SACCM 164: Antiplatelet drugs Flashcards
Where is vWF stored?
in the Weibel-Palade bodies in the endothelium
in the alpha granules in platelets
What clotting factor initiates “tathering” of platelets?
vWF
What platelet receptor does vWF bind to?
Factor GP Ib-IX-V
Why are platelets and vWF more prominent in arterial thrombi?
because shear stress exposes the platelet binding site on vWF -> increaes vWF affinity to platelet GP Ib-IX-V
What platelet receptor does collagen bind to?
GP VI
What are the 2 names for the platelet receptor fibrinogen will bind to?
- integrin alpha IIb beta 3
- GP IIb/IIIa
What 3 changes do platelets undergo after being activated?
- shape change from discoid to ameboid shape with filopodia
- release of alpha and dense granule content
- cell membrane structural change –> phospholipid structure change
what complexes require the structural cell membrane change of activated platelets?
tenase and prothrombinase complexes need phospholids
what are the parts of the tenase complex?
- FIXa
- FVIIIa
- Ca2+
- Phospholipids
What are the parts of the prothrombinase compllex?
- FXa
- FVa
- Ca2+
- phospholipids
Name the 7 different molecule types present in the alpha granules of platelets
- adhesion molecules
- chemokines
- coagulation factors
- growth and angiogenic factors
- immunologic molecules
- other proteins
Name the 4 different molecule types present in the dense granules of platelets
- Ions
- Nucleotides
- Membrane proteins
- Transmitters
Name 6 different molecules stored in the alpha granules of platelets
- vWF
- fibrinogen
- FV
- FVIII
- plasminogen
- PAI-1
- IgG
- Albumin
Name 6 different molecules stored in the dense granules of platelets
- Ca
- ADP
- ATP
- serotonine
- epinephrine
- histamine
What platelet receptors does ADP work on?
P2Y1
P2Y12
What platelet receptors does thrombin work on?
PAR-1
PAR-4
What platelet receptor does TXA2 work on?
TP receptor
What platelet receptor does serotonine work on?
5-HT2A
What platelet receptor does epinephrine work on?
beta-2 receptors
Name 6 different substances that can activate platelets
- vWF
- ADP
- TXA2
- thrombin
- serotonin
- epinephrine
- collagen
What receptor does clopidogrel inhibit?
P2Y12 receptor on platelets
What is the different effect of P2Y1 versus P2Y12 receptor activation to platelets?
P2Y1 –> shape change and mild aggregation
P2Y12 –> integrin activation (GPIIb/IIIa!), granule content release, plays role in TXA2 production
What breed has been shown to carry a P2Y12 mutation?
Greater Swiss Mountain Dog
Name 2 other drugs than Clopidogrel from the family of Thienopyridines
- Ticlopride
- Prasugrel
What family of drugs does Clopidogrel belong to?
Thienopyridines
What could alter the efficacy of clopidogrel or make its efficacy unpredictable?
- administration of other drugs needing cytochrome P450 pathway
- liver disease/concurrent comorbidities
- genetic cytochrome P450 pathway alterations
What other effect on hemostasis than platelet activation does TXA2 have?
vasoconstriction
How long does the platelelt inhibition of aspirin last?
6 days (life-span of platelet, cannot produce more COX-1 due to lack of nuclues)
What is the proposed reason for some dogs or cats not responding to aspirin with platelet inhibition?
subset of dogs with platelets not responding to TXA2
cats have hyperactive platelets –> can use other patways sufficiently enough
What type of drugs are Abciximab, Aptifibatide, and Tirofiban?
Platelet fibrinogen Receptor Antagonists
–> antagonize GPIIb/IIIa receptors
