Lecture 7 Antiplatelets Flashcards
what occurs first following endothelial damage?
transient vasoconstriction via neural stimulation reflex and endothelin released from damaged cell
platelets bind to exposed collagen via _____ binding the ____ receptor
VWF;
Gp1B
After binding VWF, platelets are actiavted and release what three substances ?
ADP, TXA2, 5HT
and Ca
binding of ADP induces ____ expression at the platelet surface, which binds _____
Gp2b/3a; fibrinogen
intact endothelial cells release ____ and ____ to increase blood flow and inhibit platelet aggregation
PGI2, NO
what enzyme is responsible for synthesis of TXA2?
COX 1
Aspirin (ASA)’s mechanism of action:
irreversibly inhibits COX1 and COX2 via acetylation
at low doses, ASA preferentially inhibits ____, causing _____. at high doses, it inhibits ____.
COX 1, decreased TXA2 synth;
COX 2
ASA’s effect on bleeding time? PT? aPTT?
increased bleeding time, no effect on PT or PTT
side effects of ASA: ____ due to inhibition of COX 1,
gastric bleeding
What is the name of the 2 types of ADP receptors? What general receptor class do they belong to?
P2Y1, P2Y12;
GPCR
what is another name of the ADP receptor inhibitor class?
thienopyridines
name the 4 ADP receptor inhibitors listed in FA
clopidrogel, ticlodipine, ticagrelor, prasugrel
Prausgrel vs ticagrelor:
which is a pro-drug?
which binds irreversibly?
which binds to an allosteric site?
prasugrel,
prasugrel,
ticagrelor
_____ may induce TTP by inducing antibodies against what protease?
ticlodipine, ADAMTS13
what does ADAMTS13 usually do
cleaves circulating vWF
ADP receptor inhibitors are generally used for ______ and _____
acute coronary syndromes, coronary stenting
what is the newest drug mentioned in the notes that inhibits ADP receptors?
cangrelor
name the 3 GP2b/3a receptor inhibitors
abciximab, tirofiban, eptifibatide
which of the Gp2b3a inhibitors….
is a chimeric monoclonal Ab?
is administered IV due to short half life?
abciximab,
tirofiban and eptifibatide
what are the two phosphodiesterase inhibitors?
dipyridamole, cilostazol
PDE inhibitor mechanism:
increased cAMP opposes ____ signalling, causing decreased platelet aggregation. in addition, they cause general ____
P2Y12;
vasodilation
the PDE inhibitors are used for intermittent ____, coronary _____, and angina prophylaxis
claudication;
vasodilation
Vorapaxar and atopaxar are ______. they cause decresed release of ____ and prevent thrombin from activating platelets
protease activated receptor (PAR) inhibitors;
Ca
vorapaxar and atopaxar inhibit PARs by what?
proteolytic cleavage
what kind of half life does vorapaxar have? what is it used with to prevent thrombosis in patients with previous MI?
long (ie 3 to 4 days);
used with aspirin or clopidogrel
