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Practical Therapeutics 1 > Anticoagulants > Flashcards

Anticoagulants Flashcards

1
Q

Warfarin use compared to other anticoagulants

A

inhibits the synthesis of clotting factors

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2
Q

anticoagulants function

A

all but warfarin inhibit the activity of clotting factos

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3
Q

where do venous thrombi occur

A

at sites where blood flow is low - stagnation of blood flow initiates the clotting cascade

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4
Q

Classes an anticoagulants

A

1) vitamin k antagonist
2) antithrombin activators
3) direct thrombin inhibitors
4) direct Xa inhibitors

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5
Q

Warfarin (coumadin/ jantoven) indications

A

MI, thromboembolic complications (PE, DVT, afib, CARDIAC VALVE REPLACEMENT)

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6
Q

US box warnings for Warfarin (coumadin/ jantoven)

A
  • bleeding risk

- monitor INR on all treated patients

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7
Q

MOA of Warfarin (coumadin/ jantoven)

A

Inhibits the synthesis of certain clotting factors
2,7,9,10 and protein c and s via inhibiting vitamin K epoxide reductase complex 1 and decreasing activation of the factors
- essentially a VITAMIN K ANTAGONIST

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8
Q

ADR OF Warfarin (coumadin/ jantoven)

A

BLEEDING (<5% when INR is 4 or less)

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9
Q

metabolism / excretion of Warfarin (coumadin/ jantoven)

A

1) adjusting dose in kidney function may need to happen- no robust guidelines - 10/20% reduction in eGFR <60
2) liver function plays a significant role in anticoagulant response - monitor INR closely

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10
Q

routes of Warfarin (coumadin/ jantoven)

A

oral

- color coordinated!

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11
Q

Warfarin (coumadin/ jantoven) contraindications (7)

A

1) hemorrhagic tendencies- active GI bleed or ulceration, respiratory or GU tract bleed
2) recent or potential surgery on spine or eyes
3) malignant, uncontrolled HTN
4) pericarditis or pleural effusion
5) bacterial endocarditis
6) patients with high potential for non compliance
7) pregnancy/breast feeding

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12
Q

Regular INR, warfarin normal INR, and warfarin INR for those after cardiac valve replacement

A

1 = normal
2-3 = regular usage
2.5-3.5 = cardiac valve replacement (for most of them)
- Most patients we will start them in the hospital. Most patients with Warfarin are seen on an every 4 week basis

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13
Q

Vitamin K, Phytonadione Indications

A

1) hemorrhage prevention in newborns (intracranial) - single dose of injectable phytonadione immediately after delivery supported by AAPA
2) warfarin antidote- reverses hypoprothrombinemia and bleeding (preoperatively or in the case of severe bleeds)

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14
Q

MOA of Vitamin K, Phytonadione

A

required for synthesis of prothrombin (PT) and clotting factors 7,9,10 (vitamin k dependent factors) and are essential for the coagulation cascade

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15
Q

Route Vitamin K, Phytonadione

A

oral tablets are expensive

can be IV/Im

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16
Q

ADR Vitamin K, Phytonadione

A

essentially there is no storage- metabolism and secretion can occur rapidly

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17
Q

how is Vitamin K obtained

A

in the diet and synthesized by the normal gut flora

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18
Q

food interaction with warfarin

A
  • vitamin k containing foods decrease INR and effects (leafy greens, mayo)
  • foods increase the effects- alcohol, cranberries, cherries, and grapefruit
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19
Q

Drug interactions with Warfarin

A
  • interactions can increase effectiveness (more bleeding) or decrease (more clotting)
  • in general interactions of long term drugs can be managed by adjusting dosing
  • acute use drugs need to be weighed carefully
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20
Q

notable drug interactions with warfarin (3)

A

1) SULFA-ANTIBIOTICS (most important)- displace warfarin on albumin - significant bleeding risk (bactrim)
2) tylenol- used to be considered safe and NSAIDs/ASA weren’t , now shown to increase INR
3) carbamazepine, phenobarbital and rifampin - powerful induces in CYP stream and DECREASE THE EFFECTS

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21
Q

Warfarin clinical pearls

A
  • in patients with new onset DVT/PE or other active clots, warfarin is started at the same time as parenteral anticoagulate and is continued for a MINIMUM of 5 DAYS AND until the INR is greater or equal to 2 for 24 hours
  • CHEST guidelines now recommend apixaban, rivaroxaban, dabigatran or edoaban (NOACS, novel oral anticoagulants) over warfarin for DVT / PE (non cancer) and LMWH over warfarin
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22
Q

heparin (unfractionated heparin ) indications

A

1) anticoagulation - prophylaxis and treatment of thromboembolic disorders, preventing of clotting in arterial and cardiac sx, anticoagulation for blood tx, extracorporeal circulation and dialysis procedures

