Pharmacology of Oral Anticoagulants 2

Question 1

What are advantages of DOACs

Answer 1

No routine monitoring, rapid onset, fixed dosing

Question 2

What are the DOACs

Answer 2

Dabigatran, Rivaroxaban, Apixaban, Edoxaban

Question 3

Which of the DOACs is a prodrug

Answer 3

Dabigatran

Question 4

What are characteristics of Dabigatran

Answer 4

Selective,relative, direct thrombin II inhibitor, fixed dose, favors drug dissolution in a acidic environment but preservers gut absorption even when gastric pH is high

Question 5

What converts dabigatran into the active form

Answer 5

esterases in the plasma and the liver

Question 6

What is the onset and half life of Dabigatran

Answer 6

2-3 hours, 12-17 hours

Question 7

T/F: Food affects bioavailability and peak plamsa concentrations of Dabigatran

Answer 7

False: Food does NOT affect the bioavailabiltiy of dabigatran but delays time of peak plasma concentrations by 2 hours

Question 8

How is Dabigatran eliminated through the body, how does this affect those with certain impairments

Answer 8

90-95% eliminated in the urine unchanged, moderate or severe decline in renal function may prolong excretion rates, elevate plasma concentrations, and increase half life

Question 9

T/F: Dabigatran is metabolized by CYP 450

Answer 9

False: Dabigatran is NOT metabolized by CYP 450

Question 10

What medical treatment could possibly remove Dabigatran

Answer 10

Hemodialysis

Question 11

T/F: INR cannot be used to change the dose of Dabigatran

Answer 11

True

Question 12

What are the contraindications for Dabigatran

Answer 12

Active pathological bleeding, serious hypersensitvity reactions

Question 13

What is the dosing for Dabigatran in DVT and PE

Answer 13

5-10 days of parental anticoagulation then 150 mg twice daily (can’t be given if CrCl is less than 30)

Question 14

What type of drugs should be avoided when someone is taking Dabigatran

Answer 14

Pg-p inducers and inhibitors

Question 15

What are Pg-p inducers, what happens when co-administered with Dabigatran

Answer 15

Rifampin, Avasimibe, Carbamazepine, Phenytoin, St. John’s wort, Tipranavir/ritonavir/ reduce drug concentration and increase risk of failure

Question 16

What are Pg-p inhibitors, what happens when co-administered with Dabigatran

Answer 16

Dronaderone and Ketoconazole/ an increased risk of bleeding

Question 17

What is the age that puts adults at higher risk of bleeding, side effect that should be discussed

Answer 17

Greater than 75 years, Dyspepsia

Question 18

T/F: Because dabigatran cannot be actively tested it is important to emphasize that a patient is adherent to the medication

Answer 18

True

Question 19

Which DOAC is a selective, reversible direct inhibitor of Factor Xa

Answer 19

Rivaroxaban (Xarelto)

Question 20

What are important characteristics of Rivaroxaban (Xarelto)

Answer 20

Doesn’t require a cofactor (such as anti-thrombin III) for activity, by inhibiting FXa decreases thrombin generation, no direct affect on thrombin aggregation but indirectly inhibits platelet aggregation induced by thrombin

Question 21

What is unique about rivaroxaban bioavailability, how

Answer 21

Dose dependent/ 10 mg dose not affected by food, higher than 10 mg it must be taken with food to increase Cmax and mean AUC

Question 22

T/F: Rivaroxaban is affected by P-gp drugs and is highly protein bound at over 90%

Answer 22

True

Question 23

What is Rivaroxaban metabolized by

Answer 23

CYP 3A4

Question 24

What is the dosing for Rivaroxaban for treatment of DVT and/or PE

Answer 24

15 mg twice a day with food for 21 days followed by 20 mg once daily with food for the remaining treatment

Question 25

What is the dosing for Rivaroxaban for reduction in the risk of recurrence of DVT and/or PE in patients at continued risk for DVT and/or PE,prophylaxis of DVT after hip or knee surgery

Answer 25

10 mg with or without food daily

Question 26

What DOAC is a selective inhibitor of Factor Xa

Answer 26

Apixiban (Eliquis)

Question 27

T/F: Apixiban also does not require antithrombin 3 activity and does not use INR/PT for dose adjustments

Answer 27

True

Question 28

T/F: Just like Rivaroxaban, Apixiban bioavailabilty is affected by food

Answer 28

False: Apixiban bioavailability is not affected by food

Question 29

How is Apixiban metabolized, protein binding

Answer 29

CYP 3A4, around 87%

Question 30

What are drug interactions that Apixiban (Eliquis) has that increase concentration, how can this be alieviated

Answer 30

Ketoconazole, Itraconazole, Ritonavir/Reduce dose by 50%

Question 31

What are drug interactions that Apixiban (Eliquis) has that decrease concentration

Answer 31

Rifampin, Barbiturates, Carbamezapine. Phenytoin, St. John’s Wort

Question 32

What is the least popular Factor Xa inhibitor

Answer 32

Edoxaban (Savaysa)

Question 33

What is Edoxaban peak, bioavailability, and half life

Answer 33

1-2 hours, 62%, 10-14 hours

Question 34

What is a unique contraindication for using Edoxaban

Answer 34

Cannont be used if CrCl is greater than 95

Question 35

Which DOAC is approved for patients hospitalized with an acute medical illness who are at risk for VTE

Answer 35

Betrixiban

Question 36

Which DOACs need a parenteral lead in

Answer 36

Dabigatran and Edoxaban

Question 37

Which DOACs have a dosing frequency of once a day, which starts off as twice a day

Answer 37

Rivaroxaban and Edoxaban, Rivaroxaban

Question 38

T/F: DOACs and Warfarin should never be used while a patient is pregnant or breastfeeding

Answer 38

True

Question 39

Which DOAC cannot be crushed and mixed with food

Answer 39

Dabigatran

Question 40

What is the reversible agent for Dabigatran/ Rivaroxaban, Apixaban, Edoxaban

Answer 40

Idarucizumab/Andexanet alfa

Question 41

When using DOACs what values should be monitored

Answer 41

CBC, Scr, Drug-drug interactions