Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Therapeutics 2 Exam 4 -Geriatric, Coagulation > Drugs Used in Coagulation Disorders (Hock) > Flashcards

Drugs Used in Coagulation Disorders (Hock) Flashcards

1
Q

What 4 types of drugs are used in coagulation disorders?

A

-Antiplatelets
-Anticoagulants
-Thrombolytics
-Coagulants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is hemostasis?

A

The arrest of bleeding from a damaged blood vessel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the five stages of hemostasis?

A
  1. Injury to blood vessel
  2. Vasospasm
    (blood vessel constricts to reduce blood flow through vessel which minimizes bleeding)
  3. Platelet Plug Formation
    (platelets form temporary plug, platelet adherence and aggregation)
  4. Fibrin clot formation
    (reinforced by fibrin)
  5. Fibrinolysis
    (pathway clears away the clot/plug)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What molecules are involved in the creation of fibrin during clot formation?

A

Prothrombin -> Thrombin

Thrombin then cleaves Fibrinogen -> Fibrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What molecules are involved in the break down of fibrin during fibrinolysis?

A

Plasminogen -> Plasmin

Plasmin then splits Fibrin -> Split Products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What cells are platelets derived from?

A

Megakaryocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

True or False: Platelets do not have a nucleus

A

TRUE
They have organelles and secretory granules but no nucleus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How to platelets replicate?

A

Platelets do not divide

-they just get bigger until they send out processes that pinch off into pre-platelets
-these are then broken down into small platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does not having a nucleus affect platelet’s ability to fix themselves?

A

Platelets do not have DNA or RNA and therefore cannot make proteins

-Because of this, they are unable to replace proteins that have been inhibited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What initiates platelet reactions?

A

Contact with the extracellular matrix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

After injury to a blood vessel occurs and platelets come into contact with the extracellular matrix, what are the 3 processes that mediate platelet adhesion to the extracellular membrane?
(First Step of Platelet Activation)

A

-GP la on the platelet binding to collagen

-GP lb on the platelet binding to von Willebrand Factor bridged to collagen

-Shape changes that facilitate receptor binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

When platelets aggregate to the extracellular matrix after injury occurs, GP la (on the platelet) mediates adhesion by binding to what?

A

collagen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

When platelets aggregate to the extracellular matrix after injury occurs, GP lb (on the platelet) mediates adhesion by binding to what?

A

von Willebrand Factor bridged to collagen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do intact endothelial cells inhibit thrombogenesis (blood clot formation)?

A

They secrete PGI2 (prostacyclin)

-prostacyclin inhibits platelet aggregation and increases vasodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What occurs during the second step of platelet activation?

A

Secretion
-Degranulation

-Platelet granules are released:
—ADP
—Thromboxane A2 (TXA2)
—Serotonin (5-HT)

*These granules are released from platelets and activate + recruit other platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Besides recruiting other platelets during platelet activation, what is the other function of Thromboxane A2 (TXA2) and Serotonin (5-HT)?

A

Vasoconstrictors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What happens during the third step of platelet activation?

A

-The actual aggregation itself

-ADP, 5-HT, and TXA2 granules induce a conformational change of GPIIb/IIIa receptors (on platelets) which causes them to bind fibrinogen

-The fibrinogen cross-links the platelets to form a temporary hemostatic plug

-The platelets contract and form a mass (irreversible)

-Fibrin stabilizes and anchors the mass to form a surface for clot formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the role of fibrinogen in clot formation?

A

Cross-links platelets into a temporary hemostatic plug that eventually fuses into a mass

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the role of fibrin in clot formation?

A

Fibrin stabilizes and anchors the mass of platelets formed by fibrinogen to form a surface for clot formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What molecule is responsible for changing fibrinogen into fibrin?

A

Thrombin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What molecule is responsible for changing prothrombin into thrombin?

A

Factor Xa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the 5 kinds of antiplatelet drugs?

A

COX-1 Inhibitors

ADP Receptor Inhibitors

Blockers of GPIIb/IIIa receptors

Phosphodiesterase-3 Inhibitors

Protease-Activated Receptor Inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the main COX-1 inhibitor used?

