Test 1: Wk1: 5 Coagulation and Anticoagulants - Valentovic Flashcards
(130 cards)
1
Q
Anticoagulants (6)
A
Heparin LMW Heparin Warfarin Argatroban Dabagatran XaInhibitors
2
Q
Anticoagulants work by
A
inhibiting fibrin formation
3
Q
Antiplatelets (5)
A
Aspirin, Dipyridamole, Clopidogrel, Abciximab & Eptifibatide
4
Q
Antiplatelets work by
A
inhibit platelet aggregation
5
Q
Thrombolytics/ Fibrinolytics (4)
A
Streptokinase, Alteplase, Anistreplase& Tenecteplase
6
Q
Thrombolytics/ Fibrinolytics work by
A
dissolve formed fibrin clots
7
Q
Heparin Natural Product
A
Porcine MW 5-30 kDa
8
Q
Heparin accelerates the reaction of — with —
A
AT-III (antithrombin 3) with coagulation factors
9
Q
Heparin — binds AT-III and induces —
A
irreversibly
conformational change
10
Q
Heparin binds AT-III — times faster with what coagulation factors
A
1000x
II, X, XI and XII
11
Q
Heparin - active coagulation factors bind — to AT-III at the — site. This prevents — generation
A
irreversibly
Arg-Ser
Fibrin
12
Q
AT-III is a — substrate
A
suicide; it binds and doesnt let go
13
Q
Heparin is an anticoagulant in
A
vitro
14
Q
Heparin use in vivo
A
Tx of Venous Thrombosis
Tx of Pulmonary thromboembolism
15
Q
Is Heparin approved in pregnant women
A
yes - it does not cross placenta
16
Q
Heparin Administration
What administration is contraindicated
A
SC or IV
IM contraindicated - induce hematoma
17
Q
how is Heparin montored
A
aPTT
18
Q
How much does heparin increase aPTT
A
1.5 - 2.5 x
19
Q
Heparin has a lipid clearing effect that
A
increase lipoprotein lipase activity
20
Q
What does aPTT asses
A
intrinsic pathway and factors I, II and X
21
Q
Heparin Adverse Effects
A
- bleeding
- Thrombocytopenia Type 1 and 2
22
Q
Thrombocytopenia Type I
A
non-immune medicated platelet heparin interaction
23
Q
Thrombocytopenia Type II
A
immune mediated; begins 4-10 days after tx
ab form to heparin-platelet factor 4 complex which binds to platelet surface causing aggregation
24
Q
What should be monitored in long term use of unfractionated heparin
A
platelet count
25
Reverse Heparin with
Protamine
| plasma or whole blood
26
Protamine MOA
binds heparin disabling anticoagulant activity
27
Protamine Allergy
diabetics
| Fish allergy
28
Heparin Contrindications
Bleeding disorder
| pre-existing bleeding site
29
low molecular weight Heparin (3)
Enoxaparin
Dalteparin
Tinzaparin
30
low molecular weight Heparin weight
4500 daltons
31
low molecular weight Heparin is too small to do what
simultaneously bind ATIII and thrombin
32
low molecular weight Heparin MOA
enhance ATIII inactivation of factor Xa
low affinity for thrombin
33
low molecular weight Heparin uses (4)
prophylaxis
acute venous thrombosis
DVT
Unstable angina or non Q-wave MI
34
low molecular weight Heparin administration
SC 1/day
35
low molecular weight Heparin monitoring
anti Xa activity
36
is low molecular weight Heparin approved in pregnant women
yes
37
LMW Enoxaparin vs Heparin
longer half life
outptx
lower thrombocytopenia
Predictable
38
Fondaparinux is a
Synthetic Pentasaccharide
39
Fondaparinux MOA
Specific for ATIII inactivation of Factor Xa
40
Fondaparinux adminstration
IV, SC
41
Fondaparinux uses
Prophylaxis and acute deep vein thrombosis
42
can Fondaparinux be used in pregnant women
yes
43
Fondaparinux contraindications
Contraindicated in bleeding or severe renal impairment
44
Warfarin is an anticoagulant where
only in vivo
Warfarin does not inhibit clotting when directly added to blood
45
Warfarin MOA
inhibits synthesis of biologically active VitK dependent clotting factors
46
Warfarin inhibits what enzyme
Vit K epoxide reductase
Vit K is stuck in epoxide form
47
Warfarin inhibits biologically active factors
II, VII, IX, X
48
how long for warfarin to work
actively after <24hrs but takes 5-7 days for generation of coagulation factors incapable of binding Calcium
