Pharm: Heparin Anticoagulants Flashcards Preview

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Flashcards in Pharm: Heparin Anticoagulants Deck (51):
1

Describe where heparin is found naturally within the body

Found in mast cell granules with histamine and serotonin

2

Describe the chemical structure of heparin

Strongly acidic mucopolysaccharide with repeating units of sulfated glucuronic acid and sulfated glucosamine

3

Describe the size of heparin

Heterogenous
Molecular weight varies between 2kDa and 40kDa

4

What is the mechanism of action of heparin?

Inhibits action of Xa, IIa, XIIa, Xia (2,10,11,12)
by binding to ATIII and increasing ATIII affinity for these factors

5

What are the actions of heparin?

Plasma clearing
Neutralization of vascular lining
Release of tissue factor pathway inhibitor (TFPI)

6

What is the route of administration of heparin?

IV or subcutaneous
Not absorbed orally or rectally

7

How is heparin therapy monitored?

Heparin therapy is carefully monitored using APTT
Target APTT is 2-2.5x baseline

8

How is heparin metabolized?

25% excreted in urine
Some metabolized in liver by heparinases
Mast cells take up heparin
Endothelium binds heparin

9

Describe the pharmacokinetics of heparin

PK of heparin is dose dependent
Higher doses, longer half life

10

What are the endogenous modulators of heparin action?

ATIII
Heparin cofactor II
Tissue factor pathway inhibitor (TFPI)
Platelet factor 4 (PF4)

11

What are the side effects of heparin?

Hemorrhagic complications
Heparin induced thrombocytopenia
Osteoporosis --> fracture risk
Alopecia (loss of hair)

12

What are the clinical uses of heparin?

Therapeutic, surgical and prophylactic ANTICOAGULATION
Unstable angina
Adjunct therapy with thrombolytic drugs
Thrombotic and ischemic strokes

13

What is the antagonist of heparin?

Protamine: very basic protein derived from fish sperm
Combines with heparin to form stable salt with no anticoagulant activity
1:1 antagonism

14

Describe the structure of chemically synthesized heparin

Composed of pentasaccharide
Mimics the sequence repeats found in natural heparin in order to maintain ATIII interaction

15

How does the bioavailability of LMW heparin differ from native heparin?

LMW heparin has 100% bioavailability unlike native heparin which has ~30% bioavailability

16

What are the clinical advantages of LMW heparin

Better bioavailability, longer duration of action, less bleeding, lesser thrombocytopenia

17

What are the clinical uses of LMW heparin

DVT: Prophylaxis and treatment
Acute coronary syndromes management
Anticoagulation during procedures

18

What are antithrombin concentrates clinically used for?

Congenital antithrombin deficiency
Sepsis and DIC

19

What is hirudin?

A thrombin inhibitor derived from leaches
Used for anticoagulation in thrombocytopenic patients

20

What is argatroban?

A synthetic anti-thrombin agent used as an anticoagulant alternative to heparin for patients with heparin induced thrombocytopenia

21

What is bivalirudin?

A synthetic antithrombin that is a combination of hirudin and a tripeptide
used for anticoagulation during stent placement and angioplasty

22

What is fondaparinux?

Pentasaccharide
Complexes with ATIII in order to inhibit factor Xa
Used for management of DVT

23

What is the most common side effect of heparin and related drugs?

Bleeding

24

What is the mechanism of action of argatroban, bivalirudin and hirudin?

Directly inhibits IIa (thrombin)

25

What is the main oral anticoagulant prescribed in the US?

Warfarin

26

What are the clinical uses of warfarin?

Prophylaxis for thrombotic disorders
Treatment of established thrombus

27

What class of drugs does warfarin belong to?

Vitamin K antagonists (VKAs)

28

What coagulation factors does warfarin act on?

II, VII, IX, X

29

Warfarin is an analogue of _________

Vitamin K
Warfarin and Vit K have similar chemical structures

30

What is the mechanism of action of warfarin?

Inhibit II, VII, IX, X by preventing carboxylation of glutamic acid, thus preventing Ca2+ binding

31

What is the route of administration for warfarin?

Oral

32

Is warfarin plasma bound?

Yes, 97% bound to albumin
This gives warfarin a long half life

33

How is warfarin metabolized?

Liver: hydroxylated in hepatic ER into inactive compound

34

What lab test is used to monitor warfarin therapy?

PT is used to monitor warfarin and its effect on the extrinsic pathway

35

How is INR calculated?

INR is a normalized PT value
INR = PT_patient / PT_normalcontrol

36

What factors effect the dose of oral anticoagulants?

Nutrition, anemia, liver disease, biliary obstruction, drugs

37

What are the main drug-drug mechanisms leading to potentiation of warfarin's effect?

Causing vit K deficiency (ABX)
Displacing warfarin from albumin
Decreasing clotting factor synthesis
Decreasing metabolism
Antiplatelet aggregating properties

38

What are the main drug-drug mechanisms leading to inhibition of warfarin's effect?

Decreasing absorption of warfarin
Increasing metabolism of warfarin

39

What are the main side effects of warfarin?

Bleeding due to hypoprothrombinemia (ecchymoses, purpura, hematuria, hemorrhage)

40

Is warfarin safe to give to pregnant women?

No. Warfarin passes the placental barrier and can cause fetal malformation

41

How does warfarin cause necrosis?

Impaired functionality of protein C due to inhibition of gamma carboxylation of glutamic acid

42

What is the treatment of warfarin overdose?

- Replacement of factors II, VII, IX, X via whole fresh blood infusion or frozen plasma
- Recombinant factor VIIa
- Vitamin K

43

What are the therapeutic uses of vitamin K?

- Antidote for drug-induced hypoprothrombinemia
- Intestinal disorders and surgery
-Hypoprothrombinemias in newborns

44

What are the anti-Xa drugs?

Apixaban
Edoxaban
Rivaroxaban

45

What are the interactions with anti-Xa drugs?

Anti-Xa drugs are potent CYP3A4 inhibitors

46

What is the target of Dabigatran?

Factor IIa (thrombin)

47

Do the new oral anticoagulants require coagulation monitoring?

No.

48

What is a contraindication for dabigatran?

Renal failure
Dabigatran is 100% cleared by the kidney

49

What class of drugs does dabigatran interact with?

Proton pump inhibitors

50

What are the indications for the anti-Xa drugs?

Stroke prevention in AFib patients
Prophylaxis of DVT

51

What is the indication for dabigatran?

Stroke prevention in AFib patients