Brainscape's Knowledge GenomeTM

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


See full index

Cardiovascular: pharmacology > Antiplatelet, anticoagulant and thrombolytic drugs and the mechanism of clotting > Flashcards

Antiplatelet, anticoagulant and thrombolytic drugs and the mechanism of clotting Flashcards

1
Q

What is the starting process in almost all clot formations?

A

It begins with a local event that causes damage to the wall

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

What does the damage to the endothelial wall expose?

A

Tissue factor and collagen

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

What does the exposed collagen bind to?

A

vWF

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

What does collagen bound vWF act as ?

A

a cross bridge because it will also allow the platelets to bind to it through the glycoprotein Ib (GP Ib) receptor on the platelet surface.

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

What is the receptor on the platelet that binds to vWF – collagen complex?

A

Glycoprotein Ib

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

How is the binding of the platelet to the blood vessel further stabalised ?

A

Interactions are formed by Integrin A2 B1 and glycoprotein VI on the platelet binding to collagen

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

Which two things initiate platelet activation?

A

Glycoprotein VI anchoring and thrombin

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

What does the platelet do in response to activation?

A

a. 1.changes shape (extends pseudopodia) which then gives aggregated platelets
b. 2.The platelet also starts to synthesise thromboxane A2 (TA2,)

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

How is TA2 formed?

A

It is formed from arachidonic acid through the enzyme COX1

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

TA2 acts in both an —– and ____ manner.

A

TA2 acts in both an autocrine and paracrine manner.

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

what is the receptor called that TA2 binds to?

A

GPCRTXA2

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

what does the binding of TA2 to GPCR TXA2 do?

A

causes the release of

i) 5-hydroxytryptamine (aka seratonin) and ADP
ii) vWF and factor V

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

what do the dense granules release?

A

5- hydroxytryptamine (5-HT) (aka seratonin) and ADP

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

what do the alpha granules release?

A

vWF and factor V

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

why do the blood vessels vasoconstrict?

A

because TXA2 acts directly on smooth muscle and also 5-HT binds to receptors on the surface causing vasoconstriction

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

what does ADP bind to ?

A

platelet GPCR P2Y12 receptors

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

what does the binding of ADP do? 3 things

A

i) activation of further platelets
ii) Increases the expression of glycoprotein IIb and IIIa receptors
iii) causes exposure of acidic phospholipids on the platelet surface - this facilitates the formation of the clot

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

what do GP IIb and IIIa do?

A

they are binding points for fibrinogen on the platelet surface

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

what is the KEY event in the coagulation cascade?

A

the production of protease thrombin (factor IIa) that cleaves fibrinogen to fibrin to form a solid clot

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

what is coagulation?

A

the conversion of the soft plug to form a solid clot which assists in the healing process.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q
  1. what does the tissue injury expose ?
A

matrix tissue factor (thromboplastin)

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

2.which factor binds to TF?

A

VII - this complex TF:VIIa is now active

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

3.what does the TF:VIIa complex do?

A

activates factor X (x- Xa)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q
  1. what does the activates Xa bind to ?
A

Va

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q
  1. what does the Complex VaXa do?
A

converts prothrombin to thrombin - this is the key player

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q
  1. what is the first thing that thrombin does?
A

activates further platelets - in doing so it causes the release of factor V from alpha granules in the platelet cytoplasm - when these factors reach the surface they become active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q
  1. what does thrombin do to TF:VII (8) ?
A

It liberates factor VIII which then becomes active

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

8.what does thrombin do to XI?

A

converts it to XIa

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

9.how is IX activated?

A

by wither TF- VIIa or XIa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q
  1. what does IXa do?
A

binds with VIIIa to convert X to Xa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q
  1. what dies the Xa form a complex with in order to bind prothrombinase?
A

Va

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

12.what does the Xa and Va complex do?

A

convert II to IIa

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

13.what does thrombin do?

A

cleaves fibrinogen, forming fragments that spontaneously to form fibrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q
  1. Which factor then cross links the polymer to form a fibrin fibre network and a solid clot ?
A

VIIIa

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

what are the main components of arterial thrombus?

A

white thrombus: mainly platelets in a fibrin mesh and relatively few RBCs

36
Q

where do arterial thrombus normally do to cause problems ?

A

they embolise and if this happens in the carotid arteries , then can get a stroke

37
Q

what are arterial thrombus normally treated using?

A

antiplatelets

38
Q

what are the main components of venous thrombus?

A

white head, jelly like tail and fibrin rich red thrombus

39
Q

what normally happens to venous thrombi?

A

if detaches forms an embolus that usually lodges in the lung (pulmonary embolism)
also can get DVT

40
Q

what are venous thrombi treated with?

A

anticoagulants

41
Q

which clotting factors require post-translational modification for subsequent function of the active factors?

A

II,VII,IX,X

42
Q

VIIa, IXa, Xa that act as ____- proteases

A

VIIa, IXa, Xa that act as serine proteases

43
Q

what is the specific reaction happening in post-translaitonal modification?

