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Basic Haemotology (1204) > Antiplatelet Drugs, Anticoagulants And Fibrinolytics > Flashcards

Antiplatelet Drugs, Anticoagulants And Fibrinolytics Flashcards

1
Q

What is activated partial thromboplastin time (PPT)

A

Laboratory test used to monitor the anticoagulant effect of unfractionated heparin and direct thrombin inhibitors

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2
Q

What is antithrombjn III

A

An endogenous anticlotting protein that irreversibly inactivates thrombin and factor Xa.

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3
Q

What are the names of the glycoproteins on the Platelet surface

A

Glycoprotein 2b/3a

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4
Q

How do glycoproteins primarily aggregate platelets

A

Binding to fibrin

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5
Q

What is the weight of unfractionated heparin

A

5000-30,000

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6
Q

What is the weight of fractionated heparin

A

2000-6000

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7
Q

What is the prothrombin time (PT)

A

Laboratory test used to monitor the anticoagulant effect of warfarin

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8
Q

What is in the Virchows triad

A

Endothelial injury
Abnormal blood flow
Hypercoagulability

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9
Q

What are the three types of anticlotting drugs

A

Anticoagulants
Thrombolytics
Anti platelets

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10
Q

What drugs facilitate clotting

A

Replacement factors, Vitamin K, Antiplasmin drugs

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11
Q

List the drugs associated with anticoagulants

A

Heparin
Direct thrombin inhibitors
Direct factor Xa inhibitors
Warfarin

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12
Q

List the drugs associated with thrombolytics

A

Tissue Plasminogen Activator (tPA derivative)

Streptokinase

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13
Q

List the drugs associated with anti platelets

A

Aspirin
Glycoprotein 2b/3a inhibitors
Adenosine diphosphate inhibitors
Phosphodiestrase (PDE)/ adenosine reuptake inhibitors

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14
Q

What pathway does
I heparin
II warfarin
target

A

Intrinsic

Extrinsic

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15
Q

What is the MOA of
I Heparin
II Warfarin

A

Inactivates thrombin and factor Xa

Inhibits Synthesis if clotting Factors

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16
Q

What is the route of administration for
I Heparin
II Warfarin

A

IV or SubQ

PO

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17
Q

True or false Heparin crosses the placenta or into breast milk but Warfarin doesn’t

A

False, Warfarin crosses the placenta (teratogenic) but Heparin doesn’t

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18
Q

How long is the offset of
I Heparin
II Warfarin

A

Rapid (minutes)

Slow (hours)

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19
Q

How long is the duration of
I Heparin
II Warfarin

A

Brief (hours)

Prolonged (days)

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20
Q

True or false Heparin has lesser drug interactions than Warfarin which has many

A

True

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21
Q

How is
I Heparin
II Warfarin

Eliminated

A

Renally

Hepatically

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22
Q

What is used to monitor
I Heparin
II Warfarin

A

PTT

PT

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23
Q

What is the antidote for
I Heparin
II Warfarin

A

Protamine

Phytomenadione (Vitamin K)

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24
Q

What are the low molecular weight anitthrombin III activators

A

Enoxaparin

Dalteparin

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25
Q

What are the Vitamin K antagonists

A

Warfarin

Phenprocoumon (Acenocoumarol)

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26
Q

What are the drugs associated with being thrombin inhibitors

A 
Hirudin 
Argatroban
Bivalirudin
Davila Tran
Desirudin
Lepirudin
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27
Q

What are the drugs associated with being Heparin and LMWH

A 
Heparin
Ardeparin
Dalteparin
Danaparoid
Exoxaparin
Tinzaparin
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28
Q

What are the drugs associated with being Direct Factor Xa inhibitors

A

Apixaban
Edoxaban
Rivaroxaban

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29
Q

What is the source of injectable heparin and LMWH

A

Procine intestinal mucosa

Bovine lung

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30
Q

Heparin and LMWH is associated with the family of _______ ________

A

Sulphated glycosaminoglycan

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31
Q

What is the molecular weight range of injectable heparin

A

5000-40000 daltons

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32
Q

What is the molecular weight of LMWH

A

1000-10,000 daltons using gel filtration chromatography

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33
Q

What is the MOA of Heparin

A

Cofactor of Antithrombin III
Increases the rate of ANTIII reaction by 1000
Also increase in activation of IX, Xa, XIa, XIIa and protein C and S
1:10 binding ration with all factors

