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PHRM 844 Therapeutics > Exam 4 - Anticoagulant Drugs > Flashcards

Exam 4 - Anticoagulant Drugs Flashcards

1
Q

thrombin is an enzyme that converts __________ to __________

A

fibrinogen; fibrin

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2
Q

factors XII, XI, X, IX, VII, II are _____-coagulants

a. pro
b. anti

A

a. pro

(these cleave down-stream factors to activate them)

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3
Q

thrombin is

a. factor XIII
b. factor XII
c. factor IIa
d. factor II

A

c. factor IIa

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4
Q

what cleaves factors Va and VIIIa?

a. anti-thrombin III
b. factor V
c. protein S
d. protein C

A

d. protein C

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5
Q

factors VIII, V, III (tissue factor), and protein S are glycoproteins. What is their general function?

A

they are co-factors for activation of proteases

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6
Q

what binds to and inhibits thrombin?

A

anti-thrombin III

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7
Q

Ca2+ is which factor?

a. II
b. III
c. IV
d. V

A

c. IV

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8
Q

function of factor IV

a. cross-links fibrin fibers (factor XIII)
b. links certain factors to phospholipid membranes
c. cleave factors Va and VIIIa

A

b. links certain factors to phospholipid membranes

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9
Q

transglutaminase function

a. cross-links fibrin fibers (factor XIII)
b. links certain factors to phospholipid membranes
c. cleave factors Va and VIIIa

A

a. cross-links fibrin fibers (factor XIII)

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10
Q

what is the substrate protein for factor IIa (thrombin) that polymerizes to form clot?

A

fibrinogen/fibrin

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11
Q

hemophilia A is a deficiency in factor

a. IX
b. VIII
c. IIa

A

b. VIII

(factor 8)

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12
Q

hemophilia B is a deficiency in factor

a. IX (9)
b. VIII (8)
c. IIa (2a)

A

a. IX (9)

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13
Q

is hemophilia A and B more prevalent in males or females?

A

males (they are X-linked)

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14
Q

which is more common, hemophilia A or B?

A

A

(A -> 1 in 5000 males, B -> 1 in 25000 males)

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15
Q

what does factor V Leiden do?

A

makes factor V resistant to cleavage by protein C

(it is an inherited clotting disorder that can inc chance of developing abnormal blood clots)

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16
Q

what is the only clotting factor that is NOT made in the liver?

A

von Willebrand factor

(produced in endothelium, subendothelium, and megakaryocytes; factor VIII is also produced in the endothelium)

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17
Q

which of these describes the extrinsic pathway of coagulation?

a. Requires a factor (Tissue Factor) extrinsic to the blood; important when vessel is damaged and blood leaks out
b. Triggered when collagen is exposed on the wall of the blood vessel

A

a. Requires a factor (Tissue Factor) extrinsic to the blood; important when vessel is damaged and blood leaks out

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18
Q

which of these describes the intrinsic pathway of coagulation?

a. Requires a factor (Tissue Factor) extrinsic to the blood; important when vessel is damaged and blood leaks out
b. Triggered when collagen is exposed on the wall of the blood vessel

A

b. Triggered when collagen is exposed on the wall of the blood vessel

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19
Q

the _____ pathway of coagulation is initiated by contact with negatively charged collagen of diseased or injured blood vessel

a. extrinsic
b. intrinsic

A

b. intrinsic

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20
Q

the _____ pathway of coagulation is initiated by release of tissue thromboplastin

a. extrinsic
b. intrinsic

A

a. extrinsic

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21
Q

activation of which factor is important for the intrinsic pathway?

A

factor 9

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22
Q

what factor is the common point for the intrinsic and extrinsic pathway?

A

factor X

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23
Q

extrinsic pathway: _____ binding to factor VII activates it

A

TF (tissue factor)

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24
Q

extrinsic pathway: factor VIIa binds and cleaves which factor?

A

factor X

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25
convergence with intrinsic pathway: factor IXa binds factor ___ on the surface of platelets and activates factor ___ a. XII; X b. VIIIa; X c. IX; X d. IV; IIIa
b. VIIIa; X
26
is the extrinsic pathway for coagulation fast or slow?
fast (~15 seconds to start clot formation)
27
thrombin converts fibrinogen into fibrin. It also activates factor ___ which then cross-links fibrin to form a stable clot incorporated into platelet plug
XIII
28
thrombin and platelet activation __________ coagulation a. inc b. dec
a. inc
29
platelet activation increases activation of factors ___ and ___ and cleavage of __________
VII; X; prothrombin
30
antithrombin, the protein C system, and factor Xa __________ coagulation a. inc b. dec
b. dec
31
antithrombin neutralizes pro-coagulant ser proteases (thrombin, Xa, IXa); the reaction is accelerated by __________
heparin
32
the protein C system is activated by thrombin binding to __________. The activated protein C complex (APC) forms a complex with protein ___ to inactivate factors Va and VIIIa
thrombomodulin; S
33
factor Xa activates _____ to block initial activation of factor VII a. t-PA b. TFPI
b. TFPI (tissue factor pathway inhibitor)
34
INR formula (idk if this matters)
(PTtest/PTnorm)^ISI (normal PT time is 11-14 sec; ISI will be given on bottle)
35
normal INR range? therapeutic INR range?
normal: 0.8-1.2 therapeutic: ~2-3 (> 3 risk of hemorrhage)
36
warfarin acts by inhibiting the synthesis of which 4 clotting factors?
II, VII, IX, and X (2, 7, 9, 10)
37
warfarin inhibits what enzyme?
Vitamin K-epoxide reductase (VKORC1) (this blocks reduction of Vit K epoxide back to its active form)
38
which vitamin is essential for post-translation modification of clotting factors VII, IX, X, prothrombin (II) and anticoagulation proteins C and S?
vitamin K
39
warfarin's max anticoagulant effects will be observed ___-___ days after start of therapy
3-5
40
warfarin is metabolized in the liver by which CYP?
CYP2C9
41
warfarin overdose: what can we administer for a iatrogenic hemorrhage?
vitamin K1 (can activate warfarin-inhibited reductase)
42
warfarin overdose: what can we give if there is a serious hemorrhage?
plasma (replaces clotting factors faster than Vit K therapy)
43
true or false: warfarin can be used in pregnancy
false
44
warfarin necrosis develops when which protein is deficient?
protein C (could also be protein S)
45
for emergent situations where the effects of warfarin need to be reversed immediately, exogenous vitamin K along with prothrombin complex concentrates (factors II, VII, IX, and X with proteins C and S; Kcentra) are administered a. orally b. IV c. subQ d. IM
b. IV
46
examples of low molecular weight heparins (2 of them)
enoxaparin, daltaparin
47
example of a non-heparinoid that is an indirect factor IIa/Xa inhibitor
fondaparinux
48
how does heparin work?
acts by accelerating antithrombin (AT) rxns to inactivate thrombin and factor Xa (binds to AT -> conformational change of the protein and allows formation of a heparin-AT-target factor. The conformation change inc the interaction of AT with the target factors)
49
LMWH are too small to bind AT and thrombin, so they have greater specificity for inhibition of which factor? a. factor II b. factor VIIIa c. factor Xa d. factor X
c. factor Xa
50
treatment for iatrogenic hemorrhage due to heparin (heparin reversal agent)
stop heparin and give protamine sulfate (heparin inhibitor)
51
broad-spectrum antibiotics _______ warfarin's anticoagulation effect a. enhance b. diminish
a. enhance
52
what is exogenous vitamin K and Kcentra used for?
reversal effect for warfarin
53
what is the active unit in heparin?
it is the active pentasaccharide unit
54
which has the highest risk of heparin-induced thrombocytopenia? a. LMWH b. UFH c. fondaparinux
b. UFH HIT risk: UFH > LMWH > fondaparinux
55
what drug does not have a risk of hematoma/paralysis in pts undergoing spinal puncture or epidural anesthesia? a. apixaban b. rivaroxaban c. edoxaban d. dabigatran
d. dabigatran
56
true or false: protamine sulfate reverses the effects of heparin and fondaparinux
false (not fondaparinux)
57
what is a potential adverse effect seen in extended therapy with heparin (3-6 months)?
osteoporosis
58
which group on the pentasaccharide unit of heparin is required for binding to antithrombin?
sulfate groups (neg charge)
59
true or false: UFH and LMWH are both subQ only
false (LMWH is subQ only, UFH is IV or subQ)
60
fondaparinux mechanism and half life range
mechanism: indirectly inhibits factor Xa by selectively binding antithrombin t1/2: 17-21 hours
61
fondaparinux uses (2)
-VTE -prophylaxis in pts undergoing hip or knee replacement, or abdominal surgery
62
which should not be used if CrCl > 95 mL/min? a. rivaroxaban b. apixaban c. edoxaban d. dabigatran
c. edoxaban
63
andexanet is the reversal agent for what two drugs?
apixaban and rivaroxaban
64
black box warning for andexanet: inc risk of __________ events
thromboembolic
65
what parts of thrombin can DTIs bind to? (2)
-active site of thrombin -exosite of thrombin (or both)
66
lepirudin is a DTI used in the treatment of _____
HIT (heparin induced thrombocytopenia)
67
hirudin is a peptide derived from what animal?
medicinal leech
68
which drug has irreversible binding? a. lepirudin b. bivalirudin c. argatroban
a. lepirudin (bivalent binding at active site and exosite I of thrombin)
69
bivalirudin (angiomax) is given IV during what procedure?
percutaneous coronary angioplasty
70
what bond in bivalirudin (angiomax) is cleaved by thrombin? a. ser-pro b. arg-pro c. gly-asn d. pro-asp
b. arg-pro (short duration of action bc it is cleaved at this site)
71
true or false: bivalirudin induces antibody formation
false
72
argatroban binds reversibly to the active site of __________
thrombin
73
which is not a use of argatroban? a. percutaneous coronary angioplasty b. treatment of HIT c. treatment of coronary artery thrombosis in pts with HIT d. prophylaxis in PCI procedures
a. percutaneous coronary angioplasty

PHRM 844 Therapeutics (28 decks)

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