Anticoagulants, Antiplatelets, and Thrombolytics- leblanc Flashcards Preview

Block 7 Week 4 > Anticoagulants, Antiplatelets, and Thrombolytics- leblanc > Flashcards

Flashcards in Anticoagulants, Antiplatelets, and Thrombolytics- leblanc Deck (146)
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1

What are some anticoagulants?

-Unfractionated or high molecular weight heparin
-low molecular weight heparins
-factor IIa and Xa inhibitors
-Warfarin (coumadin)

2

What is a procoagulant?

desmopressin acetate

3

What are some antiplatelet drugs?

Acetylsalicylic acid (aspirin)
Clopidogrel bisulfate (Plavix)
Abciximab (ReoPro)

4

What are some thrombolytic agents?

Tissue plasminogen activator (t-PA)

5

What are some antagonists?

Protamine sulfate
Aminocaproic acid

6

T or F
under normal physiological conditions, little or no intravascular coagulation occurs

T

7

Why don't you have intravascular coagulation under normal physiological conditions?

-Dilution
-Presence of plasma inhibitors
-activated clotting factors are rapidly removed by the liver

8

When vascular damage occurs, several physiologic reactions participate to contrl blood loss?

Platelet adhesion reaction
Platelet activation
Platelet aggregation
Formation of a clot (coagulatio)
Fibrinolysis

9

What are the three major risk factors for thromboembolism?

-abnormalities of blood flow
-abnormalities of surfaces in contact with blood
-abnormalities of clotting components

10

How do you get vasoconstriction or vasospasm in hemostasis?

thomboxane A2 (TA2) and serotonin (5-HT) released by platelets which triggers powerful constrictions stimulating the contraction of smooth muscle cells within the walls of blood vessels

11

What is this:
coagulation occurs due to trauma originating from the extra-vascular space (formation of a macromolecular complex involving thromboplastin or tissue factor, and factor VII); the most important in vivo.

Extrinsic Pathway

12

What is this:
coagulation is triggered by trauma to the blood itself (from large glycoprotein complexes released by platelets)

Intrinisic pathway

13

What does t-PA and urokinase do?

upregulated plasmin to degrade blood clots (degrades fibrin, fibrinogen)

14

So tell me what happens if you have a damaged vessel wall?

platelet adhesion and initiation of coagulation

15

If you get platelet adhesion and thrombin what happens next?

you get release of mediators which will cause platelet aggregtes and fibrin

16

What will platelet aggregates and fibrin cause?

a thrombus

17

What will a thrombus induce?

fibrinolysis which will degrade products

18

What three major categories of anticoagulant drugs?

Direct acting anticoagulants
Indirect acting anticoagulants
Antiplatelet agents

19

What are some examples of direct acting anticoagulants?

Calcium Chelators (useful for in vitro testing; sodium citrate, EDTA)
Heparin (unfractionated and low molecular weight fractions)
Factor IIa and Xa inhibitors

20

What is an example of an indirect acting anticoagulants?

warfarin (coumadin)

21

What is an example of an antiplatelet agent?

aspirin, plavix

22

What are the clinical tests for assessing antiplatelet, anticoagulant and thrombolytic therapies?

Bleeding time
platelet count (normal: 150,000-400,000)
Pro-thrombin time (PT)

23

What does pro-thrombin time tell you?

reflects alterations in the extrinsic pathway

24

What is a normal pro-thrombin time?

12 seconds

25

What does INR stand for and what does it tell you?

International normalized ratio
-> used to normalize PT

26

What is the desired therapeutic INR?

2 and 3 (human thromboplastin)

27

(blank) is an enzyme released from damaged cells, especially platelets, that converts prothrombin to thrombin during the early stages of blood coagulation

thromboplastin

28

What test will reflect the intrinsic pathway?

aPTT (activated partial thromboplastin time)

29

What is the normal aPTT?

24 to 34 seconds

30

How do you test for abnormalities in fibrinogen?

immunological tests

31

What test will detect simple deficiencies of a factor or the presence of a clotting inhibitor?

Mixing studies

32

(blank) is an anionic mixture of linear mucopolysaccharide molecules with molecular weights in the range of 3,000 to 30,000

Heparin

33

(blank) is prepared from bovine lung and porcine intestinal mucosa

Commercial heparin

34

What does heparin do?

inhibits blood coagulation by forming complexes with an a2 globin and each of the activated proteases of the coagulation cascade.