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34
Q

What is the MOA of LMWH

A

Have only one binding site for ANTI- III

Therefore increase inactivation of IX, Xa, XIa and XIIa

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35
Q

True or false, only the LMWH is active in the invivo and in vitro method

A

False both Heparin and LMWH

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36
Q

True or false , LMWH doesn’t inactivate IIa

A

True

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37
Q

True or false, only long chains of Heparin can inhibit the action of factor Xa by binding to antithrombin (AT)

A

False, any size heparin chain can inhibit the factor Xa

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38
Q

True or false, in order to inactivate thrombin (IIa), the heparin molecule must be long enough to bind to both antithrombin and thrombin

A

True, it must be long in order to bind to both antithrombin and thrombin

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39
Q

What type of Heparin would you use to inactive thrombin

A

Unfractionated Heparin

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40
Q

LMWH binds only to ______ and therefor increases inactivation of Factors __________

A

Antithrombin III and IXa, Xa, XIa and XIIa

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41
Q

Why is LMWH, more prescribed than Heparin

A

Less monitoring
More predictable anticoagulant response
Same efficacy as heparin

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42
Q

True or false, Heparin is polar

A

True

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43
Q

What is the :
I. Way of Administrating
II. Onset

Of heparin

A

IV and subcutaneous,

Fast, 60 minutes

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44
Q

What is the bioavailability of Heparin after SC

A

20%

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45
Q

Why is the initial loading dose required

A

5000 U

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46
Q

Explain the reason as to why Heparin is unpredictable

A

Non-specific binding to plasma proteins, endothelial cells, Macrophages
vWF- need to saturate

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47
Q

What is the half life of Heparin

A

40-90 minutes

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48
Q

The aPPT for monitoring Heparin should not be

A

> 2.5 X normal

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49
Q

True or false, the Ti for Heparin is low

A

True

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50
Q

How is Heparin eliminated

A

Internalized and destroyed by Reticulocyte-endothelial system, heparinase enzyme

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51
Q

What are the advantages of LMWH vs UH

A

Less inhibition of platelet function Lower incidence of Thrombocytopenia and Thrombosis (HIT Syndrome)

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52
Q

How does the use of LMWH Lower the risk of thrombocytopenia or HIT

A

Less interaction with platelet factor 4

Fewer heparin- dependent lgG antibodies

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53
Q

What are the adverse drug reactions of Heparin

A

Inhibits aldosterone- hyperkalemia= HIT potential
Causes necrosis due to Protein C
Anticoagulant
Initial transient reduction in platelet count

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54
Q

Thrombocytopenia usually occurs 2-14 days after the start of therapy
____% patients receiving heparin
____% patients receiving LMWH

A

5%

1%

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55
Q

HIT Incidence rates for
Thrombosis
Amputations
Death

A

30-50%
20%
30%

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56
Q

What is used during Heparin Overdose

A

Protamine sulphate

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57
Q

How is Protamine sulphate given

A

Slow IV

Given at 1Mg/ 100 U of heparin remaining

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58
Q

Protamine sulphate is given routinely after________ surgery to reverse effects of Heparin

A

Cardiac

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59
Q

What is the adverse effects of Protamine Sulphate

A

Histamine release

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60
Q

True or false, Heparin and LMWH are both given at 5000 U

A

True

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61
Q

What is the bioavailability of LMWH after SC

A

90%

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62
Q

What is the half life of LMWH

A

T times longer than heparin

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63
Q

Why is there no monitoring required for LMWH

A

There is no change in aPTT

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64
Q

True or false, Heparin is more expensive than LMWH

A

False LMWH is more expensive

65
Q

What is the difference between the Thrombin inhibitor drugs and heparin drugs

A

Heparin drugs require the binding of Antithrombin III in order to inhibit the binding of Thrombin

66
Q

What are the names of the Thrombin inhibitor drugs that are taken via IV

A

Hirudin

Lepuridin

67
Q

What is the name of the Thrombin inhibitor that is taken orally

A

Dinihatran etexilate

68
Q

True or false , Thrombin inhibitors are approved for treatment of anticoagulant when there is or the potential for HIT

A

True

69
Q

How is hirudin produced

A

Synthesized via recombinant DNA technology

70
Q

How is Hirudin eliminated

A

Hepatic metabolism

71
Q

What is the half life of hirudin

A

2 and a third hours

72
Q

What are the adverse effects of Hirudin

A

Liver injury, Renal insufficiency

73
Q

True or false, Heparin blocks the activation of Clotting factors while Warfarin speeds up the inactivation of The clotting Factors