A

carboxylation of glutamate residues

44
Q

factor II goes from being _______ to ______ with vitamin K modification. It is still inactive though

A

factor II goes from being descarboxythrombin to prothrombin with vitamin K modification. It is still inactive though

45
Q

The carboxylase enzyme that mediates ______ ________ requires vitamin __ in its _____ form as an essential _____

A

The carboxylase enzyme that mediates gamma carboxylation requires vitamin K in its reduced form as an essential cofactor

46
Q

what is the oxidised form of vitamin K called?

A

epoxide

47
Q

what is the reduced form of vitamin K called?

A

hydroquinone

48
Q

what is the enzyme that converts vitamin K from oxidised to reduced?

A

vitamin K reductase

49
Q

what is the role of warfarin?

A

blocks vitamin K reductase so get get a reduced Gamma carboxylation of 2,7,9,10 and this interrupts the coagulation cascade

50
Q

what are anticoagulants used for ? 4 things?

A
  • deep vein thrombosis (DVT)
  • prevention of post-operative thrombosis
  • patients with artificial heart valves
  • atrial fibrillation
51
Q

what risks do anticoagulants carry?

A

haemorrhage

52
Q

warfarin Blocks coagulation in ____, not in ___

A

Blocks coagulation in vivo, not in vitro

53
Q

what is the downside of warfarin?

A

it has a low therapeutic ratio

54
Q

what has to be checked regularly with warfarin?

A

INR

55
Q

name 3 ways to potentiate warfarin action?

A
  • liver disease – decreased clotting factors
  • high metabolic rate – increased clearance of clotting factors
  • drug interactions
56
Q

name 3 ways to lessen warfarin action?

A

Physiological state – pregnancy (increased clotting factor synthesis) – hypothyroidism - reduce metabolism (decreased degradation of clotting factors)

  • Vitamin K consumption
  • drug interactions
57
Q

how is warfarin overdose treated?

A

vitamin K administration or concentrate of plasma clotting factors

58
Q

name the important inhibitor of coagulation in the body

A

antithrombin III

59
Q

what is the action of AT III

A

it neutralises all serine protease factors by binding to their active sites in a 1 to 1 ratio

60
Q

what is the action of heparin?

A

it binds to ATIII increasing its affinity for serine protease clotting factors to greatly increase their rat of inactivation

61
Q

what clotting factors is heparin particularly aimed at?

A

Xa and IIa (thrombin)

62
Q

what must heparin bind to to inhibit IIa?

A

both IIa and AT III

63
Q

what must heparin bind to to inhibit Xa?

A

only AT III

64
Q

give 2 examples of LMWH?

A

enoxaparin and dalteparin

65
Q

when is heparin preferred to LMWH?

A

in renal failure because heparin is eliminated by routes other than the kidneys

66
Q

which factor do LMWH and fondaparinux inhibit?

A

Xa

67
Q

give 4 side effects of heparin and LMWH

A
  1. haemorrhage
  2. osteoporosis
  3. hypoaldosteronism
  4. hypersensitivity reactions
68
Q

what substance inactivates heparin and is used in haemorrage?

A

protamine sulfate

69
Q

name a new orally active agent that is a direct inhibitor of thrombin

A

dabigatran etexilate

70
Q

name a new orally active agent that is a direct inhibitor of Xa

A

rivaroxiban

71
Q

what are the advantages of the new orally active anticoagulant agents? 2

A

convenience of administration

predictable degree of anticoagulation, but no specific agent available to reduce haemorrhage in overdose

72
Q

what are dabigatran etexilate and rivaroxiban used in?

A

to prevent venous thrombosis in patients undergoing hip and knee replacements

73
Q

how does aspirin work on platelets?

A

it irreversibly blocks COX in platelets preventing TXA2 synthesis

74
Q

how does aspirin work on endothelial cells

A

blocks COX inhibiting the production of antithrombotic prostaglandin I2

75
Q

what is aspirin mainly used for?

A

thromboprophylaxis in pateints at high cardiovascular risk

76
Q

what are the main side effects of aspirin?

A

gastrointestinal bleeding and ulceration

77
Q

how does clopidogrel work?

A

links to the P2Y12 receptor by a disuphide bond producing irreverible inhibition

78
Q

when is it used?

A

in patients intolerant to aspirin and alongside aspirin

79
Q

how does tirofiban work?

A

blocks GPIIb IIIa receptor - preventing fibrin linking

80
Q

what does plasmin do?

A

breaks fibrin into fibrin fragments to get clot lysis

81
Q

what is the plasmin precursor?

A

plasminogen

82
Q

what is the enzyme required to form plasmin

A

endogenous tissue plasminogen activator (tPA)

83
Q

name three drugs that activate plasminogen

A

streptokinase, alteplase and duteplase

84
Q

what is the role of fibrinolytics?

A

they are usedto reopen occluded arteries in acute MI or stroke

85
Q

what is a side effect of streptokinase?

A

allergic reactions - should not be given to patients with recent streptococcal infections

86
Q

alteplase and duteplase and more effective on ___ bound plasminogen than____ plasminogen

A

alteplase and duteplase and more effective on fibrin bound plasminogen than plasma plasminogen

87
Q

what is used if there is a haemorrhage with fibrinolytics?

A

tranexamic acid which inhibits plasminogen activation

Cardiovascular: pharmacology (6 decks)

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