35

After formation of the heparin-antithrombin III-coagulation factor, what happens to heparin?

it is released and becomes available again to bind to gree ATIII

36

What does heparin bind to and upregulate and why?

antithrombin III to form a complex that will inhibit Kallikrein, XIIa, XIa, IXa, Xa, thrombin)

37

Heparin blocks conversion of (blank) to (blank) and thus inhibits the synthesis of fibrin from fibrinogen

prothrombin to thrombin

38

What factors does heparin inhibit?

factors Xa and thrombin (IIa) and factors IXa and XIa

39

At low doses heparin primarily neutralizes factor (blank). At high doses, it prevents the thrombin-induced activation of platelets, and activation factors (bank) and (blank)

XA
V and VIII

40

What inhibits platelet function and increases vascular permeability?

Heparin

41

What factors are vit K dependent?

2,7,9,10 and proteins C and S

42

What is super scary about heparin?

some people have a fucked up reaction to it called HIT which induces a hypercoagulable state! (heparin induced thrombocytopenia)

43

What is HIT?

You get IgG antibodies to heparin when it is bound to platelet factor 4 inducing a hypercoagauable state

44

T or F
Heparin is not effective after oral administration

T

45

How should you give heparin?

intravenous infusion or deep sub-cutaneous injections (may take 2-4 hours to reach therapeutic plasma levels)

46

Why shouldnt you give heparin via intramuscular injections?

due to the formation of hematomas

47

What happens if you give heparin to a pregnant mother or one who is breastfeeding?

nothing cuz heparin does not cross the placenta and does not pass into maternal milk

48

Heparin is (blank) dependent

dose-> half life depends on the dose administered

49

What is the half life of heparin at 100?
400?
800?

1 hour
2.5 hours
5 hours

50

When should you not give heparin?

any situation where active bleeding must be avoided (ulcerative lesions, intracranial hemorrhage, brain or spinal cord surgery)
-Patients with thrombocytopenia, or prior history of HIT
-patients susceptible to severe allergies; heparin is extracted from animal sources
-severe hypertension
-older patients (especially women)

51

What do you give a patient if they are overdosing on heparin?

-simple withdrawal
-protamine sulfate (PS): highly basic peptide that binds heparin and thus neutralizes its effect

52

What is the dosage of protamine sulfate (PS)?

1 mg of PS for every 100 units of heparin (not to exceed 50 mg for any 10 min period)

53

What testing should you give following heparin treatment

-aPTTT 1.5 to 2.5 times normal
(normal ~24-34 seconds)
-antifactor Xa heparin activity assay (0.3-0.7 units/ml)
-hematocrit (Hct)
-platelet count

54

How often should you give antifactor Xa heparin activity assay?

6 hour intervals after initiation of heparin infusion until stabilization, then once daily

55

What are the four low molecular weight forms of heparin (LMWH)?

Dalteparin sodium (fragmin)
Tinzaparin Sodium (innohep)
Enoxaparin (lovenox)
Fondaparinux (arixtra)

56

LMWH selectively accelerates interactions of antithrombin with (blank)

factor Xa

57

Unfractionated heparin accelerates interaction of antithrombin with (blank) and (blank)

thrombin
Factor Xa

58

Both LMWH and UFH have equal efficacy.
T or F

T

59

Which has a more predictable outcome and a longer half-life than the other (2x the half-life); UFH or LMWH?

LMWH

60

Which is better LMWH or UFH?

LMWH because it has less frequent bleeding and you can dose it less frequently AND has increased bioavailability from site of injection.
(LMWH 90%, UFH 20%)

61

What are the clinical indications for UFH or LMWH therapy?

-blood transfusions
-atrial fibrillation
-disseminated intravascular coagulation (DIC)
-open heart surgery
-pulmonary embolism
-venous thromboembolism
-venous catheter occlusion

62

What factor is thrombin?

IIa

63

What is this:
a recombinant 65-AA polypeptide derivative of hirudin, the natural anticoagulant isolated from the salivary gland of medicinal leech.

Lepirudin (refludan)-> a thrombin inhibitor

64

How do thrombin inhibitors work?

block the enzyme by binding to the catalytic site

65

What is this:
a synthetic 20 amino acid polypeptide inhibitor with similar activity to lepirudin

Bivalirudin (angiomax)-> a thrombin inhibitor

66

What is this: synthetic compound based on the structure of L-arginine

Argatroban-> a thrombin inhibitor

67

How do you give the thrombin inhibitors (argatroban, bivalirudin, lepirudin)?

IV infusion

68

What are the clinical indications for thrombin inhibitors?

Patients susceptible to developing HIT
Coronary angioplasty or coronary bypass surgery

69

What is the first orally active factor IIa inhibitor approved by the FDA?

Dabigatran Etexilate (pradaxa/ pradax)

70

What is the drug company name for lepirudin?

refludan

71

What is the drug company name for bivalirudin?

angiomax

72

What are the clinical indications for Pradaxa/pradax?

-thromboembolic disorders
-prophylactic anticoagulant used to minimize the risk of stroke in pnts with non-valvular a fib.