A

False, it is the other way around

74
Q

What is the oral coagulant for warfarin

A

Coumarin

75
Q

Where is Coumarin prepared from

A

Clover leaves

76
Q

What is the MOA of Warfarin

A

Competively inhibits the Vitamin K epoxide reductase complex 1 (-VPORC1), which is essential for activating the Vitamin K available in the body
Through this method, Warfarin can deplete functional Vitamin K reserves and therefore reduce synthesis of active clotting Factors

77
Q 
What is the half life for Warfarin in  cofactors (hrs)
VII
IX
X
II
Protein C
Protein S
A 
6
24
36
60
8
30
78
Q

Where is Warfarin eliminated and by what enzyme

A

Liver CYTP450

79
Q

Is Warfarin polar or non polar

A

Non polar

80
Q

What is the onset of Warfarin

A

Slow - 48 hours

81
Q

What is the duration of Warfarin

A

4-5 days

82
Q

What is the half life range of Warfarin

A

25-60 hours

83
Q

True or false, Warfarin is well absorbed

A

True pK 2-8 hours

84
Q

What Aretha ADR/ toxic effects of Warfarin

A

Diarrhea
Overdose - bleeding
Skin necrosis
Drug interactions

85
Q

What is used to treat Warfarin

A

Vitamin K

86
Q

True or false, Warfarin has a low TI

A

True

87
Q

What is the therapeutic range of warfarin

A

2-3

88
Q

What is the

i. onset of plasma in the reversal of warfarin
ii. duration

A

Rapid but short lasting

89
Q

What is the onset of Vitamin K in the reversal of of warfarin
ii. duration

A

Vitamin K- not rapid but lasts 1-2 weeks

90
Q

True or false, It is advised to use vitamin k if you are planning on restarting warfarin within next week

A

false

91
Q

Warfarin Induced Skin Necrosis usually occurs in what range after initiation

A

3-6 days

92
Q

True or false, Warfarin induced skin necrosis is common

A

False it is rare

93
Q

What persons are most likely to be affected by Warfarin Induced skin necrosis

A

Obese women

Postmenopausal women

94
Q

What is the treatment for Warfarin induced skin necrosis

A

Heparin

95
Q

Which drug inhibits liver enzymes

A

Cimetidine

96
Q

Cimetidine ______ clearance of Warfarin

A

Decreases

97
Q

What drugs increase the clearance of Warfarin

A

Barbiturates, rifampin, phenytoin

98
Q

Which drugs induces liver enzymes

A

Barbiturates, rifampin, phenytoin

99
Q

How does Disulfiram affect interactions with Warfarin

A

Causes Displacement from plasma proteins, thereby increasing free warfarin

100
Q

How does Broad Spectrum Antibiotics affect drug interaction with Warfarin

A

Decrease absorption of Vitamin K, decreases clotting factors

Increases Warfarin activity

101
Q

What type of Anti-clotting drug decreases the formation of chemical signals that promote platelet aggregation

A

Antiplatelet drugs

102
Q

Anti platelet drugs are mainly administer for what specific cases

A

Specific Prophylaxis of arterial thrombosis

During management of heart attacks

103
Q

What are the different types of antiplatelet drugs

A

COX/TXA2 inhibitor
IIB/IIIA receptor antagonists
P2Y12 ADP receptor blockers
Phosphodiesterase Inhibitor

104
Q

What are the different P2Y12 ADP receptor blockers

A

Ticlopidine
Clopidogrel
Prasugrel
Ticagrelor

105
Q

What are the different IIB/IIIA receptor antagonists

A

Abciximab
Eptifibatide
Tirofiban

106
Q

What are the different phosphodiesterase inhibitors

A

Dipyridamole

107
Q

What is the name of a COX/TXA2 inhibitor

A

Aspirin

108
Q

TXA2 is a potent inducer of platelets _________

A

Aggregation

109
Q

Aspirin acetylates ________ inhibiting platelet aggregation for a range of _________ days

A

Cyclooxygenase-1 (COX-1)

