Anticoagulants

Question 1

Dabigatran

Answer 1

MOA: Direct thrombin inhibitor that acts at factor 2
Dosing: BID
PK: renal elimination with t1/2 of 12-17 hours

Question 2

Bivalirudin

Answer 2

MOA: Direct thrombin inhibitor that acts at factor 2
Dosing: IV
PK: proteolytic elimination with t/12 of 25 min

Question 3

Argatroban

Answer 3

MOA: Direct thrombin inhibitor that acts at factor 2
Dosing: IV
PK: hepatic elimination with t1/2 of 40-50min

Question 4

Rivaroxaban

Answer 4

MOA: Factor 10a inhibitor
Dosing: daily or BID
PK: hepatic elimination with t1/2 of 5-9 hours

Question 5

Apixaban

Answer 5

MOA: Factor 10a inhibitor
Dosing: BID
PK: hepatic elimination with t1/2 of 12 hours

Question 6

Edoxaban

Answer 6

MOA: Factor 10a inhibitor
Dosing: once a day
PK: hepatic and renal elimination with t1/2 of 10-14 hours
Note: less effective when CRCL>95

Question 7

What is the complex mechanisms of UFH?

Answer 7

1. allosteric activation of ATIII (specific 5-saccharide sequence required)
2. ternary complex formation with ATIII and thrombin (min 18-saccharide chain required) for thrombin inhibition

Question 8

What can UFH (using heparin) cause?

Answer 8

Heparin induced thrombocytopenia where it leads to platelet activation–> consumption–> thrombosis

Question 9

What are other properties of UFH?

Answer 9

1. High binding to other targets which can lead to side effects and change in monitoring (HIT, PTT monitoring, osteopenia)
2. Cleared by reticuloendothelial system which causes shorter t1/2 than LMWH and no need for renal dose adjustment

Question 10

Low molecular weight heparins: enoxaparin and dalteparin

Answer 10

MOA is similar to heparin (complex) but decreased inhibition of thrombin (chain less than 18) which causes less effect on PTT

Question 11

What are other properties of LMWH?

Answer 11

1. Decreased binding to other targets which causes lower incidence of HIT and more consistent half life
2. Requires renal dose adjustment because longer half life
3. More consistent anticoag effect so less monitoring

Question 12

Fondaparinux

Answer 12

MOA: synthetic 5-saccharide analog that inhibits factor Xa only (no thrombin inhibition)
Drug monitoring: similar to LMWH
PK: renally cleared with long half life (once a day dosing)
Benefits: does not cause HIT
Downsides: not reversed by protamine like UFH

Question 13

Warfarin

Answer 13

MOA: Vit K dependent clotting factor (inhibits factors 2, 7, 9, 10, S, C) and inhibits VKOR to lower vitamin K
Onset: after day 2-4 INR begins to rise (d/t lower factor VII,) then after day 5 anticoagulation is achieved since X then eventually II are lower
Stereoisomers: S has stronger VKOR inhibitor and metabolized by CYP 2C9

Question 14

What are side effects and CIs of warfarin?

Answer 14

Side effects: More bleeding and skin necrosis (purple toe syndrome)
CI: pregnancy

Question 15

How do genetics effect warfarin?

Answer 15

• Reduce dose if carry one or both VKORC1 variant d/t increased sensitivity (25% for hetero and 50% for homo)
• Reduce dose if carry one or both CYP2C9 (25% for hetero and 50% for homo)

Question 16

What are drug interactions with warfarin?

Answer 16

1. Cyp inducers decrease INR and increase clotting (carbamazepine, phenytoin, rifampin, phenobarbital, chronic alcohol)
2. Cyp inhibitors increase INR and bleeding (amiodarone, fluconazole, acute alcohol)
3. Anticoags and antiplatelets increase risk of bleeding (aspirin, clopidogrel, LMWH)

Question 17

What categories makes a patient more sensitive to warfarin?

Answer 17

Acute illness or surgery, hyperthyroidism, decompensated HF, liver disease, malnourishment, low albumin, elevated baseline INR, low body weight

Question 18

What categories make a patient more resistant to warfarin therapy?

Answer 18

Hypothyroidism and higher body weight

Question 19

What does citrate do?

Answer 19

MOA: decreases calcium levels on the clotting factors like warfarin
Indications: anticoagulation of extracorpeal blood circuits
- Citrate infused after blood leaves and calcium infused as blood returns and requires monitoring with dose adjustments
- Also used for anticoag of blood stored for transfusion but if too much citrate= too much clotting and put calcium in it