73

What are the Factor Xa inhibitors?

Rivaroxaban (Xarelto)
Apixaban (Eliquis)

74

What is Rivaroxaban (Xarelto)?

an oral anticoagulant that is a factor Xa inhibitor.

75

What are the clinical indications for Rivaroxaban (xarelto)?

DVT: treatment and secondary prophylaxis
Hip or knee surgery as prophylactic agent
Non-vascular A Fib
cerebrovascular accident
PE

76

What are the clinical indications for Apixaban (eliquis)?

Non-valvular A fib.
CV accidents

77

What is the most common oral anticoagulant?

Warfarin (coumadin)

78

When does coumadin (warfarin) start to work?

only works in vivo after a latent period of 12 to 24 hours

79

How does coumadin (warfarin) work?

it is a structural analogue of vit K and depletes vit K so that the vit K dependent clotting factors cant work

80

Warfarin is a racemic mixture of two (blank)

enantiomers (R and S forms)

81

What are the vit k dependent clotting factors that warfarin inhibits?

VII, IX, X and prothrombin (II)

82

What does Vit K do for certain clotting factors?

Post-ribosomal carboxylation of specific glutamic acid residues. These AA residues chelates Ca2+

83

Warfarin down-regulates (blank)

protein C

84

What does protein c do?

when bound to thrombomodulin in endothelial cells, alters the specificity of thrombin and favors the degredation of factors Va and VIIIa into inactive proteases.

85

What is this:
These proteins are naturally occuring anticoagulants

Protein C and Protein S

86

What explains the procoagulant activity of warfarin observed in the early stage of therapy?

well warfarin down regulates protein C which is an natural anticoagulant therefore you get some coagulation :(

87

What is the half-life of factor VII?

6 hours

88

What is the half life of Factor IX?

24 hours

89

What is the half life of factor X?

40 hours

90

What is the half life of prothrombin?

60 hours

91

Warfarin is largely bound to (blank) and is metablized by the (Blank) into inactive metabolites which are then excreted into the urine

albumin (>98%)
liver by cytochrome p450

92

How do you monitor warfarin?

with PT (prothrombin time) and INR

93

How do you treat warfarin overdose?

-withdrawal of drug
-give vit K (24 hour delay) supplementation
-transfusion of whole blood or plasma (major bleeding)

94

What are the contraindications for warfarin?

Conditions where active bleeding must be avoided, Vitamin K deficiency and severe hepatic or renal disease, where intensive salicylate therapy is required, and in pregnant women

95

Why can you not give warfarin to pregnant women or breast feeding women?

Coumadin anticoagulants pass the placental barrier and may lead to abortion and birth defects
AND
Newborn infants are have low vit K so they are more susceptible to oral anticoags and have lower rates of metabolisms

96

What will diminish the response to warfarin?

-inhibition of drug absorption
-induction of hepatic microsomal enzymes
-stimulation of the synthesis of clotting factors

97

What will increase the response to warfarin?

-displacement of anticoagulant from plasma proteins
-inhibition of hepatic microsomal enzymes
-reduction in availability of vit K
-inhibition of synthesis of clotting factors
-decreased platelet aggregation (e.g. aspirin)

98

What is a drug that inhibits drug absorption?

cholestyramine

99

(blank) is a synthetic analogue of the pituitary antiduiretic hormone (ADH)

desmopressin acetate

100

What does desmopressin acetate do?

stimulates the activity of coag factor VIII (8)

101

What do you use desmopressin for?

hemophilia A with factor 8 levels equal or greater than 5% OR in clients who have factor 8 antibodies.
In treatment of classic von willebrands disease (type I) and when abnormal molecular form of factor 8 antigen is present

102

What does acetylsalicicylic acid do?

inhibits release of ADP by platelets and their aggregation

103

What is the MOA of acetylsalicycic acid (aspirin)?

acetylates the COX enzyme of platelets so that it can no longer create thromboxane which induces platelet aggregation and vasoconstriction

104

A (blank) dose (160-320 mg) may be more effective at inhibiting thromboxane A2 than PGI2

low dose

105

THe effect of aspirin is (blank)

irreversibe

106

Why is aspirin used in CV stuff?

not known to prevent primary MI but known to be beneficial in patients with history of vascular events (secondary)

107

(blank) represents an alternative antiplatelet drug for treatment of recurrent stroke in patients intolerant to aspirin

Ticlopidine (Ticlid)

108

What is the MOA of ticlopidine (ticlid)?