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23
Q

heparin (unfractionated heparin) MOA

A

potentiates the action of antithrombin III- inactivating thrombin and factor Xa- prevents conversion of fibrinogen to fibrin (clot formation )

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24
Q

contraindications of heparin (unfractionated heparin)

A

severe thrombocytopenia, history of HIT, and uncontrolled active bleeding

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25
Q

Routes heparin (unfractionated heparin)

A

1) iv (full dose, treatment dose) -algorithim based following anti-Xa or activated partial thromboplastin time (aPTT) levels
- bolus- given if effect is needed immediately
2) subQ
- 5000 mg q8-12
- 7500 mg q12 for obese

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26
Q

ADR heparin (unfractionated heparin)

A

1) bleeding and thrombocytopenia

2) localized reactions in subQ administration- bruising, irritation, hemotoma

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27
Q

metabolism/ excretion heparin (unfractionated heparin)

A

onset of action- within MINUTES of IV administration

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28
Q

doses of heparin (unfractionated heparin)

A

1) IV - full dose based on aPTT
give bolus now and then follow up with a continuous fusion (give to someone with an active clot)
2) subQ (prophylaxis)
5000 units q8-12h or 7500 units q8h in morbidly obese)

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29
Q

Heparin induced thrombocytopenia

A
  • potentially fatal immune mediated disorder- results in rapid platelet count drops and potentially a paradoxical INCREASE in clotting
  • antibodies are developed against heparin platelet complexes causing damage to the vascular endothelium - increases clotting and decreasing platelets
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30
Q

heparin induced thrombocytopenia confirmatory test

A

heparin platelet factor 4 antibody test (PF4 ELISA) and serotonin release assay (SRA)

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31
Q

what do you use when HIT is confirmed/ suspected

A

argatroban

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32
Q

protamine indications

A

heparin neutralization

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33
Q

US box warnings protamine

A

hypersensitivity reactions

34
Q

MOA of protamine

A
  • forms a stable salt with heparin and nullifies anticoagulant activity
  • protamine is an alkaline, positive charged molecule, heparin is an acidic negatively charged molecule
35
Q

route of protamine

36
Q

ADR of protamine

A

1) bradycardia
2) flushing
3) hypotensioin

37
Q

What is enoxaparin

A

Lovenox or low molecular weight heparin (LMWH)

38
Q

Enoxaparin (lovenox) indications

A

ACS, DVT/PE, VTE prophylaxis

39
Q

us box warnings Enoxaparin (lovenox)

A

spinal and epidural hematoma

40
Q

MOA Enoxaparin (lovenox)

A

shortened derivative of heparin- has anti Xa and antithrombin activity- enoxaparin has more Xa than thrombin inactivation

41
Q

Enoxaparin (lovenox) contraindications

A

history of HIT, active major bleeding

42
Q

route Enoxaparin (lovenox)

43
Q

ADR Enoxaparin (lovenox)

A

anemia or hemorrhage

44
Q

Enoxaparin (lovenox) compared to heparin

A

LMWH are heparin preparations composed of molecules that are shorter than those found in unfractionated heparin

  • in general, they are as effective, but they are easier to administer, and they require less stringent monitoring and can be given in fixed dosing
  • it has a longer half life
45
Q

Doses of Enoxaparin (lovenox) *****

A

1) full - 1mg/kg q 12h or 1.5 mg/kg q24h
2) prevention/ prophylaxis - 40mg q24h or 30mg q12h
3) intermediate dosing - 60 mg q12h or 1mg/kg q 24h (COVID)

46
Q

Fondaparinux indications

A
  • DVT/PE treatment, VTE prophylaxis
  • does not promote HIT, although it can lower platelets
  • can be used in patient with HISTORY of HIT, but in active HIT, argatroban is used
47
Q

us box warnings Fondaparinux

A

spinal and epidural hematomas

48
Q

MOA of Fondaparinux

A

selevtive indirect inhibition of factor Xa- NO activity against thrombin

49
Q

Fondaparinux contraindications

A

1) severe renal impairment
2) body weight <50kg
3) active major bleeding
4) bacterial endocarditis

