Pharm #1 - Antithrombolytics I and II

Question 1

What is the mechanism of action of heparin?

How is it monitored?

Route of administration?

Answer 1

Complex with AT(antithrombin) and inhibits factors Xa and IIa. (thrombin)

Monitored by APTT
(2-2.5 baseline therapeutic)

IV & Subcutaneous

(oral only for warfarin)

Question 2

What is the indication for heparin?

Answer 2

SURGICAL ANTI-COAGULATION! (only one indicated for this)

Question 3

What are the adverse effects of heparin (4)

2 major

Answer 3

1. bleeding
2. HIT (heparin induced thrombocytopenia)
3. osteoporosis
4. alopecia

Question 4

LMW Heparins
(branded and generic)

1. MOA
2. How is it monitored
3. Route

Answer 4

1.Complex with AT
inhibits factors Xa and IIa

2. monitored by anti-Xa
3. Subcutaneous

Question 5

LMW Heparins
(Enoxaparin or Lovenox)

Indications?

Adverse effect?

Differences with heparin? (2 main, 2 others)

Answer 5

prophylaxis and tx. of DVT and ACS

BLEEDING

1. better bioavailability!!
2. Longer duration of action (6 hours)
3. Less bleeding
4. Less thrombocytopenia

Question 6

What are the names of the heparin anticoagulants? (5)

Heparin antagonist?

Answer 6

Heparin & LMW Heparin

1. Argatroban
2. Bivalirudin
3. Hirudin
4. Fondaparinux (pentasaccharide)
5. Antithrombin Concentrate

Protamine Sulfate - heparin antagonist

Question 7

MOA for Fondaparinux (Pentasaccharide)

Route of administration?

Indication?

Answer 7

Complex with AT and inhibits factor Xa

• Subcutaneous
• Management of DVT

Question 8

Adverse effect of Fondaparinux

Answer 8

BLEEDING

• same for argatroban, bivalirudin, hirudin

Question 9

What is the MOA of argatroban, bivalirudin, hirudin, and Antithrombin concentrate?

How are they all administered?

Answer 9

Directly inhibits IIa (thrombin - they all inhibit thrombin!)

IV!!! (same with LMW Heparins)

Question 10

State the MOA of Argatroban

Route?

Indications?

Adverse effect?

Answer 10

1. inhibits IIa (thrombin)
2. IV
3. Anticoagulant
   - management of HIT
4. BLEEDING

Question 11

State the following for argatroban, bivalirudin, hirudin:

1. Route of admin
2. MOA
3. Indication
4. Adverse effect

Answer 11

1. Route = IV
2. MOA = inhibits IIa (thrombin)
3. Anticoagulant
   - management of HIT
4. Adverse - BLEEDING

Question 12

State the following for Antithrombin Concentrate:

1. Route of admin
2. MOA
3. Indications (4)
4. Adverse effect

Answer 12

1. IV
2. Inhibits IIA (thrombin)

3. 
DIC
Sepsis
Thrombophilia
hypercoaguable state

4. NO ADVERSE EFFECTS

Question 13

What drug has the following indications

DIC
Sepsis
Thrombophilia
hypercoaguable state

Answer 13

ANTI - THROMBIN CONCENTRATE!!!

• big gun!!

Question 14

What is the MOA of protamine sulfate?

How is it administered?

Indication?

Answer 14

HEPARIN ANTAGONIST

• IV
• Reversal for heparin

Question 15

What are the 2 major adverse effects of protamine sulfate?

Answer 15

1. Bradycardia

2. Hypotension

Question 16

MOA of Warfarin (2)

Answer 16

• competitive antagonist of vitamin K

- suppresses the synthesis of factors 2,7,9,10

Question 17

How is warfarin monitored?

What are the 2 indications?

Answer 17

1. PT/ INR
2. Prolonged treatment of DVT
3. Atrial Fibrillation

Question 18

What are the side effects of warfarin? (3)

Answer 18

• bleeding
• coumadin induced necrosis
• INTERACTION WITH SEVERAL MEDICATIONS (since it is highly protein bound) which results in bleeding due to the potentiating effect of warfarin

Question 19

MOA of vitamin K

monitoring?

Answer 19

• Cofactor in the synthesis of functional forms of factors:

2, 7, 9 , 10

(inhibited by warfarin)

2. monitoring NOT REQUIRED

Question 20

What are the indications of vitamin K?

Answer 20

1. Hypoprothrombinemia
2. Intestinal disorders
3. Gastrectomy
4. reverses the effects of WARFARIN
   - which is why patients are advised NOT to eat green leafy vegetables

Question 21

What is the main side effect of Vitamin K

Answer 21

Hemolysis

Question 22

Oral Anti-Xa

What are the 3 drugs in this category?

