SACCM 164: Antiplatelet drugs Flashcards

1
Q

Where is vWF stored?

A

in the Weibel-Palade bodies in the endothelium
in the alpha granules in platelets

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2
Q

What clotting factor initiates “tathering” of platelets?

A

vWF

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3
Q

What platelet receptor does vWF bind to?

A

Factor GP Ib-IX-V

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4
Q

Why are platelets and vWF more prominent in arterial thrombi?

A

because shear stress exposes the platelet binding site on vWF -> increaes vWF affinity to platelet GP Ib-IX-V

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5
Q

What platelet receptor does collagen bind to?

A

GP VI

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6
Q

What are the 2 names for the platelet receptor fibrinogen will bind to?

A
  • integrin alpha IIb beta 3
  • GP IIb/IIIa
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7
Q

What 3 changes do platelets undergo after being activated?

A
  • shape change from discoid to ameboid shape with filopodia
  • release of alpha and dense granule content
  • cell membrane structural change –> phospholipid structure change
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8
Q

what complexes require the structural cell membrane change of activated platelets?

A

tenase and prothrombinase complexes need phospholids

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9
Q

what are the parts of the tenase complex?

A
  • FIXa
  • FVIIIa
  • Ca2+
  • Phospholipids
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10
Q

What are the parts of the prothrombinase compllex?

A
  • FXa
  • FVa
  • Ca2+
  • phospholipids
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11
Q

Name the 7 different molecule types present in the alpha granules of platelets

A
  • adhesion molecules
  • chemokines
  • coagulation factors
  • growth and angiogenic factors
  • immunologic molecules
  • other proteins
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12
Q

Name the 4 different molecule types present in the dense granules of platelets

A
  • Ions
  • Nucleotides
  • Membrane proteins
  • Transmitters
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13
Q

Name 6 different molecules stored in the alpha granules of platelets

A
  • vWF
  • fibrinogen
  • FV
  • FVIII
  • plasminogen
  • PAI-1
  • IgG
  • Albumin
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14
Q

Name 6 different molecules stored in the dense granules of platelets

A
  • Ca
  • ADP
  • ATP
  • serotonine
  • epinephrine
  • histamine
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15
Q

What platelet receptors does ADP work on?

A

P2Y1
P2Y12

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16
Q

What platelet receptors does thrombin work on?

A

PAR-1
PAR-4

17
Q

What platelet receptor does TXA2 work on?

A

TP receptor

18
Q

What platelet receptor does serotonine work on?

A

5-HT2A

19
Q

What platelet receptor does epinephrine work on?

A

beta-2 receptors

20
Q

Name 6 different substances that can activate platelets

A
  • vWF
  • ADP
  • TXA2
  • thrombin
  • serotonin
  • epinephrine
  • collagen
21
Q

What receptor does clopidogrel inhibit?

A

P2Y12 receptor on platelets

22
Q

What is the different effect of P2Y1 versus P2Y12 receptor activation to platelets?

A

P2Y1 –> shape change and mild aggregation
P2Y12 –> integrin activation (GPIIb/IIIa!), granule content release, plays role in TXA2 production

23
Q

What breed has been shown to carry a P2Y12 mutation?

A

Greater Swiss Mountain Dog

24
Q

Name 2 other drugs than Clopidogrel from the family of Thienopyridines

A
  • Ticlopride
  • Prasugrel
25
Q

What family of drugs does Clopidogrel belong to?

A

Thienopyridines

26
Q

What could alter the efficacy of clopidogrel or make its efficacy unpredictable?

A
  • administration of other drugs needing cytochrome P450 pathway
  • liver disease/concurrent comorbidities
  • genetic cytochrome P450 pathway alterations
27
Q

What other effect on hemostasis than platelet activation does TXA2 have?

A

vasoconstriction

28
Q

How long does the platelelt inhibition of aspirin last?

A

6 days (life-span of platelet, cannot produce more COX-1 due to lack of nuclues)

29
Q

What is the proposed reason for some dogs or cats not responding to aspirin with platelet inhibition?

A

subset of dogs with platelets not responding to TXA2
cats have hyperactive platelets –> can use other patways sufficiently enough

30
Q

What type of drugs are Abciximab, Aptifibatide, and Tirofiban?

A

Platelet fibrinogen Receptor Antagonists
–> antagonize GPIIb/IIIa receptors