50
Q

ADR Fondaparinux

A

anemia and bleeding

51
Q

Argatroban indications

A

prophylaxis or treatment of thrombosis in patients with HIT or hx of HIT; anticoagulant for PCI in patients with HIT or hx of HIT

52
Q

moa Argatroban

A

direct inhibition of thrombin

53
Q

contraindications Argatroban

A

major bleeding

54
Q

ADR Argatroban

A

bleeding and hypotension

55
Q

metabolism/ excretion Argatroban

A

dosed off of bilirubin and monitored with aPTT

56
Q

Bivalirudin indications

A

anticoagulant used in patients undergoing primary PCI or PCI facilities

  • given in combo with ASA and PSY12 inhibtior
  • similar to heparin but more expensive
57
Q

contraindications of Bivalirudin

A

active major bleeding

58
Q

MOA Bivalirudin

A

direct thrombin inhibitor

59
Q

ADR Bivalirudin

A

1) bleeding

2) hypotension (about 1/3 amount of major bleeding as heparin)

60
Q

dabigatran indications

A

DVT/ PE treatment and prevention
a fib
VTE prophylaxis in total hip arthoplasty

61
Q

US box warning dabigatran

A

1) thrombotic events- premature d/c increases risk of thrombotic events
2) spinal/ epidural hematoma

62
Q

MOA dabigatran

A

direct thrombin inhibitor - dabigatran etexilate (prodrug) undergoes rapid conversion to active drug pradaxa

63
Q

Contraindications dabigatran

A

1) active bleeding

2) PATIENTS WITH MECHANICAL HEART VALVES (RE-ALIGHN TRAIN SHOWED MORE STROKES)

64
Q

ADR dabigatran

A

1) bleeding - many lawsuits
2) GI disturbance

remember dabigatran is pradaxa

65
Q

Direct factor Xa inhibitors indications

A

afib, vte treatment and prophylaxis, vte prophylaxis in hip and knee arthoplasty

66
Q

us box warnings Direct factor Xa inhibitors

A

1) premature d/c increases risk of thrombotic events

2) spinal/epidural hematoma

67
Q

MOA Direct factor Xa inhibitors

A

selective direct inhibition of factor Xa- inhibits production of thrombin

68
Q

contraindication Direct factor Xa inhibitors

A

active bleeding

69
Q

Direct factor Xa inhibitors ADR

A

Bleeding (all other agents > rivaroxaban apixaban)

70
Q

Rivaroxaban (xarelto) additional indications

A

stable CAD to reduce risk of CV events, PAD to reduce risk of thrombotic events, VTE prophylaxis in acutely ill

71
Q

dosing Rivaroxaban (xarelto)

A

VTE - 15 mg BID x 21 days then 20 mg with evening meal

Afib- 20 mg with evening meal

CAD/PD - 2.5 mg bid

72
Q

Apixaban (eliquis) dosing

A

1) afib - 5 mg bid

2) vte - 10 mg bid x 7 days, then 5 mg bid

73
Q

edoxaban (savaysa) contraindications

A

Use not recommended if CrCL > 95 ml/min

-if you have really good kidney function it is generally not recommended

74
Q

What are the three drugs that are direct factor Xa inhibitors?

A

1) rivaroxaban (xarelto)
2) apixaban (eliquis)
3) Edoxaban

75
Q

Thrombolytic (fibrinolytic) - lytics
Clot Busters
Uses

A
  • Given to remove thrombi that have ALREADY FORMED - as opposed to anticoagulants and antiplatelets which are preventing the formation of thrombi
  • Use: (acute, serious events)
    1) acute MI
    2) massive PE (saddle-PE)
    3) acute ischemic stroke
76
Q

Three thrombolytic agents

A

1) alteplase
2) tenecteplase
3) retaplase

77
Q

ADR for thrombolytics (Fibrinolytics)

A

All pose a risk of serious life threatening bleeding- HIGHEST AMONG ALL ANTI-THROMBOTIC DRUGS

78
Q

Alteplase indications

A

1) ACUTE ISCHEMIC STROKE

2) PE

79
Q

Alteplase MOA

A

inititates fibrinolysis by converting plasminogen to plasmin in a thrombus that results in dissolution of the clot

80
Q

Alteplase two names and uses

A

1) Activase - more expensive and for PE and acute ischemic stroke
2) Cathflo- used for occlusion of catheters and much cheaper

81
Q

ADR for alteplase

Practical Therapeutics 1 (10 decks)

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