Anticoagulants II Flashcards

1
Q

coumarin/Coumadin’s uses

A

Prophylactic use: Prevention of thrombotic disorders

Therapeutic use: Treatment of established thrombus

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2
Q

Coumadin inhibits which factors

A

factors II, VII, IX, and X

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3
Q

warfarin’s structure is similar to

A

vitamin K

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4
Q

warfarin/coumadin’s MOA

A

All agents depress the formation of functional forms of factors II (prothrombin), VII, IX and X by inhibiting the carboxylation of glutamic acid in these proteins which is essential for Ca+2 binding. (blocks vit k synthesis)

factors are still present but not functional

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5
Q

onset of warfarin/coumadin

A

long- takes 8 to 10 hours before the amount of active factors decreases, 3-5 days before a pt is properly anti-coagulated.

due to binding of albumin in the plasma

therefore it is not use when a pt presents to the ER with a thrombus but can be given for them to take afterwards at home

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6
Q

bioavailability of warfarin/coumadin

A

100%

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7
Q

metabolism of warfarin/coumadin

A

hydroxylated to inactive compounds by the hepatic endoplasmic reticulum.

varies greatly between patients therefore pts must be monitored

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8
Q

which pathway does warfarin/coumadin affect

A

extrinsic

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9
Q

what do you use to monitor warfarin/coumadins effects

A

Prothrombin time (PT)/INR

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10
Q

what deviation from baseline is needed for warfarin to be in the therapeudic range

A

a PT of 1.5 times baseline

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11
Q

INR

A

Reagent based variations have been noted in the prothrombin time. To obtain uniform degrees of anticoagulation, the concept of international normalized ratio (INR) has been introduced.

The INR can be used universally to adjust the level of anticoagulant in a given patient. Thus it helps in the optimization of dosage .

ratio of the patients PT divided by the mean normal control

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12
Q

what are some factors that affect the dose of warfarin/coumadin that you want to give a patient

A
Nutrition
Anemia
Liver disease 
Biliary obstruction
Drugs
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13
Q

how does diet affect warfarin

A

green leafy vegetables high in vitamin K decrease the affects of warfarin/coumadin

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14
Q


 how do Drugs cause warfarin potentiation

A

by causing vitamin K deficiency.
by displacing warfarin from protein binding sites.
by decreasing clotting-factor synthesis.
by suppressing or competing for microsomal enzymes.
by having antiplatelet aggregating properties.

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15
Q

how do drugs cause inhibition of the anticoagulant action of warfarin

A

by decreasing warfarin absorption.

by enhancing warfarin metabolism.

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16
Q

Toxicity of Warfarin

A
  • hypoprothombinemia resulting in ecchymosis, purpura, hematuria, hemorrhage.
  • All oral anticoagulants pass the placental barrier and may cause fetal malformation

necrosis (due to non-functionality of protein C)

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17
Q

how is protein C affected by warfarin and how does this affect the patient

A

protein C non-functioning in the presence of warfarin. functional protein C’s levels drop before the other factors. Because protein C is an anticoagulant and inhibits factors V and VII, initially there is an increased tendency to clot

18
Q

Treatment of oral anticoagulant overdose

A
  1. Replacement of 4 factors. Infusion of whole fresh blood or frozen plasma.
  2. Recombinant Factor VIIa
  3. Vitamin K
19
Q

Function of Vitamin K

A

Essential to the attachment of a calcium binding functional group to prothrombin protein (presence of γ carboxyglutamic acid).

Required for the synthesis of clottable coagulation factors (II, VII, IX and X).

20
Q

Therapeutic use of Vitamin K

A

Drug induced hypoprothrombinemia antidote.
Intestinal disorders and surgery (gastrectomy).
Hypoprothrombinemias of newborn.

21
Q

toxicity of Vitamin K

A

Very non-toxic

High doses sometime cause hemolysis in infants (mainly water soluble vitamin K).

Certain individuals who are sensitive to primaquine may develop hemolysis.

22
Q

anti Xa agents

A

Rivaroxaban (Xarelto)

Apixiban

23
Q

Antithrombin Agent

A
  • Dabigatran
24
Q

characteristics of new oral anticoagulants (anti-Xa and antithrombin)

A

given orally

mono-therapeudic drugs

25
Q

oral anticoagulants (anti-Xa and antithrombin) uses

A

stroke prevention in people who previously had a DVT

or treatment of a DVT

26
Q

advantages and disadvantages of oral anticoagulants (anti-Xa and antithrombin)

A

they do not need to be monitored but also a disadvantage is you cannot monitor them therefore is emergency surgery is needed you do not know how much is present.

27
Q

rivaroxaban target

A

factor Xa

28
Q

rivaroxaban dosing

A

fixed once per day

29
Q

rivaroxaban monitoring

A

no

30
Q

rivaroxaban clearence

A

65% renal

31
Q

rivaroxaban interactions

A

potent CYP3A4 inhibitors

32
Q

Apixiban target

A

factor Xa

33
Q

apixiban dosing

A

fixed 2 time per day

34
Q

apixiban clearence

A

25% renal

35
Q

apixiban interactions

A

potent CYP3A4 inhibitors

36
Q

Dabigatran target

A

factor IIa (thrombin)

37
Q

dabigatran dosing

A

fixed 2 times per day

38
Q

dabigatran clearence

A

100% renally (dont give to pts with renal failure)

39
Q

dabigatran drug interactions

A

proton pump inhibitors

40
Q

warfarin clearence

A

hepatic (none renally)