dependent]
  • Hypotension
  • Bradycardia

Administration

  • Max infusion rate: 20 mg/min [exam]
  • Slow infusion rate to decrease adverse effects
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14
Q

How much does 1 mg of protamine reverse?

A

1 mg of protamine reverses 80 -120 units UFH IV

Only UFH over the past 2-3 hours should be counted

  • Protamine half-life: 7 min; heparin half-life: 60-90 min

Administration

  • No more than 50 mg in 10 min period
  • Repeat doses may be needed to fully reverse UFH
    • 0.5 mg per 100 units UFH
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15
Q

Role of Protamine and LMWH

A

LMWH –> NO reversal agent

Protamine partially effective

o Can successfully neutralize anti-IIa activity, but partially effective at reversing anti-Xa activity

  • *Dose:**
  • *Enoxaparin**
  • 1 mg per 1 mg of enoxaparin given within previous 8 hours, max dose 50 mg; may repeat with 0.5 mg for every 1 mg enoxaparin if bleeding continues
  • May repeat with 0.5 mg per 1 mg enoxaparin if >8h has elapsed since enoxaparin dose

Dalteparin

  • 1 mg per every 100 anti-Xa units given over past 3-5 half-lives,
  • max dose 50 mg
  • May repeat with 0.5 mg for every 100 anti-Xa units
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16
Q

If someone is bleeding and they have HIT what is the last factor product that you would want to give them for a reversal?

A

4F - PCC

(Kcentra)

it has heparin in it

it is contraindicated in HIT

tx: you should give 3F - PCC

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17
Q

What is the MOA of Warfarin?

What clotting factors does it inhibit?

Why do people bridge when they start warfarin?

A

Mechanism of action: WARFARIN

  • Inhibits activation of vitamin K dependent clotting factors
    • Factors II, VII, IX, X + anticoagulants protein C and protein S
  • Inhibition of anticoagulant_s increases risk for hypercoagulability at initiation of VKA without bridging_
  • Full anticoagulant affect not usually achieved until at least 4 days when factor II levels are significantly decreased
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18
Q

What is the half-life of Warfarin?

A

really long: 20- 60 hours

metabolized by CYP2C9 and affected by drugs that inhibit the metabolism of it (ccb)

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19
Q

does warfarin have renal clearance?

what are the advantages and disadvatages?

A
  • none.
  • it has tons of hepatic clearance
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20
Q

Common drug interactions with Warfarin

A
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21
Q

Drugs that potentiate warfarin effects

A
  • Amiodarane
  • Diltiazem
  • Phenytoin [can also inhibit]
  • Fluconazole
  • Voriconazole
  • argatroban [direct thrombin inhibitor] –> WILL INCREASE INR [false elevation]
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22
Q

Inhibition of warfarin effects

A
  • Seizure meds
  • phenytoin
  • phenobarb
  • rifampin [will increase the metabolism of warfarin by inducing CYP450]
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23
Q

Reversal of Warfarin

What do you do with a supratherapeutic INR without bleeding?

A
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24
Q

What do you always have to give with 4 factor PCC?

why?

A

IV vitamin K

because 4 factor PCC half-life is shorter than Warfarin

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25
Q

How do you reverse Warfarin with minor bleeding?

A

IV Vitamin K (1-3 mg + may repeat)

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26
Q

How do you reverse Warfarin with Major bleeding?

A

4 factor PCC + IV Vit K ( 5-10 mg + may repeat)

FFP if PCC not available (remember that this is also volume)

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27
Q

How do you reverse Warfarin in elective/nonurgent surgery

How about urgent surgery?

A
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28
Q

MOA of Direct Thrombin Inhibitors

A
  • Binds to free thrombin and clot-bound thrombin
    • decreases conversion of fibrinogen to fibrin, thrombin generation, platelet activation
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29
Q

Drug of choice for the management of HIT

A

Direct Thrombin Inhibitors

30
Q

What are samples of Direct Thrombin Inhibitors

A

Bivalirudin

Argatroban

Desirudin

Dabigatran

31
Q

DTIs that are given IV

A

Bivalirudin

Argatroban

32
Q

Route of Elimination of

DTI

A

Bival –> kidneys

Argatroban –> liver

33
Q

Which drug should you give to a patient that has HIT that has shock liver?

A

Bivalurudin

34
Q

DIT that is oral, and longer acting (12-17 hours), very much dialyzable

A

Dabigatran

dialyze like crazy if you want it off

35
Q

If someone came to you at the later end of their therapy 3-5 half-lives after cessation of therapy what should you do?

A

No need to do anything

No role for reversal of presentation

36
Q

A patient presented with an overdose of Dabigatran (early within 2 hours ) what should you do?

A
  • Activated charcoal if administered within 2 H
  • Idarucizumab for reversal
    • ​Monoclonal antibody that binds specifically to dabigatran and acylglucuronide metabolites at ~350 times greater than that of thrombin –> neutralizes effects within minutes
    • 5 g (given as 2 separate 2.5 g doses within 15 min) IV x1
    • May repeat if elevated coagulation parameters and clinically relevant bleeding present or if second urgent surgery/procedure required
    • Dabigatran may be started 24 h after idarcizumab, if needed
37
Q

Why is supportive care in Bival, Argatroban, and Desirudin enough rather than reversing it?

A

due to short half-lfe

* if you have to absolutely [DOC] reverse activated factor 4 PCC can be used

NO ROLE FOR PLASMA

38
Q

What are samples of Direct Xa Inhibitors

A
39
Q

MOA of Directo Xa Inhibitors

A

Mechanism of action

  • Bind to free factor Xa and factor Xa bound to prothrombin complex
    • interrupts intrinsic and extrinsic coagulation cascade
    • prevents ultimate formation of thrombin
40
Q
A
41
Q

Are Direct factor Xa inhibitors dialyzable?