Answer 22

1. Rivaroxaban
2. Apixaban
3. Edoxaban

• all 3 have “exo & all inhibit Xa!!’

Question 23

What is the MOA of

1. Rivaroxaban
2. Apixaban
3. Edoxaban

Answer 23

Inhibits factos Xa

Question 24

For what is monitoring not required? (because there is no available monitoring)

Answer 24

1. Vitamin K
2. Rivaroxaban
3. Apixaban
4. Edoxaban

Question 25

What are the Indication for the Oral Anti-Xa agents? 1. Rivaroxaban 2. Apixaban 3. Edoxaban What is Rivaroxaban approved for?

Answer 25

Stroke prevention in patients with AF Ravaroxaban also approved for prophylaxis and tx. of DVT

Question 26

What is are the 2 major adverse effects of Oral Anti-Xa agents? 1. Rivaroxaban 2. Apixaban 3. Edoxaban

Answer 26

1. Bleeding 2. Liver toxicity! (same as Dabigatran - oral anti-thrombin)

Question 27

What is the MOA of Dabigatran?

Answer 27

Inhibits thrombin (IIa)

Question 28

How is Dabigatran monitored?

Answer 28

It is NOT monitored! | - no tests for Dabigtran

Question 29

What is the major indication for Dabigatran (Oral antithrombin)

Answer 29

Stroke prevention in patients with AF

Question 30

What are the major side effects of Dabigatran? (2)

Answer 30

Bleeding Liver toxicity

Question 31

Which drug has a duration of 1-2 hours and a half life that is dose dependent with a RAPID onset?

Answer 31

HEPARIN

Question 32

How is heparin metabolized? What has better bioavailability, heparin or LMW Heparins? Which is used for surgical anticoagulation (warfarin/hep); which is used for CHRONIC anticoagulation?

Answer 32

Metabolized by the LIVER, some by kidney (20-25%) - some picked up by mast cells 2. Low molecular weight heparins! - when given subcutaneously DOSED IN MG , not units like HEPARIN! 3. Surgical: heparin (no oral!) Chronic anticoagulation = warfarin (at war with your body!)

Question 33

Which drug is contraindicated in pregnant women?

Answer 33

WARFARIN - can cross placenta and cause bone & bleeding problems - All oral anticoagulants pass the placental barrier and may cause fetal bone malformation.

Question 34

What is hirudin used for? What is the commercial recombinant preparation called?

Answer 34

Direct Thrombin Inhibitor (DTI) used in patients that are heparin compromised hirudin keeps the blood flowing and prevents clots from forming! 2. REFLUDAN - used for anti-coagulant management for HIT patients

Question 35

What are the main factors that effect warfarin dose?

Answer 35

1. DIET - vitamin K can increase clotting - green leafy veggies (warfarin inhibits vitamin K synthesis) 2. LIVER - disease can result in a lower production of coagulation factors 3. DRUGS - aspirin is highly protein bound and can displace warfarin resulting in an increased INR and more anti-coagulation

Question 36

What is the principal toxicity of warfarin?

Answer 36

hypoprothrombinemia ecchymosis, purpura, hematuria, hemorrhage.

Question 37

What is coumadin skin necrosis?

Answer 37

the impairment of the functionality of protein C - This protein also requires gamma-carboxylation of glutamic acid for functionality (vitamin K dep) Protein C normally acts as an anti-coagulant by interacting with factors 5 and 8 inhibits their activation! Takes 48 hours before factor 7 begins to decrease after warfarin, but prior to this PROTEIN C decreases!!!!! - cannot act as an anti-coagulant by inhibiting factor 5 and 8 so acts as an additional phenomenon causing the blood to CLOT may result in HEMORRHAGIC LESIONS!

Question 38

What is the tx for coumadin skin necrosis/ oral anti-coagulant overdose?

Answer 38

1. Infuse factors 2,7,9,10 by giving fresh blood or frozen plasma 2. Recombinant factor 7a 3. Vitamin K

Question 39

Rivaroxaban and Apixaban, Edoxaban are cleared how? Which has less plasma protein binding than the rest?

Answer 39

1. R - RENALLY (65%) 2. Apixaban = 25% 3. Edoxaban - 35% renal (rest of drugs are LIVER) - are oral Anti-10a agents 4. EDOXABAN do not need to monitor if on these drugs BUT there is no test to monitor them!!!

Question 40

What is an anti-thrombin agent? How is it eliminated?

Answer 40

DABIGATRAN - RENAL elimination!!!! 100%

Question 41

What type of drugs are | Enoxaparin or Lovenox

Answer 41

LMW Heparins

Question 42

What is the difference between heparin and LMW heparin in terms of elimination kinetics?

Answer 42

Heparin is dose dependent LMW hep is dose independent and has a longer half life