49
Warfarin administration
oral anticoagulant of choice
50
Warfarin Uses (3)
Prophylaxis for DVT & pulmonary embolism
Prosthetic Heart valves
Arterial thromboembolism prophylaxis in atrial fibrillation
51
Warfarin monitoring
INR VALUES Standardization of Prothrombin time
52
Warfarin Adverse Effects
Bleeding
53
Warfarin adverse rxns occur with (4)
Change in absorption and/or metabolism of Warfarin
Change in synthesis and/or catabolism of Vitamin K or coagulation factors (decreased hepatic function)
Changes in platelet function
Alteration in fibrin degradation
54
Warfarin genetic varients
CYP2C9 and VKORC genes
55
reduce warfarin dose by 30% in
Hetero or homozygotes for CYP2C9*2
heterozygous for CYP2C9*3
56
reduce warfarin dose by 90% in
Homozygote CYP2C9*3
57
VKORC1 G allele
A allele synthesize less VKORC1
less protein for warfarin to bind
58
Drugs that increase warfarin effects (6)
```
Aspirin
Ketoconazole & erythromycin
Cimetidine
Ibuprofen
Cephalosporins
Sulfamethoxazole/trimethoprim
```
59
Drugs that decrease warfarin effects (4)
Cholestyramine
Rifampin
Phenobarbital
Cigarette smoking
60
Warfarin contraindications
Presence of bleeding disorder or active bleeding site
61
can warfarin be given to pregnant women
no
62
Warfarin 1st trimester
nasal hypoplasia
63
Warfarin 2nd and 3rd trimester
CNS, increased fetal death
64
Tx of excessive bleeding
Whole blood or plasma
VitK - takes 24 hrs
65
Direct Thrombin Inhibitors (2)
ARGATROBAN (iv)
DABIGATRAN (ora)
66
Argatroban MOA
directly block site on thrombin
67
Argatroban adminstration
IV
68
Argatroban use (2)
pts at risk of heparin induce thrombocytopenia
coronary artery thrombosis
69
Dabigatran Etexilate Mesylate (DEM) is a
Anticoagulant –direct thrombin inhibitor
70
DEM MOA
affinity for free and fibrin bound thrombin
71
DEM administration
oral
72
DEM is converted to --- by plasma esterases
Dabigatran
73
DEM uses (2)
prophylaxis DVT and thromboembolism
74
DEM metabolites
4 Glucuronide metabolites (active)
75
is DEM a p450 substrate
no - less drug interactions
76
DEM is a substrate for
P-glycoprotein
77
DEM is excreted in
urine - must have good kidney function
78
Antidote for DEM associated excess bleeding
Idarucizumab
79
Idarucizumab MOA
Humanized monoclonal antibody binds to dabigatrin
350x higher affinity dabigatrin> thrombin
80
Direct factor Xa inhibitors (2)
Rivaroxaban and Apixaban
81
Rivaroxaban and Apixaban MOA
bind directly to factor Xa
prevent Xa cleaving prothrombin to thrombin
82
Rivaroxaban and Apixaban administration
oral
83
Rivaroxaban and Apixaban substrates for
CYP3A4
P-glycoprotein
84
Rivaroxaban and Apixaban uses (3)
Tx DVT and embolism
Prevent DVT after hip/knee replacement
Decrease risk of stroke in nonvalvular atrial fibrillation
85
Rivaroxaban and Apixaban side effects
BLACK BOX WARNING:
Bleeding can be life threatening
Bruising
86
Rivaroxaban and Apixaban antidote
Andexanet
recombinant factor Xa
87
Rivaroxaban and Apixabanc contraindications
active bleeding site
88
antiplatelet drugs (7)
Aspirin
Dipyridamole
Clopidogrel
Abciximab
Eptifibatide
Cangrelor
Tirofiban
89
Aspirin MOA
irreversible inhibitor of COX-1 and 2
Acetylates enzyme - thromboxane
90
Aspirin goal
inhibit platelet prostaglandin formation
91
Aspirin use
reduce risk of 2nd heart attack
92
Aspirin adverse effects
bleeding, GI irritation, GI ulcers
93
Dipyridamole MOA
inhibits phosphodiesterase increases platelet cAMP levels
94
Dipyridamole use
combination with other agents, very little benefit when used alone
Combined with warfarin
95
Clopidogrel is a platelet ---
Platelet ADP Aggregation Inhibitors
irreversible inhibitor
96
Clopidogrel is a prodrug that is metabolized to
thiol metabolite
97
Clopidogrel MOA
Bind Irreversibly to ADP P2Y12 receptor on platelets
Inhibits ADP activation of IIb/IIIa complex needed for platelet aggregation