A

NO.

42
Q

is the monitoring of NOACs required?

A
43
Q

What is the reversal agent for Factor Xa Inhibitors rivaroxaban and apixaban?

A

Andexxa (first line for rivaroxaban, apixaban)

  • bolus then infusion
44
Q

What is the second line reversal for Factor Xa inhibitors?

A

Second line

o 4-factor prothrombin complex (4F-PCC) 25 units/kg for life- threatening bleeding [fair enough next choice from andexxa]

o 3F-PCC 25 units/kg or FEIBA 25 units/kg in patients with history of heparin induced thrombocytopenia

Plasma NOT routinely recommended

o Amount of plasma needed to overcome action of NOAC would likely cause fluid overload and adverse effects

45
Q

The only injectable Xa inhibitor

A

Fondaparinux

* THE BIGGER THE PERSON THE DOSES ARE HEFTIER

46
Q

Fondaparinux

REVERSAL

A
  • NO DIRECT REVERSAL

DOC: activated PCC (FEIBA)

47
Q

How many days do you avoid scheduled fibrinolytic or thrombolytics after neuraxial anesthesia?

A

10 days

48
Q

What is the ideal time for neuraxial procedure after cessation of fibrinolytics or thrombolytics?

A
  • ideal time for neuraxial procedures after cessation of fibrinolytics or thrombolytics is unknown, but the suggested time is 48 hours with documentation of normal coagulation studies
49
Q

How can you facilitate the assessment of neurologic function in patients that received emergent fibrinolytics and thrombolytics that have established continuous epidural catheters??

A

Minimize the administration of local anesthetics

50
Q

Guidelines for IV unfractionated heparin and neuraxial anesthesia

A
51
Q

SubQ heparin how long do you wait before you start manipulating catheters?

A

4- 6 hours

52
Q

SubQ LMWH how long do you wait before manipulating catheters

A

12 hours

53
Q

Recommendation for Factor Xa inhibitors and neuraxial anesthesia

Fondaparinux

A
  • Avoid indwelling neuraxial catheters and use single needle pass taking care not to have traumatic needle placement while on fondaparinux (grade 1C)
  • Wait at least 6 hours after catheter removal to start fondaparinux (grade 2C)
54
Q

Neuraxial anesthesia recommendation with Warfarin

A
  • Wait at least 5 days after the last dose of warfarin and ensure normalized INR before neuraxial anesthesia (grade 1B)
  • Minimize the administration of local anesthetics through established continuous epidural catheters in patients on concurrent warfarin to facilitate assessment of neurologic function (grade 1C)
  • INR must be checked daily if warfarin is continued with an indwelling epidural catheter (grade 2C)
  • Remove neuraxial catheter when INR is < 1.5
  • Indwelling neuraxial catheters may be kept with extreme caution in patients with INRs 1.5-3 (grade 2C)
  • If INR is > 3, stop warfarin or reduce dose while the catheter is in place (grade 1A). No recommendations can be provided regarding when to remove the catheter in this scenario (grade 2C)
55
Q

Neuraxial anesthesia recommendation with Direct Thrombin inhibitors and neuraxial anesthesia

A

Bivalrudin and Argatroban – >> NO!

56
Q

Recommendations to hold before surgery

A
57
Q

NOAC and impending surgical procedures

recommendations to hold before surgery

A
58
Q

What are antiplatelet agents

A
59
Q

Antiplatelets that are prodrugs

A
  • Clopidogrel
  • Prasugrel
60
Q

Antiplatelet that is reversible

A

TICAGRELOR

61
Q

What is the % platelet inhibition of

ASPIRIN

A

20 %

62
Q

What is the % platelet inhibition of

CLOPIDOGREL

A

40 %

63
Q

What is the % platelet inhibition of

PRASUGREL

A

70 %

64
Q

What is the % platelet inhibition of

TICAGRELOR

A

95%

65
Q

What is a drug that is not recommended for people with a history of stroke/ TIA

A

black box warning: Prasugrel

WARNING: AGE > 75

WEIGHT < 60 kg

66
Q

antiplatelet that may cause bradycardia SE

A

Ticagrelor

—> should not be given with aspirin >100 mg daily

67
Q

IV antiplatelet drug

how long before it restores platelet function after discontinuation?

A

CANGRELOR

–> practice: depending on whatever oral antiplatelet you decide there is a variety of loading mechanisms

68
Q

MOA of GP IIb/ III a inhibitors

A

GP IIb/IIIa inhibitors

  • Inhibits cross linkage of fibrinogen (final step in common hemostatic pathway for platelet aggregation)
  • Tirofiban, eptifibatide
  • Commonly used to manage acute coronary syndrome
  • Monitoring – ACT
  • Reversed by clearance of drug (short half life - ~20-40 min)
69
Q

Reversal of antiplatelet agents

A

tons of bleeding: platelet transfusion

  • If given, ideal to administer after 3-5 terminal half-lives of the antiplatelet to avoid pharmacologic inhibition of the transfused platelets
70
Q

Reversal of antiplatelet agents

Desmopressin

A

Increases endothelial release of factor VIII and von Willebrand factor and may increase platelet membrane glycoprotein expressionàpromotes platelet adhesion to endothelium

71
Q

When do you stop antiplatelets

impending surgical procedures

A
72
Q

Tx for High-risk patients and impending surgical procedure

A

Anesthesia Pharm (25 decks)

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