Brainscape's Knowledge GenomeTM

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


See full index

Pharm Test 4 > 10/28 > Flashcards

10/28 Flashcards

1
Q

What is thrombogenesis

A

formation of thrombi

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

What is hemostasis?

A

The ability of the body to stop itself from bleeding out

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

Part of hemostasis is _____________

A

thrombogenesis

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

what is fibrin?

A

a net that traps the platelet plugs and traps red blood cells at site of injury “glue”/”morter”

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

What happens when we have a larger injury in the vessels?(pharm)

A

it can expose collagen and (von Willebrand factor) vWF.
When these are exposed they act with glycoproteins that are on platelet cell surfaces and this sets up platelet coagulation or thrombogenesis
Eventually this will lead to clotting cascade

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

what is a red thrombus and where do they occur?

A

A lot of fibrin with a long tail and with RBC’s trapped in it that occurs in slow moving vessels like veins

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

what is a white thrombus?

A

a thrombus with more fibrinogen or platelets in it that occurs in high pressure arteries d/t damaged or plaque buildup in the endothelium

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

What is a thromboembolism?

A

a thrombus that has broken off of the vessel it was made it and is now moving through the body

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

what happens in response to damage of Blood vessels

A
  • vasoconstriction d/t serotonin
  • formation of platelet plugs
  • degranulation of platelet aggregation which leads to the activation of more platelets
  • That forms a fibrin clot
  • tight regulation of coagulation and fibrinolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the phases of platelets?

A

Adhesion
Aggregation
Secretion
Cross-linking of adjacent platelets

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

what causes adhesion?

A

Exposure of collagen and von willebrand factor cause platelets to adhere to surface

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

what is the secretion related to platelets?

A

They secrete substances,
primarily serotonin,
adenosine diphosphate,
and thromboxane A2
and they encourage additional cross linking of platelets

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

what is cross-linking?

A

formation this cross linked platelet clot or thrombocyte clot

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

Where does PGI2 aka prostacyclin come from?

A

The blood vessel lining is made up of endothelial cells which normally produce prostaglandin I2 or PGI2 (aka prostacyclin)

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

what does PGI2/prostacyclin do?

A

it inhibits platelet aggregation

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

When is PGI2 activated?

A

During the normal state of endothelial cell, if there’s no damage, is to inhibit platelet aggregation because we don’t want clots forming when there shouldn’t be clots forming

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

Why is there a black box warning for CV events on NSAIDs?

A

NSAIDs inhibit prostaglandin synthesis, so they are actually “proclot”

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

How does aspirin work?

A

aspirin targets specifically the platelets themselves by inhibiting thromboxane A2

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

what receptor does collagen bind to?

A

glycoprotein 1-A receptor.

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

what receptor does Von Willebrand factor bind to?

A

glycoprotein 1-B

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

what results in the activation and release of soluble mediators

A

Collagen binding to platelets at the glycoprotein 1-A receptor.
Von willebrand factor binding to platelets at the glycoprotein 1-B.

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

which soluble mediators are released d/t the binding of Collagen and vWF to platelets?

A
  1. adenosine (ADP)
  2. thromboxane A-2
  3. serotonin (5 HT)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the steps to platelet aggregation?

A
  1. Damage exposes collagen and von willebrand factor
  2. Collagen binds to platelets specifically at the glycoprotein 1-A receptor.
    Von willebrand factor binds to platelets at the glycoprotein 1-B receptor.
  3. adenosine(ADP), thromboxane A-2, and serotonin(5 HT) is released
  4. Serotonin causes vasoconstriction of smooth muscle on vessels and it binds to serotonin receptors on other platelets which activates those platelets.
    ADP and thromboxane A2 also bind to additional receptors on other platelets that are going to activate more platelets
  5. Once the second platelet is activated it degranulates and releases additional ADP, thromboxane A2 and 5 HT.

It’s a positive feedback mechanism where multiple platelets are going to join together to be cross linked into this network

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

what does fibrinogen do and where is it produced?

A

Fibrinogen turns into fibrin which holds platelets together! Fibrinogen is produced through the coagulation cascade.

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

what is required in order to form a stable clot that’s going to prevent us from bleeding out?

A

both platelet aggregation and coagulation cascade

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

what is the common pathway?

A

Where the intrinsic and extrinsic pathways meet in the coagulation cascade

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

What are the steps in the common pathway?

A
  1. Factor 10 is activated.
  2. Factor 10 activates the inactive form of thrombin (aka prothrombin) to its active form called thrombin.
  3. Thrombin increases the release of more thrombin, it activates platelets, and it converts the inactive form of fibrinogen into the active form of fibrin.
  4. Fibrin helps platelets aggregate together and it forms a mesh network to trap platelets.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the steps in the intrinsic pathway?