98
Clopidogrel uses
prophylaxis for thrombosis
99
reverse Clopidogrel
must generate new plataletes
100
Clopidogrel side effects
bleeding
| Thrombocytopenia purpura risk
101
Clopidogrel monitoring
Monitor WBC and platelets
102
Cangrelor MOA
reversible P2Y12 platelet receptor inhibitor
103
Cangrelor administration
IV
104
Cangrelor half life
6 minutes - effect reverse within 1 hr
105
Platelet glycoprotein IIb/IIIa receptor antagonists (2)
Abciximab
Eptifibatide
106
Abciximab MOA
monoclonal antibody Fab fragment) construct of receptor
Ab binds to IIb/IIIa receptor
107
Eptifibatide is a
peptide derivative
108
what is more effective Abciximab or Eptifibatide
Abciximab
109
Abciximab and Eptifibatide administration
IV
110
Abciximab and Eptifibatide uses
Prevent thrombotic occurrence in patients with unstable angina or undergoing angioplasty
111
Tirofiban is a
PLATELET GLYCOPROTEIN IIb/IIIa RECEPTOR ANTAGONISTS
non peptide
112
Tirofiban administered
IV
113
Platelet glycoprotein IIb/IIIa receptor antagonists MOA
Competitive reversible inhibitor of interaction of Von Willebrand factor and fibrinogen with glycoprotein IIb/IIIa receptor
prevent cross linking of fibrinogen with platalets
114
Platelet glycoprotein IIb/IIIa receptor antagonists adverse effects
high incidence of bleeding
History of hemorrhagic stroke
Surgery, trauma past 6 weeks
Thrombocytopenia
Cannot use with warfarin
115
Abciximab and Eptifibatide time of action
Abciximab (>24 h) action longer than Eptifibatide (4-6 h) and Tirofiban (8 h)
116
Fibrinolytic system is responsible for degrading --- during wound healing.
Fibrinolytic system is responsible for degrading fibrin during wound healing.
117
what degrades fibrin, clotting factors, and fibrinogen
Plasmin
118
Plasminogen is converted to PLASMIN by --- which is released by --- cells
Plasminogen is converted to PLASMIN by t-plasminogen activator (t-PA) which is released by endothelial cells
119
Streptokinase MOA
streptokinase combines with 1 molecule of Plasminogen to form a complex
Complex then converts a second molecule of Plasminogen to plasmin
120
Streptokinase use
reperfusion of occluded coronaries following an MI, works best if used within 4-6 hr of chest pain
Pulmonary embolism
Deep vein Thromboembolism
Arterial thrombosis
121
Streptokinase adverse effects
33% of people develop fever
BLEEDING
LYTIC STATE excessive bleeding, circulating plasmin exceeds capacity of α2-antiplasmin
Highly antigenic
122
Streptokinase contraindications
Surgery or trauma in past 10 days
Pre-existing bleeding disorder (GI ulcer, retinal bleeding)
Diastolic pressure >110 mm Hg
Intracranial trauma
123
Anistreplase
Combination of streptokinase and plasminogen with catalytic site acylated
Acyl removed by plasma enzymes
Designed to provide more specific binding to fibrin
Less lytic state
124
Anistreplase t-plasminogen activator (rt-PA)
high affinity for fibrin, more rapid binding to fibrin and activation of fibrin bound plasminogen
Low activity for circulating plasminogen
125
t-PA directly activates --- to ---
t-PA directly activates plasminogen to plasmin
126
Anistreplase t-plasminogen activator (rt-PA) uses
```
•
Reperfusion of coronary arteries following an MI
•
Pulmonary embolism
•
Thrombotic stroke, use within 3 hrs
```
127
Tenecteplase
Genetically engineered derivative of alteplase
128
Tenecteplase Vs alteplase
More specific binding to fibrin
More resistant to PAI-1
Longer half-life
Higher incidence of reperfusion and functional outcome than alteplase for ischemic stroke treated
129
Thrombolytics adverse rxns
- inducing a hypocoagulable state
- patients bruise very easily
- any bleeding is difficult to stop
130
Aminocaproic Acid
Inhibitor of fibrinolysis
Lysine analog competes for lysine binding sites on plasminogen and plasmin
Inhibits interaction of plasmin and fibrin