Inhibits response of ADP on its platelet receptor and thus prevents aggregation of platelets - > impairs GPIIb/IIIa receptor

109

How does clopidogrel bisulfate (plavix) work?

same was as triclopidine, impairs GPIIb/IIIa receptor thus inhibits platelet aggregation

110

Why is clipidogrel bisulfate (plavex) better than ticlid?

has less side effects

111

What is this:
chimeric monoclonal antibody inhibitor of platelet glycoprotein IIb/IIIaa

Abciximab (reopro)

112

What does abciximab prevent?

prevents binding of fibrinogen and von willebrand factor and prevents platelet aggregation.

113

What is the primary use of abciximab (reopro)?

acute coronary syndromes and percutaneous coronary intervention

114

The fibrinoytic system dissolves intravascular clots as a result of the action of (blank)

Plasmin

115

What does plasmin do?

digests fibrin

116

How do you get plasminogen to become plasmin?

via cleavage of peptide bond

117

(blank) is a relatively non-specific protease, which digests fibrin clots and other plasma proteins, including several coagulation factors.

Plasmin

118

Therapy with (blank) drugs tend to dissolve pathological thrombi and also fibrin deposits at sites of vascular injury.

Thrombolytic drugs

119

What is a worry about using thrombolytic agents?

hemorrhage as a major side effect

120

Thrombolytic therapy is indicated in patients with extensive (blank), (blank) and (blank)

pulmonary emboli
severe iliofemoral thrombophlebitis and acute coronary occlusion

121

(blank) is released from endothelial cells in response to various signals, including stasis produced by vascular occlusion.

tissue plasminogen activator (t-PA)

122

(blank) binds to fibrin and converts plasminogen to plasmin

t-PA (tissue plasminogen activator)

123

Free plasmin is rapidly inhibited in the plasma by an a2-antiplasmin. (blank-bound) plasmin is protected from inhibition

fibrin

124

t-PA (activase) is a (blank) protease

serine

125

T-PA (activase) is a (good/poor) plasminogen activator in the absence of fibrin

Poor

126

t-PA binds to (blank) and activates bound plasminogen several hundred-fold more rapidly than it activates Plasminogen in the circulation.

fibrin

127

(blank) is a protein produced by beta-hemolytic streptococci

streptokinase

128

How does streptokinase (streptase) work?

forms non-covalent complex with plasminogen -> induces conformational change that exposes active site on plasminogen that cleaves a peptide bond on free plasminogen molecules to form free plasmin

129

Does streptokinase (streptase) have intrinisc enzymatic activity?

no

130

What are the 2 thrombolytic agents?

Tissue plasminogen activator (t-PA, Activase)
Streptokinase (streptase)

131

You should NOT give thrombolytic therapy to someone who has had surgery within the last (blank) days. What kinds of surgeries does this include?

10
organ biopsy, puncture of non-compressible vessles, serious trauma, cardiopulmonary resuscitation

132

You should NOT give thrombolytic therapy to someone who has serious (Blank) bleeding within the last 3 months

GI

133

You should NOT give thrombolytic agents to anyone with a history of (blank)

hypertension-> diastolic pressure greater than 110 mm Hg

134

You should not give thrombolytic agents to anyone with active bleeding or hemorrhagic disorders and patients with previous (blnak) or (blank)

cerebrovascular accident
active intracranial bleeding

135

(blank) prevents the binding of plasminogen and plasmin to fibrin. So what does it do?

Aminocaproic acid
inhibits fibrinolysis

136

When do you use aminocaproic acid?

can reverse states that are associated with excessive fibrinolysis

137

What signs and symptoms demonstrated by D.P. are consistent with DVT?

-unilateral leg swelling accompanied by local tenderness and pain
-discoloration of the affected limb
-arterial spasm, cyanosis from obstruction or reddish color from perivascuar inflammation

138

How do you test for DVT?

-l-fibrinogen scanning
-D-dimer test (detects fibrin breakdown product D-dimer)
-Impedance plethysmography (pneumatic cuffs for detection of blood volume changes)
-doppler ultrasonography

139

What is the standardized dosing regimen for heparin?

5,000 U IV to be followed by a continuous infusion of 1,000 U/hr

140

What is the loading dose for heparin?

70-100 U/kg

141

What is the maintenance dose for heparin?

15-25 U/kg/hr

142

When can you give a aPTT?

6 hours after loading dose

143

What is the correct dose for therapeutic heparin level?

1.5-2.5 times that of normal range (24 to 34 sec is normal)

144

How do you monitor heparin

check aPTT every 6 hours after loading dose, and 6 hours after any change in infusion rate
-> if dosing is stable, aPTT should be evauated once daily, along with Hct and platelet count (1 to 2 days)

145

How long should heparin therapy be maintained?

traditionally 7-10 days
Warfarin initiated around day 5 (3 to 6 months)

146

Which drug has the latent period, heparin or warfarin?

warfarin!!!