L32 Heparin Anticoagulants II

Question 1

Broadly, which coagulation factors does heparin affect?

Answer 1

2a, 9a, 10a, 11a, 12a

Question 2

Broadly, which coagulation factors does warfarin affect?

Answer 2

2, 7, 9, 10

Question 3

Warfarin is an analogue and antagonist of ___.

Answer 3

Vitamin K

Question 4

What is the MOA of warfarin?

Answer 4

Depression of the formation of functional forms of factors 2, 7, 9, 10; this occurs via inhibition of the carboxylation of glutamic acid in these proteins which is essential for calcium binding; this occurs via inhibition of vitamin K formation via inhibition of vitamin K reductase/epoxide reductase

Question 5

Warfarin works in the ___, where coagulation factors are produced.

Answer 5

Liver

Question 6

What does a mutation in VKORC1 gene cause?

Answer 6

Lack of epoxide reductase

Question 7

Reduced/active vitamin K is used to convert the decarboxy form of ___ into the gamma carboxy form.

Answer 7

Prothrombin

Question 8

What is used to measure the extrinsic coagulation factors?

Answer 8

PT INR

Question 9

What is the order of reduction of Vitamin K dependent factors after warfarin administration?

Answer 9

7, 9, 10, 2

Question 10

As the coagulation factors decrease, the INR starts to ___.

Answer 10

Increase

Question 11

What is the 1st day of dosing for warfarin? The second day?

Answer 11

1st day: 5-10 mg/d

2nd day: 5-7 mg/d

Question 12

How is warfarin administered?

Answer 12

Orally only

Question 13

Describe the half life of warfarin.

Answer 13

Long (~36 hours) due to binding to plasma albumin (~99%)

Question 14

How is warfarin metabolized?

Answer 14

Hydroxylated to inactive compounds by the hepatic ER

Question 15

What is used to monitor the anticoagulant effects of warfarin?

Answer 15

Prothrombin time (PT/INR)

Question 16

What is considered therapeutic for warfarin?

Answer 16

A 1.5 time prolongation of the PT from the baseline

Question 17

Reagent based variations have been noted in PT. To obtain uniform degrees of anticoagulation, the concentp of INR has been introduced to adjust the level of anticoagulant in a given patient. INR = ?

Answer 17

(PT of patient/PT of mean normal control) x ISI

Question 18

What are 5 factors that affect the dose of oral anticoagulants?

Answer 18

1. Nutrition (diet high in vitamin K leads to a need for higher dose)
2. Anemia (need a higher dose due to dilution effect)
3. Liver disease
4. Biliary obstruction (less absorption, lower effect)
5. Drugs (increase or decrease effect)

Question 19

What are important drug interactions that cause potentiation?

Answer 19

1. Drugs that cause vitamin K deficiency (antibiotics)
2. Drugs that displace warfarin from protein binding sites
3. Drugs that decrease clotting-factor synthesis
4. Drugs that suppress or compete for microsomal enzymes
5. Drugs that have antiplatelet aggregating properties

Question 20

What are important drug interactions that cause inhibition of anticoagulant action?

Answer 20

1. Decreased warfarin absorption

2. Enhanced warfarin metabolism

Question 21

What is the principal toxicity of warfarin?

Answer 21

Hypoprothrombinemia (ecchymosis, purpura, hematuria, hemorrhage)

Question 22

Are oral anticoagulants contraindicated in pregnancy?

Answer 22

Yes

Question 23

Warfarin also produces necrosis - how?

Answer 23

Impairment of the functionality of protein C, which requires gamma-carboxylation of glutamic acid for functionality (lack of functional protein C decreases anticoagulant effect)

Question 24

How is oral anticoagulant overdose treated?

Answer 24

1. Replacement of the 4 factors with infusion of whole fresh blood or frozen plasma
2. Recombinant factor 7a
3. Vitamin K

Question 25

Compare and contrast heparin and warfarin vis a vis structure.

Answer 25

H: large acidic polymer W: small lipid-soluble molecule

Question 26

Compare and contrast heparin and warfarin vis a vis route of administration.

