Anti-plt

Question 1

The majority of receptors are:

Answer 1

seven-transmembrane G protein–coupled receptors (GPCRs)

Question 2

GPCRs for...
ADP:
thrombin:
thromboxane:
serotonin:
epinephrine:

Answer 2

P2Y1, P2Y12
PAR1, PAR4
 TP
5-HT2A
β2-adrenergic

Integrin receptors are linked to cytoskeletal elements and recognize collagen (α2β1) and fibrinogen (αIIbβ3, also known as the GPIIb/IIIa receptor). GPVI is also activated by collagen. The GPIb/IX/V complex, which binds vWF, P selectin, and collagen, is a member of the leucine-rich receptor class. The full host of platelet surface receptors and their actions has been reviewed recently.5

Question 3

Integrin receptors are linked to:
and recognize:

GPVI is also activated by:

GP Ib/IX/V complex, which binds:

Answer 3

cytoskeletal elements
collagen (α2β1) and fibrinogen (αIIbβ3)

collagen

vWF, P selectin, and collagen
is a member of the leucine-rich receptor class

Question 4

drugs
P2Y1, P2Y12 - ADP:
PAR1, PAR4 - thrombin:
TP TXA2 thromboxane:
5-HT2A - serotonin:
β2-adrenergic - E:

Answer 4

clopridogrel

NSAID, aspirin AA inside cell via COX1 inhibition

Question 5

ADP receptors
ADP is released from:
helps to amplify the platelet aggregation response.

Interaction of ADP with both receptors is necessary for:

Agonism at the P2Y1 receptor is associated with:

P2Y12 receptor is associated with

Answer 5

α-granules

both receptors is necessary for full ADP-induced platelet aggregation, but each receptor contributes slightly different platelet effects

platelet shape change and mild, reversible aggregation

integrin activation and platelet granule secretion

Question 6

thienopyridines are a class of drugs:
MoA

binding:
names:

prodrug ..

Answer 6

interfere with ADP-induced platelet aggregation
platelet P2Y12 receptor
irreversible
clopidogrel (Plavix)
ticlopidine (Ticlid, discontinued in the United States) prasugrel (Effient)
biotransformation via hepatic P-450 enzymes

Question 7

Clopidogrel
Dosages of 18.75 mg per cat PO q24h decreased ADP- and collagen-induced platelet aggregation and platelet serotonin release (an indicator of:

meaning..

Answer 7

dense granule secretion

Clopidogrel is thus effective in decreasing the release of the procoagulant molecules from platelet granules and so may slow in vivo thrombus growth by delaying additional platelet activation

Question 8

Nucleoside analogs
inhibit the effects of:
via:
binding:

names:

MoA:

Answer 8

ADP on platelet aggregation
unlike the thienopyridines, these drugs do not require hepatic metabolism for effect and result in a
reversible inhibition of the P2Y12 receptor

cangrelor
ticagrelor

Ticangrelor is designed for oral
cangrelor is administered intravenously. Both drugs

noncompetitively inhibit ADP binding to the P2Y12 receptor through a specific binding site
nucleoside analogs provide rapid, reversible platelet inhibition, platelet activity returns to normal 12 hours

Question 9

Cyclooxygenase Inhibitors
TXA2 is a potent _____ & _____:

produced via a cyclooxygenase (COX) enzyme in the platelet cytosol. Arachidonic acid from the platelet membrane is used to produce:

platelets are thought to contain only the ___ isoform:

TXA2 plays an important role in:
drugs that block COX:

Answer 9

vasoconstrictor and platelet agonist

TXA2

COX-1 isoform

recruitment and activation
aggregation

Question 10

archetypical COX inhibitor is:
____ blockade of platelet COX-1:
platelets cannot manufacture additional copies of COX (they lack a cell nucleus), and so blockade by ASA is:

explain the reason for the success of “ultralow-dose”:

Answer 10

acetylsalicylic acid (ASA, aspirin)
irreversible 

permanent for the life of the platelet 6-7day

irreversible/permanent inhibition of COX-1 = lifespan

Question 11

other NSAIDs cause ____ blockade of platelet COX:

and isoform COX:

Answer 11

reversible - do not result in such profound decreases in platelet activity

platelet COX is thought to be primarily COX-1, drugs with a high degree of specificity for the COX-2 isoform (e.g., the coxibs) are thought to have minimal to no effect on platelet reactivity

Question 12

COX activity of platelets can be assayed by using:

“aspirin resistance”

Answer 12

arachidonic acid alone as an aggregating agent
or TXA2

populations of dogs whose platelets do not show aggregation responses when exposed to arachidonic acid or TXA2

insensitive to the platelet effects of ASA or other NSAIDs

Question 13

Cats in general have reactive platelets .:. asprin:

Answer 13

sensitivity of platelets to other agonists that minimize the contribution of TXA2

Question 14

Fibrinogen Receptor Antagonists
Fibrinogen receptor antagonists are focused on the:

final common pathway=

names:

Answer 14

final common pathway of platelet activation
expression of an active GPIIb/IIIa fibrinogen receptor

< platelet response to agonists is minimized because all activated platelets are inhibited from contributing to clot formation

Abciximab (ReoPro)
eptifibatide (Integrilin)
tirofiban (Aggrastat)
IV formulations only

Question 15

Abciximab MoA:

Eptifibatide and tirofiban MoA:

Answer 15

Fab-fragment - noncompetitive inhibitor of GPIIb/IIIa

smaller compounds that competitively block the fibrinogen binding site of GPIIb/IIIa and are more specific for this receptor than abciximab

recovery of platelet function occurs within 4 hours of cessation of infusion of these drugs

Question 16

dogs, the in vitro addition of abciximab to whole blood prolonged PFA-100 closure time but did not affect:

Answer 16

thromboelastography variables