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PT 1 > L31 Heparin Anticoagulants I > Flashcards

L31 Heparin Anticoagulants I Flashcards

1
Q

What are the three general functions of anticoagulant drugs?

A

To keep blood in a fluid state for the prophylaxis and treatment of thrombosis and for surgical indications

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2
Q

Heparin is a naturally occurring anticoagulant found in ___ along with histamine and serotonin.

A

Granules of mast cells

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3
Q

Heparin is a strongly ___ (basic/acidic) ___ composed of repeating units of sulfated glucuronic acid and sulfated glucosamine.

A

Acidic; mucopolysaccharide

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4
Q

Describe the composition of heparin.

A

It is very heterogenous and is composed of various MW components (low, medium, and high)

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5
Q

What is the source of heparin?

A

Tissue rich in mast cells (beef lung and porcine intestine)

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6
Q

Heparin is dosed in units. 1 mg = ___ units.

A

~180

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7
Q

Discuss the general MOA of heparin.

A
  1. Inhibits the action of activated factor 10a and 2a (thrombin
  2. Inhibits the action of 12a and 11a
  3. Inhibits the aggregation of platelets at high concentrations
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8
Q

Discuss the detailed MOA of heparin.

A

Heparin binds to anti-thrombin III. It induces a conformational change in AT III that exposes a serine protease. This site is able to bind other coagulation proteins and inhibit their activation.

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9
Q

True or false - without AT III, heparin is a weak inhibitor of coagulation.

A

True

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10
Q

Anti-thrombin is a glycoprotein produced by the ___. It is also a serpin - what does this mean?

A

Liver; serine protease inhibitor

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11
Q

Discuss the plasma clearing effect of heparin.

A

Heparin releases lipase and clears turbid plasma of fat chylomicrons

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12
Q

Heparin also binds to vascular lining - what does this do?

A

Neutralizes the positive charge

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13
Q

Heparin also binds to sub-endothelial cells - what does this do?

A

Cause release of tissue factor pathway inhibitor (TFPI)

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14
Q

How is heparin administered?

A

IV and subcutaneous; not oral or rectal

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15
Q

How is the anticoagulant effect of heparin monitored?

A

APTT

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16
Q

What is the therapeutic range of heparin as measured by the APTT?

A

2.0-2.5 times baseline

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17
Q

What is the onset of action and the half life of heparin?

A

Onset of action: 5-10 minutes; half life (IV): ~1 hour depending on the dose

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18
Q

The PK of heparin is ___-dependent.

A

Dose

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19
Q

What are the 4 endogenous modulators of heparin action?

A
  1. Anti-thrombin (main heparin co-factor)
  2. Heparin cofactor II
  3. TFPI
  4. Platelet factor 4 (heparin neutralizing protein)
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20
Q

If you have deficiency of Anti-thrombin, what is the effect of heparin?

A

No effect

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21
Q

What are the two major side effects of heparin?

A
  1. Hemorrhagic complications

2. Heparin induced thrombocytopenia and heparin induced thrombosis

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22
Q

What happens in heparin induced thrombocytopenia?

A

Anti-heparin platelet factor 4 antibodies are generated; these activate platelets and endothelial cells, leading to thrombosis

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23
Q

What are 2 additional side effects of heparin?

A
  1. Osteoporotic manifestations with spontaneous fracture

2. Alopecia

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24
Q

In addition to therapeutic, surgical, and prophylactic anticoagulation, what is one other clinical use of heparin?

A

Unstable angina and related coronary syndromes

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25
Q

What are contraindications for the use of heparin?

A

Patients with HIT or other heparin allergies, active bleeding, hemophilia, thrombocytopenia, recent brain surgery

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26
Q

What is the major heparin antagonist and where is it found?

A

Protamine sulfate; fish sperm

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27
Q

How does protamine sulfate work?

A

Protamine sulfate is strongly basic and combines with strongly acidic heparin to form a stable salt with loss of anticoagulant activity

28
Q

One USP unit of heparin is neutralized by ___ of protamine.

A

10 micrograms

29
Q

IV injection of protamine may cause what effects?

A

Fall in blood pressure and bradycardia

30
Q

Why does low molecular weight heparin involve once daily dosing rather than multiple times?