5 or 7 days

110
Q

What is the MOA of aspirin

A

irreversible inhibition of COX 1

In platelets prevents formation of TX A2 which prevents platelet aggregation

111
Q

What is the oral Dose of Aspirin

A

160-320mg/d

112
Q

What is the onset of Aspirin

A

30-60 mins

113
Q

Where is Aspirin eliminated

A

Liver

114
Q

What is the duration of Aspirin

A

7-9 days

115
Q

What is the adverse reaction of Aspirin

A

GIT irritation

116
Q

What is the MOA of Dipyridamole

A

Inhibits phosphodiesterase = cAMP
cAMP competes with ADP for binding site = blocking response to ADP
High amounts of AMP decreases Ca2+ concentration, therefor decreasing aggregation of platelets

117
Q

What is Dipyridamole usually used with

A

Aspirin or Warfarin

118
Q

In ______ doses, Dipyridamole can be used as a vasodilator

A

High

119
Q

Dipyridamole has a _____ efficacy

A

low

120
Q

What is Dipyridamole used for

A

Prophylactic use

121
Q

How is Dipyridamole excreted

A

Liver metabolizes and then is excreted by bile

122
Q

True or False, Dipyridamole is well absorbed

A

True

123
Q

What is the adverse effects of Dipyridamole

A

Headaches, Dizziness

Overdoses= hypotension

124
Q

True or false, Dipyridamole has a high PPB

A

True

125
Q

What is the PK of Dipyridamole

A

75 minutes

126
Q

What are the ADP receptor antagonists

A

Ticlopidine (Ticlid)
Prasugrel
Clopidogrel (Plavix)
Ticagrelor

127
Q

True or False, Dipryidamole doesn’t affect bleeding time

A

True

128
Q

True or False, ADP receptor antagonists don’t affect bleeding time

A

False, they do

129
Q

Dipyridamole inhibits the reuptake of _______

A

Adenosine

130
Q

ADP receptor antagonists work by inactivating the platelet _______ by irreversibly binding to the receptor, thus having a prolonged action

A

P2Y12 (ADP)

131
Q

ADP receptor antagonists work by inhibiting the binding of _______ (factorI) to activated platelet

A

Fibrinogen

132
Q

What is the route of administration for Clopidogrel

A

Oral

133
Q

What is the PK of Clopidrogrel

A

2 hours

134
Q

What is the Pro-drug activated by

A

CYP450 (2C19)

135
Q

What is the onset of Clopidrogel

A

4-8 days

136
Q

What is the duration of Clopidrogel

A

14 days

137
Q

What is ADR of Clopidrogrel

A

Diarrhea, bleeding

138
Q

What is the MOA of GPIIb/IIIa receptor antagonist

A

Blocks the binding of fibrinogen and Von Wilebrand Factor to the glycoprotein IIb/IIIa on the surface of the platelet.

139
Q

What is the monoclonal antibody to the Glycoprotein IIIa/IIb

A

Abcixmab

140
Q

What are the platelet IIb/IIIa antagonists

A

Eptifibatide, Tirofiban

141
Q

GPIIb/IIIa antagonists increase the risk of bleeding, particularly at the site of _______

A

Arterial access

142
Q

True or false, Abcixmab irreversibly binds to the GPIIb/IIIa

A

True

143
Q

Abcixmab is used with _______

A

Aspirin and Heparin

144
Q

What is the route of administration for Abcixmab

A

IV fusion

145
Q

What is the onset of Abcixmab

A

rapid

146
Q

What is the half life of Abcixmab

A

10 minutes

147
Q

What is the duration of Abcixmab

A

48 hours

148
Q

What are the adverse effects of Abcixmab

A

Fever headaches, thrombocytopenia

149
Q

Where is Abcixmab metabolized

A

Liver

150
Q

What are the Thrombolytic Drugs

A

Streptokinase

151
Q

What drugs are used to lyse already formed clots

A

Thrombolytic drugs

152
Q

What are two tissue- plasminogen activators

A

Reteplase, Tenecteplase
(more expensive)
(Only used in emergency setting )

153
Q

What is the MOA of Fibrinolytic drugs

A

Increase the conversion of plasminogen to plasmin

only used in emergency setting

154
Q

What is streptokinase dependent on

A

Plasminogen Availability

155
Q

What is streptokinase given with

A

Hydrocortisone IV

156
Q

What is the half life of streptokinase

A

40-80 hours

157
Q

What is the duration of streptokinase

A

12 hours

158
Q

What is the adverse effects of Fibrinolytics

A

Antibody formation

159
Q

Where are Fibrinolytics metabolized

A

Liver

Basic Haemotology (1204) (16 decks)

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