A

Damage to the surface activates factor XII(12)
XII activates factor XI(11)
XI activates factor IX(9)
IX + VIII(8) activates factor X(10)
this starts the common pathway

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

What are the steps in the extrinsic pathway?

A

Trauma activates factor VII(7)
VII activates factor X(10) this starts the common pathway

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

what is another name for the intrinsic pathway?

A

contact activation

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

what is another name for the extrinsic pathway?

A

Tissue factor

32
Q

What all does thrombin do when activated?

A
  1. It increases the release of more thrombin
  2. It activates platelets
  3. It converts the inactive form of fibrinogen into the active form of fibrin.
33
Q

Which number is the contact factor?

A

XII (12)

34
Q

which number is the tissue factor?

A

VII(7)

35
Q

What is Virchow’s triad?

A

stasis
endothelial injury
hypercoagulability

36
Q

What causes DVTs and PEs most often?

A

Red thrombi

37
Q

What are the inherited risk factors for DVTs?

A

Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
Sickle cell anemia
Activated protein C resistance

38
Q

What are the aquired risk factors for DVTs?

A

Bedridden
Surgery/trauma
Obesity
Estrogen use
Malignancies
Chronic venous insufficiency

39
Q

What is DIC?

A

Over stimulation of the blood clotting mechanism and risk of impaired blood flow

Clots are formed all over the body.
Using up all of the platelets and clotting factors which leads to spontaneous bleeding

40
Q

what is the mortality rate of DIC?

A

10% to 50%

41
Q

What causes DIC?

A
  • Massive tissue injury
  • Malignancy (cancers)
  • Bacterial sepsis / bacterial infection - usually gram negative bacteria b/c of endotoxins it produces
  • Abruptio placentae
42
Q

What are the treatments for DIC?

A

Plasma transfusions or transfusion of clotting factors

Treat the underlying cause

43
Q

What is HIT?

A

thrombocytopenia due to HMW heparin admin

44
Q

what causes HIT?

A

Heparin induced thrombocytopenia (HIT) is a clinicopathological syndrome that occurs when heparin dependent IgG antibodies bind to heparin/platelet factor 4 complexes to activate platelets and produce a hypercoagulable state.

Heparin is being recognized by our immune system and we are making antibodies that target thrombocytes and get rid of our platelets

45
Q

How long does it take for HIT to occur?

A

7-10 days after heparin administration

46
Q

Treatment for HIT?

A

Stop heparin
monitor PT PTT, INR and platelets

47
Q

What is the pathway for fibrinolysis?

A

Plasminogen → plasmin (active form) → breaks down fibrin into FSP and fibrinogen into degradation products
○ tPA activates plasminogen into plasmin (active form)
○ Urokinase and streptokinase also do this ^^

48
Q

What is TTP?

A

Thrombotic thrombocytopenic purpura
You dont have enough of the ADAMTS13 enzyme, and since insufficient, body makes blood clots.
Results in low platelets
Heparin can cause TTP

49
Q

Treatment for TTP

A

steroids, plasma exchange, immune lowering meds

50
Q

What are the 2 main regulation systems of coagulation?

A

Fibrin inhibition
Fibrinolysis

51
Q

What are the proteases made by the liver that rapidly inactivate the coagulation proteins?

A

alpha1-antiprotease
alpha2-macroglobulin
alpha2-antiplasmin
antithrombin

52
Q

After the clot is formed, how do we break it down? (fibrinolytic system)

A

plasminogen is activated into plasmin by TPA (tissue plasminogen activator)
urokinase
streptokinase+ activator=anistreplase

to break down fibrin

53
Q

what are the 2 main functions of plasmin?

A

Breaks down fibrin into split products (picked up by D-Dimer)

Breaks down fibrinogen locally.

54
Q

What can we use to keep a clot from breaking down? how does it work?

A

Aminocaproic acid
transischemic acid (TXA)

inhibits the breakdown of plasminogen to plasmin

55
Q

List the four classes of coagulation modifier drugs, how they work, and examples of each.

A

Anticoagulant-
Parenteral: heparin
Oral: Warfarin
Inhibit the action or formation of clotting factors
Prevent clot formation

Antiplatelet drugs- Aspirin
Inhibit platelet aggregation
Prevent platelet plugs

Thrombolytic drugs (Fibrinolytic)-Streptokinase
Lyse (break down) existing clots

Hemostatic or Antifibrinolytic drugs
Promote blood coagulation

56
Q

How does an indirect thrombin inhibitor work?
Examples of this type of drug?

A

Enhances antithrombin activity Inactivates factor Xa
Unfractionated heparin
LMW heparin
Fondaparinux (Arixtra)

57
Q

What is the difference in the different types of heparin?