A

Aspirin (ASA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How do COX-1inhibitors work? (Aspirin)

A

-Inhibits platelet COX-1 irreversibly through acetylation
(platelets cannot fix this without a nucleus)

-Interferes with platelet aggregation

-Prolongs bleeding time

Prevents arterial thrombi from forming

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is key to the anti-platelet activity of aspirin?

A

Inhibition of TXA2 granule (Thromboxane A2)
*interferes with platelet aggregation and loss of vasoconstriction effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How does aspirin (COX-1 Inhibitor) inhibit the TXA2 granule?

A

The permanent loss of platelet COX-1 activity caused by aspirin results in decreased TXA2 levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What dosing of aspirin gives its maximal effect?

A

50-320mg per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is prostacyclin (PGI2) and how can it be affected by aspirin?

A

Prostacyclin (PGI2) is produced by COX-2 in endothelial cells and secreted to inhibit thrombogenesis (see other card)

-Production of prostacyclin in tissues can be inhibited with high doses of aspirin

**We do not want this because prostacyclin helps with anti-coagulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the indications for use of aspirin (COX-1 Inhibitor)?

A

Prophylaxis and treatment of arterial thromboembolic disorders:

-Prevent coronary thrombosis in unstable angina (restricted blood flow to heart)

-Adjunct to thrombolytic therapy

-Reduce recurrence of thrombotic stroke

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the clinical actions of aspirin (COX-1 Inhibitor)?

A

-Prolongs bleeding time

*No change in prothrombin time (PT) (how long it takes for a clot to form)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How long after the last dose of aspirin is given does it take for hemostasis (body’s natural way of stopping bleeding) to return to normal?

A

36 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the side effects of aspirin?

A

-Upper GI Bleeding
(due to inhibition of COX1 produced prostaglandins in the GI tract that protect the stomach from acid)
*risk increases with age, NSAID use, and alcohol

-Acute Aspirin Overdose
(Symptoms: nausea, vomiting, diarrhea, fever, coma, death)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What doses of aspirin can induce Acute Aspirin Overdose?

A

Doses above 150 mg/kg

**Doses above 500 mg/kg can be fatal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Why did selective COX-2 inhibitors not work?

A

COX-2 makes prostacyclin in endothelial cells which leads to vasodilation and inhibition of platelet aggregation

COX-1 produces thromboxane A2 in platelets which lead to vasoconstriction and platelet aggregation (what we want to block)

Selective COX-2 inhibitors were blocking prostacyclin synthesis (blocking the anti-coagulation effects) and not preventing TXA2 synthesis

**This increased the cardiovascular risk!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What are the two ADP receptors involved in platelet activation?

A

P2Y1

P2Y12

**Both of these must be activated to activate platelets, so you can inhibit just one!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are the 4 ADP receptor inhibitors?

A

Pro-Drug:
-Clopidogrel
-Prasugrel

Direct Acting:
-Ticagrelor
-Cangrelor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is the mechanism of action of Clopidogrel (Plavix)?

A

P2Y12 ADP receptor inhibitor (on platelet surface)
—irreversibly blocks the ADP receptor and subsequent activation of the GPIIb/IIa complex

*reduces platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How is clopidogrel (Plavix) taken?

A

Orally

39
Q

How long does the action of clopidogrel (Plavix) last after the last dose?

A

Several days

40
Q

What drug class is clopidogrel (Plavix) in?

A

Thienopyridine class of ADP receptor inhibitors
(Pro-drugs)

41
Q

What are the uses of clopidogrel (Plavix)?

A

-Acute Coronary Syndrome
-Recent MI
-Stroke
-Established peripheral vascular disease and coronary stent procedures

**The standard care for MI and STENT placement

42
Q

What drug class is prasugrel (Effient)?

A

*Also a thienopyridine (same as clopidogrel)

(Pro-drug)

43
Q

How is prasugrel (Effient) activated?