Answer 26

H: IV, SC W: Oral

Question 27

Compare and contrast heparin and warfarin vis a vis site of action.

Answer 27

H: Blood W: Liver

Question 28

Compare and contrast heparin and warfarin vis a vis onset of action.

Answer 28

H: rapid (seconds) W: slow, limited by half-lives of normal clotting factors

Question 29

Compare and contrast heparin and warfarin vis a vis MOA.

Answer 29

H: activates AT, which inhibits FXa and thrombin W: impairs synthesis of 2, 7, 9, and 10

Question 30

Compare and contrast heparin and warfarin vis a vis duration of action.

Answer 30

H: acute (hours) W: chronic (days)

Question 31

Compare and contrast heparin and warfarin vis a vis inhibition of coagulation in vitro.

Answer 31

H: yes W: n

Question 32

Compare and contrast heparin and warfarin vis a vis treatment of acute overdose

Answer 32

H: protamine sulfate W: IV vitamin K and fresh frozen plasma

Question 33

Compare and contrast heparin and warfarin vis a vis monitoring.

Answer 33

H: APTT W: PT/INR

Question 34

Compare and contrast heparin and warfarin vis a vis crossing of the placenta.

Answer 34

H: No W: Yes

Question 35

What is a naturally occurring fat soluble vitamin found in green vegetables and synthesized by gut flora?

Answer 35

Vitamin K

Question 36

What is the function of vitamin K?

Answer 36

Required for the synthesis of factors 2, 7, 9, and 10; essential to the attachment of a calcium binding functional group to prothrombin protein

Question 37

What is the therapeutic use of vitamin K?

Answer 37

Drug induced hypoprothrombinemia antidote, intestinal disorders and surgery, and hypoprothrombinemia of newborns

Question 38

What are the toxicities of vitamin K?

Answer 38

Non-toxic; high doses sometimes cause hemolysis in infants

Question 39

What are the new oral anti-10a agents?

Answer 39

Rivaroxaban, Apixaban, Edoxaban, Betrixaban

Question 40

What is the antidote to the anti-10a agents?

Answer 40

There isn't one as of right now

Question 41

What is the new oral anti-thrombin agent?

Answer 41

Dabigatran

Question 42

What is the antidote to dabigatran?

Answer 42

Idarucizumab

Question 43

What is the MOA of warfarin?

Answer 43

Competitive antagonist of vitamin K; suppresses the synthesis of 2, 7, 9, and 10 by blocking enzyme epoxide reductase in the liver

Question 44

What is the MOA of vitamin K?

Answer 44

Cofactor in the synthesis of 2, 7, 9, and 10

Question 45

What is the MOA of the oral anti-10a drugs?

Answer 45

Inhibits factor 10a

Question 46

What is the MOA of dabigatran?

Answer 46

Inhibits thrombin

Question 47

How are the oral anticoagulants monitored?

Answer 47

Warfarin: PT/INR | All others: not required

Question 48

What are the indications of warfarin?

Answer 48

Prolonged treatment of DVT and AFib

Question 49

What are the indications of Vitamin K?

Answer 49

Hypoprothrombinemia, intestinal disorders and gastrectomy, reverse warfarin effects

Question 50

What are the indications of the oral anti-10a's?

Answer 50

Stroke prevention in patients with AF (all); prophylaxis of DVt (R, A, B); acute coronary syndrome (R)

Question 51

What are the indications of dabigatran?

Answer 51

Stroke prevention in patients with AFib

Question 52

What are the side effects of warfarin?

Answer 52

Bleeding, coumadin-induced necrosis; interacts with several medications that can potentiate/inhibit effects; crosses placental barrier and causes birth defects

Question 53

What are the side effects of Vitamin K?

Answer 53

Hemolysis

Question 54

What are the side effects of oral anti-10a drugs?

Answer 54

Bleeding, liver toxicity (R, A, E)

Question 55

What are the side effects of dabigatran?

Answer 55

Bleeding, liver toxicity; cleared by kidney and could be problematic in patients with abnormal kidney function