A

It can penetrate the subcutaneous barrier

31
Q

Discuss the bioavailability of LMW heparins.

A

LMW heparins are bioavailable at 100% (versus 30%)

32
Q

LMW heparins are primarily excreted by the ___.

A

Kidneys

33
Q

What are the clinical advantages of LMW heparins?

A
  1. Better bioavailability
  2. Longer duration of action (4-6 hour half life)
  3. Less bleeding/osteoporosis
  4. Less thrombocytoepnia
34
Q

What are the clinical uses of LMW heparin?

A
  1. Prophylaxis of DVT
  2. Treatment of DVT
  3. Management of acute coronary syndromes
35
Q

What are the clinical disadvantages of LMW heparin?

A
  1. Delayed onset of action
  2. Longer duration of action of LMW makes it difficult to rapidly stop therapy
  3. Prolonged half life in renal failure
  4. Not completely reversed with protamine sulfate
36
Q

Can heparin and LMW heparin be administered during pregnancy?

A

Yes

37
Q

What is antithrombin concentrate used for?

A

To treat patients with acquired or congenital anti-thrombin deficiency; also useful in sepsis and DIC

38
Q

Where does hirudin come from?

A

Leeches

39
Q

What is huridin?

A

Thrombin inhibitor - used in the anti-coagulant management of heparin induced thrombocytopenia

40
Q

What is argatroban?

A

Synthetic anti-thrombin agent used as an anticoagulant in patients who cannot be treated with heparin, also in HIT

41
Q

What is bivalirudin?

A

Synthetic anti-thrombin agent (hybrid between hirudin and tripeptide); approved for PTCA anticoagulation

42
Q

What are the important heparin anticoagulant drugs in this lecture?

A
  1. Unfractionated heparin
  2. LMW heparin
  3. Fondaparinux (pentasaccharide)
  4. Argatroban
  5. Bivalirudin
  6. Hirudin
  7. Anti-thrombin concentration
  8. Protamine sulfate
43
Q

What is the MOA of unfractionated heparin?

A

Complexes with AT and inhibits 10 and 2a; monitored by APTT

44
Q

What is the MOA of LMW heparin?

A

Complexes with AT and inhibits 10 and 2a; monitored by anti-10a

45
Q

What is the MOA of fondaparinux (pentasaccharide)?

A

Complexes with AT and inhibits 10a

46
Q

What is the MOA of argatroban?

A

Directly inhibits 2a

47
Q

How is argatroban excreted? Describe the half life.

A

Liver; short

48
Q

What is the MOA of bivalirudin?

A

Directly inhibits 2a

49
Q

How is bivalirudin excreted? Describe the half life.

A

Renal; short

50
Q

What is the MOA of hirudin?

A

Directly inhibits 2a without a cofactor

51
Q

How is hirudin excreted? Describe the half life.

A

Renal; short

52
Q

What is the MOA of anti-thrombin concentrate?

A

Directly inhibits 2a

53
Q

What is the MOA of protamine sulfate?

A

Heparin antagonist

54
Q

How is unfractionated heparin administered?

A

IV; also subcutaneous

55
Q

How is LMW heparin administered?

A

Subcutaneous (better bioavailability than heparin)

56
Q

How is fondaparinux administered?

A

Subcutaneous

57
Q

How are the other 5 drugs administered?

A

IV

58
Q

What are the indications of unfractionated heparin?

A

Surgical anticoagulation

59
Q

What are the indications of LMW heparin?

A

Prophylaxis and treatment of DVT and ACS

60
Q

What are the indications of fondaparinux?

A

Management of DVT

61
Q

What are the indications of argatroban, bivalirduin, and huridin?

A

Anticoagulation management of HIT patients

62
Q

What are the indications of antithrombin concentrate?

A

DIC, sepsis, thrombophilia, hypercoagulable state

63
Q

What are the indications of protamine sulfate?

A

Antagonist for unfractionated heparin

64
Q

What are the adverse effects for anti-thrombin concentrate?

A

None

65
Q

Heparin is excreted in the ___ and metabolized by the ___ by ___.

A

Urine; liver and RES; heparinase

66
Q

What are the LMW heparins?

A
  1. Dalteparin
  2. Nadroparin
  3. Tinzaparin
  4. Enxoaparin

PT 1 (34 decks)

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