A

Esterases + CYP 3A4/2B6 cleave the ester bond to the active form

44
Q

What is the mechanism of action of Prasugrel (Effient)?

A

Irreversibly binds P2Y12 receptor (same as clopidogrel)

45
Q

What is prasugrel (Effient) used to treat?

A

-Acute Coronary Syndrome
-Percutaneous coronary intervention (PCI)

46
Q

How is prasugrel (Effient) taken?

A

Orally
(same as clopidogrel)

47
Q

What are some added considerations associated with Prasugrel (Effient) use?

A

-HIGH BLEEDING RISK
*do not use in elderly or before CABG (coronary artery bypass graft)

48
Q

Why does Prasugrel (Effient) have a high bleeding risk?

A

It is not able to be reversed quickly

49
Q

What is the ADP receptor inhibitor Ticagrelor (Brilinta) used to treat?

A

-Acute Coronary Syndrome
-PCI (STENT Placement)

50
Q

How is Ticagrelor (Brilinta) taken?

A

Orally

51
Q

What is an advantage of the ADP receptor inhibitors Ticagrelor (Brilinta) and Cangrelor (Kangreal) over Prasugrel (Effient) and Clopidogrel (Plavix)?

A

Ticagrelor and Cangrelor DO NOT REQUIRE bioactivation which lets them work very quickly in the body

52
Q

Which ADP receptor inhibitors have reversible binding and which have irreversible binding?

A

Reversible:
-Ticagrelor
-Cangrelor

Irreversible:
-Clopidogrel
-Prasugrel

**the drugs not requiring bioactivation bing reversible

**the pro-drugs bind irreversibly

53
Q

What is the onset of action of Ticagrelor (Brilinta)?

A

7-9 hours
(faster than clopidogrel)

54
Q

What is Ticagrelor (Brilinta) the substrate of?

A

CYP3A4

55
Q

What are some extra considerations for Ticagrelor (Brilinta)?

A

RISK OF BLEEDING

*do not use immediately before coronary artery bypass graft
(same as Prasugrel)

56
Q

What is the mechanism of action for the ADP receptor Cangrelor (Kangreal)?

A

Reversibly inhibits P2Y12 receptors

57
Q

What is Cangrelor (Kangreal) used for?

A

Adjunct to PCI (percutaneous coronary intervention) to prevent thrombosis

-procedure that treats narrowed arteries in the heart

58
Q

How is cangrelor (Kangreal) given?

A

IV
***only one not oral

59
Q

What is the onset of action of cangrelor (Kangreal)?

A

VERY FAST
half-life: 3-5 mins

**because it is given IV
**not a concern if patient is needing surgery

60
Q

What CYP activates Clopidogrel?

A

CYP2C19

61
Q

What CYP’s activate Prasugrel?

A

CYP3A4 and CYP2B6

62
Q

What are the 3 GPIIb/IIIa receptor inhibitors?

A

Abciximab

Eptifibitide

Tirofiban

63
Q

What is the mechanism of action of GPIIb-IIIa receptor inhibitors?

A

Inhibit fibrinogen crosslinking of platelets

(since fibrinogen binds to the GPIIb-IIIa sites on platelets)

64
Q

What is Abciximab (ReoPro)?

A

Fab fragment of chimeric mouse-human monoclonal antibody

-Binds GPIIb-IIIa to prevent platelet aggregation

65
Q

What is Eptifibitide (Integrilin)?

A

A synthetic peptide (derived from cyclic heptapeptide derived from rattlesnake venom)

-Selectively blocks GPIIb-IIIa REVERSIBLY

66
Q

What is Tirofiban (Aggrastat)?

A

A nonapeptide tyrosine analogue

Works the same as eptifibatide

-Reversibly inhibits fibrinogen binding to GPIIb/IIIa

67
Q

How is Abciximab (ReoPro) administered?

A

IV bolus followed by infusion

68
Q

What is the duration of action of Abciximab (ReoPro)?

A

LONG

69
Q

How does the duration of action of Abciximab (ReoPro) affect risk of bleeding?