A

How purified they are:
Unfractionated heparin
Less purified but more effective

LMW heparin
More purified but less effective

Fondaparinux (Arixtra) → pentasaccharide complex – 5 carbs stuck together
Less effective than molecular weight or unfractionated heparin

58
Q

How does a direct thrombin inhibitor work?
Examples of this type of drug?

A

they directly inhibit thrombin by binding to active sites on thrombin

Bind to both active and substrate recognition sites of thrombin:
* Hirudin (Lepirudin is recombinant form)
from leeches - saliva from leeches prevents clotting from occurring
* Bivalirudin (Angiomax)

Bind only to thrombin active sites -
* Argatroban
* Melagatran
* Dabigatran (Pradaxa)

59
Q

Explain the difference between HMW, LMW, and Fondaparinux heparins, and the use of each.

A

They all have a Pentasaccharide sequence.

Heparin: Binds and activates AT
Enhances activity (1000x)
Has a High molecular weight fractions (Unfractionated)
Extracted from porcine intestinal mucosa and bovine lung

LMW Heparin
More purified form of heparin
More specific for factor Xa
Less effect on thrombin
Less effective on coagulation in general
Examples (-parin)

Fondaparinux (Arixtra)
Synthetic
Not as effective (selective for factor X)
Less bleeding risks
Useful for HIT

60
Q

What are the toxicities and contraindications for HMW heparin?

A

Bleeding
Transient thrombocytopenia
Heparin induced thrombocytopenia (HIT)

Hemophilia
Thrombocytopenia
Severe hypertension
Intracranial hemorrhage
Infective endocarditis
Active TB
GI ulcers
Advanced hepatic disease

61
Q

What is the reversal for heparin?
How does it work?

A

protamine sulfate- made from salmon sperm now synthetic

It is highly positive so binds to the highly negatively charged heparin thereby inactivating it

62
Q

What is the normal INR?
What is the warfarin target?

A

0.8-1.2
2-3

63
Q

What is Prothrombin time?

A

The time it takes to clot

64
Q

what is the normal aPTT?

A

35-45 seconds

65
Q

List the oral anticoagulants

A

warfarin (coumadin)
Factor X inhibitors

66
Q

MOA of heparin

A

Blocks the γ-carboxylation of several glutamate residues (vitamin K dependent)
Targets 2,7,9,10

Binds and activates antithrombin

67
Q

Where was warfarin discovered and what was it initially used for?

A

Discovered by University of Wisconsin as cause for cattle hemorrhagic disease
Wisconsin Alumni Research Foundation -arin
originally meant as rat poison

68
Q

Pharmacokinetics of warfarin

A

100% oral availability
Protein binding = 99%
Long half-life = 36 hours

69
Q

What are the fibrinolytic drugs?

A

Streptokinase
urokinase
t-PA
- alteplase

70
Q

What are the targets for aspirin?

A

COX-1 Selective - platelet

TXA2 causes platelets to change shape, Granule release, and Aggregation

Inhibition of TXA2 synthesis increases bleeding time

71
Q

MOA of Clopidogrel (plavix) and ticlopidine (Ticlid)

A

Irreversibly inhibits ADP receptor on platelets causing reduction in platelet aggregation

72
Q

MOA of Abciximab

A

IIb/IIIa receptor blocker found in the common pathway
Inhibits platelet aggregation

73
Q

How can bleeding disorders be treated with Vitamin K?

A

Necessary for efficient blood coagulation
Fat soluble vitamin
Comes from:
Leafy green vegetables
Gut bacteria
Confers activity on:
Prothrombin (primarily affect this)
Factors VII, IX, and X

74
Q

How can bleeding disorders be treated with plasma fractions?

A

We can give plasma to treat bleeding disorders; replaces clotting factors. Whatever they are missing, we can isolate that factor and give to patient

75
Q

How can bleeding disorders be treated with desmopressin acetate?

A

Desmopressin Increases factor VIII activity
Good for Mild hemophilia A
Also good for von Willebrand disease

76
Q

How can bleeding disorders be treated with aminocaproic acid(fibrolytic inhibitor)

A

Competitively inhibits plasminogen activation
Stabilizes clot; prevents clot breakdown
Use
Adjunctive hemophilia therapy
Bleeding from fibrinolytic therapy
Intracranial aneurysms
Post surgical bleeding

77
Q

How can bleeding disorders be treated with Tranexamic acid (TXA)

A

Helps to stabilize clot and prevent clot breakdown→helps blood to clot to stop bleeding
Decreased risk of death in major bleeding
Used for: Trauma, heavy menstrual bleeding, postpartum, epistaxis
So used for more massive bleeds
MOA
Antifibrinolytic
Inhibits plasminogen->plasmin

Pharm Test 4 (9 decks)

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