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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
Q

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

A

b. VIIIa; X

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26
Q

is the extrinsic pathway for coagulation fast or slow?

A

fast (~15 seconds to start clot formation)

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27
Q

thrombin converts fibrinogen into fibrin. It also activates factor ___ which then cross-links fibrin to form a stable clot incorporated into platelet plug

A

XIII

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28
Q

thrombin and platelet activation __________ coagulation

a. inc
b. dec

A

a. inc

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29
Q

platelet activation increases activation of factors ___ and ___ and cleavage of __________

A

VII; X; prothrombin

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30
Q

antithrombin, the protein C system, and factor Xa __________ coagulation

a. inc
b. dec

A

b. dec

31
Q

antithrombin neutralizes pro-coagulant ser proteases (thrombin, Xa, IXa); the reaction is accelerated by __________

A

heparin

32
Q

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

A

thrombomodulin; S

33
Q

factor Xa activates _____ to block initial activation of factor VII

a. t-PA
b. TFPI

A

b. TFPI (tissue factor pathway inhibitor)

34
Q

INR formula (idk if this matters)

A

(PTtest/PTnorm)^ISI

(normal PT time is 11-14 sec; ISI will be given on bottle)

35
Q

normal INR range?
therapeutic INR range?

A

normal: 0.8-1.2
therapeutic: ~2-3

(> 3 risk of hemorrhage)

36
Q

warfarin acts by inhibiting the synthesis of which 4 clotting factors?

A

II, VII, IX, and X (2, 7, 9, 10)

37
Q

warfarin inhibits what enzyme?

A

Vitamin K-epoxide reductase (VKORC1)

(this blocks reduction of Vit K epoxide back to its active form)

38
Q

which vitamin is essential for post-translation modification of clotting factors VII, IX, X, prothrombin (II) and anticoagulation proteins C and S?

A

vitamin K

39
Q

warfarin’s max anticoagulant effects will be observed ___-___ days after start of therapy

A

3-5

40
Q

warfarin is metabolized in the liver by which CYP?

A

CYP2C9

41
Q

warfarin overdose: what can we administer for a iatrogenic hemorrhage?

A

vitamin K1 (can activate warfarin-inhibited reductase)

42
Q

warfarin overdose: what can we give if there is a serious hemorrhage?

A

plasma (replaces clotting factors faster than Vit K therapy)

43
Q

true or false: warfarin can be used in pregnancy

A

false

44
Q

warfarin necrosis develops when which protein is deficient?

A

protein C

(could also be protein S)

45
Q

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

A

b. IV

46
Q

examples of low molecular weight heparins (2 of them)

A

enoxaparin, daltaparin

47
Q

example of a non-heparinoid that is an indirect factor IIa/Xa inhibitor

A

fondaparinux

48
Q

how does heparin work?

A

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
Q

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

A

c. factor Xa

50
Q

treatment for iatrogenic hemorrhage due to heparin (heparin reversal agent)

A

stop heparin and give protamine sulfate (heparin inhibitor)

51
Q

broad-spectrum antibiotics _______ warfarin’s anticoagulation effect

a. enhance
b. diminish

A

a. enhance

52
Q

what is exogenous vitamin K and Kcentra used for?

A

reversal effect for warfarin

53
Q

what is the active unit in heparin?

A

it is the active pentasaccharide unit

54
Q

which has the highest risk of heparin-induced thrombocytopenia?

a. LMWH
b. UFH
c. fondaparinux

A

b. UFH

HIT risk: UFH > LMWH > fondaparinux

55
Q

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

A

d. dabigatran

56
Q

true or false: protamine sulfate reverses the effects of heparin and fondaparinux

A

false (not fondaparinux)

57
Q

what is a potential adverse effect seen in extended therapy with heparin (3-6 months)?

A

osteoporosis

58
Q

which group on the pentasaccharide unit of heparin is required for binding to antithrombin?

A

sulfate groups (neg charge)

59
Q

true or false: UFH and LMWH are both subQ only

A

false (LMWH is subQ only, UFH is IV or subQ)

60
Q

fondaparinux mechanism and half life range

A

mechanism: indirectly inhibits factor Xa by selectively binding antithrombin
t1/2: 17-21 hours

61
Q

fondaparinux uses (2)

A

-VTE
-prophylaxis in pts undergoing hip or knee replacement, or abdominal surgery

62
Q

which should not be used if CrCl > 95 mL/min?

a. rivaroxaban
b. apixaban
c. edoxaban
d. dabigatran

A

c. edoxaban

63
Q

andexanet is the reversal agent for what two drugs?

A

apixaban and rivaroxaban

64
Q

black box warning for andexanet: inc risk of __________ events

A

thromboembolic

65
Q

what parts of thrombin can DTIs bind to? (2)

A

-active site of thrombin
-exosite of thrombin

(or both)

66
Q

lepirudin is a DTI used in the treatment of _____

A

HIT (heparin induced thrombocytopenia)

67
Q

hirudin is a peptide derived from what animal?

A

medicinal leech

68
Q

which drug has irreversible binding?

a. lepirudin
b. bivalirudin
c. argatroban

A

a. lepirudin

(bivalent binding at active site and exosite I of thrombin)

69
Q

bivalirudin (angiomax) is given IV during what procedure?

A

percutaneous coronary angioplasty

70
Q

what bond in bivalirudin (angiomax) is cleaved by thrombin?

a. ser-pro
b. arg-pro
c. gly-asn
d. pro-asp

A

b. arg-pro

(short duration of action bc it is cleaved at this site)

71
Q

true or false: bivalirudin induces antibody formation

A

false

72
Q

argatroban binds reversibly to the active site of __________

A

thrombin

73
Q

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

a. percutaneous coronary angioplasty

PHRM 844 Therapeutics (28 decks)

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