A

Abciximab has a long half life which increases the risk of bleeding

70
Q

What is Abciximab used for?

A

-To prevent thromboembolism in coronary angioplasty

-Combined with t-PA for early acute MI treatment

71
Q

What are some additional considerations with Abciximab (ReoPro)?

A

-Not readily reversible so increased bleeding risk

-Takes 42 hours to see platelet activity come back (prolonged effect)

72
Q

How is Eptifibatide (Integrilin) administered?

A

IV bolus followed by infusion (up to 72 hours)

73
Q

What is the duration of action of Eptifibatide (Integrilin)?

A

SHORT
6-12 hr

74
Q

What is Eptifibatide (Integrilin) used for?

A

-Prevent thromboembolism in unstable angina and angioplastic coronary procedures (STENTs)

75
Q

What amino acids make Eptifibatide (Integrilin) a perfect mimic of fibrinogen?

A

R (arginine)
G (glycine)
D (aspartic acid)

76
Q

How is Tirofiban (Aggrastat) administered?

A

IV in dilute solution (10-25 ug/kg initial)

77
Q

What are some important considerations for tirofiban (Aggrastat) and how quickly it works?

A

> 90% inhibition of platelet aggregation after 30min infusion (VERY RAPID)

*2 hr half life

78
Q

What is Tirofiban (Aggrastat) used to treat?

A

Acute Coronary Syndrome

79
Q

How does tirofiban (Aggrastat) mimic fibrinogen?

A

Mimics the glycine (G) and aspartic acid (D) side chains

works the same as eptifibatide

80
Q

What are the 2 phosphodiesterase-3 inhibitors?

A

Dipyridamole -PDE5 inhibitor (and 3 to lesser extent)

Cilostazole -PDE3 inhibitor

81
Q

How do Phosphodiesterase-3 Inhibitors work?

A

-Inhibit platelet aggregation

-Inhibit cAMP PDE (opposing P2Y12 action) and adenosine uptake

82
Q

What are the uses for Dipyridamole (Persantine)?

A

Combo with warfarin: Prevent embolization from prosthetic heart valves

Combo with ASA: Prevent cerebrovascular ischemia (stroke)

83
Q

What is the use for Cilostazol (Pletal)?

A

Intermittent claudication

(a decrease in blood flow to the lower extremities due to atherosclerosis)

*prevents platelet aggregation that would further block blood flow

84
Q

What is the mechanism of action for Protease Activated Receptor (PAR) Inhibitors?

A

*Thrombin cleaves the N terminus of PAR-1 to create its active form which activates platelets

Inhibitors cleave PAR-1 receptors on platelets so that they cannot be activated by thrombin. This prevents activation.

85
Q

Besides platelet activation, what other function do PARs have?

A

PARs are G-protein coupled receptors involved in the release of calcium from storage

86
Q

What is the singular Protease Activated Receptor (PAR) inhibitor?

A

Vorapaxar

87
Q

What are the main purposes of thrombin?

A

-Changes fibrinogen into fibrin

-Also cleaves acts as a protease to cleave the N terminus of PAR1 to create its active form. This activates platelets

88
Q

How is Vorapaxar (Zontivity) taken?

A

Orally

89
Q

What is Vorapaxar (Zontivity) used to treat?

A

Prophylactic to:
–Prevent thrombosis in patients with previous MI or peripheral artery disease (PAD)

90
Q

Is Vorapaxar (Zontivity) used alone?

A

NO
-Used in combo with aspirin or clopidogrel

91
Q

What contraindications are associated with Vorapaxar (Zontivity)?

A

-History of stroke
-TIA’s (mini stroke)
-Intracranial hemorrhage

92
Q

What is the duration of action of Vorapaxar (Zontivity)?

A

3-4 days

*antiplatelet effect persists for days after discontinuation (long)

93
Q

What CYP metabolizes Vorapaxar (Zontivity)?

A

Metabolized by CYP3A4

**avoid concurrent use with strong CYP 3A4 inhibitors OR inducers

Therapeutics 2 Exam 4 -Geriatric, Coagulation (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions