Exam 4 - Antiplatelets Hockerman Flashcards
arrest of bleeding from a damaged blood vessel
a. hemostasis
b. coagulation
a. hemostasis
multi-step process to “plug” the leaking vessel
a. hemostasis
b. coagulation
b. coagulation
true or false: platelets have organelles and secretory granules, but no nucleus
true
3 steps of platelet activation
-platelet adhesion and shape change
-platelet secretion
-platelet aggregation
platelet adhesion is mediated by:
-_____ binding to collagen
-_____ binding to von Willebrand Factor bridged to collagen
-shape change facilitates receptor binding
GP Ia (glycoprotein Ia)
GP Ib (glycoprotein Ib)
intact endothelial cells secrete _____ (aka prostacyclin) to inhibit thrombogenesis
PGI2
platelet secretion: platelet granules release what 3 things?
-ADP
-thromboxane A2 (TXA2)
-serotonin (5-HT)
platelet aggregation: ADP, 5-HT, and TXA2 activation induces conformation of GPIIb/IIIa receptors to bind __________
fibrinogen
platelet are cross-linked by
a. plasminogen
b. fibrinogen
c. TXA2
d. ADP
b. fibrinogen
aspirin is a _____ inhibitor
a. COX-1
b. ADP receptor
c. GP11b/IIIa receptor
d. PDE-3
e. protease-activated receptor
a. COX-1
inhibition of _____ synthesis in platelets is the key to anti-platelet activity of ASA
TXA2 (thromboxane)
true or false: aspirin reduces bleeding time
false (prolongs it)
aspirin indication
prophylaxis and treatment of arterial thromboembolic disorders
after taking aspirin, hemostasis returns to normal ___ hours after last dose
36
aspirin can cause upper GI bleeding, due to inhibition of _____ mediated prostaglandins
a. COX1
b. COX2
a. COX1
acute aspirin overdose can be induced by doses above _____ mg/kg
a. 50
b. 150
c. 250
d. 500
b. 150
(doses above 500 mg/kg can be fatal)
_____ produces prostacyclin in endothelial cells -> leads to vasodilation and inhibition of platelet aggregation
a. COX-1
b. COX-2
c. TXA2
b. COX-2
_____ produces TXA2 in the platelets -> which leads to vasoconstriction and platelet aggregation
a. COX-1
b. COX-2
a. COX-1
selective _____ inhibitors block synthesis of prostacyclin while not preventing synthesis of TXA2 -> leads to CV risk
a. COX-1
b. COX-2
c. 5-HT
b. COX-2
what two ADP receptors are involved in activating platelets?
P2Y1
P2Y12
P2Y1 is coupled to which GPCR?
a. Gi
b. Gs
c. Gq
c. Gq
P2Y12 is coupled to which G protein?
a. Gi
b. Gs
c. Gq
a. Gi
activation of which ADP receptor is required for platelet activation by ADP?
a. P2Y1
b. P2Y12
c. both
c. both
ticlopidine (Ticlid) and clopidogrel (Plavix) are both prodrugs that irreversibly block ___ receptor on platelet and subsequent activation of __________ complex
ADP; GPIIb/IIIa
how long does the action of ticlopidine and clopidogrel last?
several days after last dose
which has a lower toxicity profile?
a. Ticlopidine (Ticlid)
b. Clopidogrel (Plavix)
b. Clopidogrel (Plavix)
ADP receptor inhibitors uses (5 of them)
-acute coronary syndrome
-recent MI
-stroke
-established peripheral vascular disease
-stent procedures
which drug may induce thrombotic thrombocytopenia purpura (TTP)?
a. clopidogrel
b. ticlopidine
c. prasugrel
d. ticagrelor
b. ticlopidine
prasugrel (Effient) and ticagrelor (Brilinta) is approved for treatment of _____ _____ _____, and _____ _____ _____
acute coronary syndrome; percutaneous coronary intervention (PCI)
prasugrel is a prodrug that requires _____ + CYP___/___ to generate active metabolite
esterases
CYP3A4/2B6
does prasugrel bind irreversibly or reversibly?
irreversibly
(long duration of action; it is a prodrug)
prasugrel and ticagrelor are NOT recommended before what procedure?
CABG
ticagrelor has __________ binding
a. irrev
b. reversible
b. reversible
(binds to an allosteric site)
Cangrelor (Kangreal) has a fast onset of action. What is the half-life range?
3-5 min
(it is given IV)
true or false: cangrelor (Kangreal) requires bioactivation by metabolic enzymes
false
route of administration for cangrelor (Kangreal)
IV
cangrelor (Kangreal) is used as an adjunct to _____
PCI
SELECT ALL THAT APPLY: which of these do not require bioactivation by metabolic enzymes?
a. clopidogrel
b. prasugrel
c. ticagrelor
d. cangrelor
c. ticagrelor
d. cangrelor
what structural feature makes clopidogrel and prasugrel irreversibly bind to the P2Y12 ADP receptor?
they have thiol groups which make disulfide crosslinks, which makes it irreversible
what class of drug’s mechanism is to inhibit fibrinogen crosslinking of platelets?
a. ADP receptor inhibitors
b. COX inhibitors
c. GP IIb/IIIa receptor inhibitors
d. PDE-3 inhibitors
c. GP IIb/IIIa receptor inhibitors
A chimeric mouse-human monoclonal antibody directed against the human GPIIb-IIIa
a. abciximab
b. eptifibatide
c. tirofiban
a. abciximab
A synthetic peptide which selectively blocks GPIIb-IIIa in a reversible manner
a. abciximab
b. eptifibatide
c. tirofiban
b. eptifibatide
A nonpeptide tyrosine analogue which is specific for the GPIIb-IIIa and inhibits fibrinogen binding
a. abciximab
b. eptifibatide
c. tirofiban
c. tirofiban
true or false: eptifibatide binds reversibly to block GPIIb-IIIa receptor
true
eptifibatide duration of action (range)
6-12 hours
eptifibatide use
a. combined with heparin to treat acute coronary syndrome
b. prevent thromboembolism in unstable angina and angioplastic coronary procedures
c. prevent thromboembolism in coronary angioplasty
b. prevent thromboembolism in unstable angina and angioplastic coronary procedures
eptifibatide has what three amino acids as part of its structure?
arg (R), gly (G), asp (D)
where is eptifibatide derived from?
rattlesnake venom
which does not reversibly bind to the GP IIb/IIIa receptor?
a. abciximab
b. eptifibatide
c. tirofiban
a. abciximab
which is combined with heparin to treat acute coronary syndrome?
a. abciximab
b. eptifibatide
c. tirofiban
c. tirofiban
abciximab use
a. prevent thromboembolism in coronary angioplasty
b. to prevent thromboembolism in unstable angina and angioplastic coronary procedures
c. combined with heparin to treat acute coronary syndrome
a. prevent thromboembolism in coronary angioplasty
which is combined with t-PA for early treatment of acute MI?
a. abciximab
b. eptifibatide
c. tirofiban
a. abciximab
how many hours does it take for platelet function to come back with abciximab?
48 hours
abciximab binds to GP IIb/IIIa to inhibit __________ __________
platelet aggregation
PDE-3 inhibitor drugs (2 of them)
dipyridamole (Persantine)
cilostazol (Pletal)
(dipyridamole mainly inhibits PDE5, but also PDE3 to lesser extent)
which drug, when combined with warfarin, can prevent embolization from prosthetic heart valves?
a. dipyridamole (Persantine)
b. cilostazol (Pletal)
a. dipyridamole (Persantine)
which drug, when combined with ASA, can prevent cerebrovascular ischemia?
a. dipyridamole (Persantine)
b. cilostazol (Pletal)
a. dipyridamole (Persantine)
which PDE-3 inhibitor is used for intermittent claudication?
a. dipyridamole (Persantine)
b. cilostazol (Pletal)
d. cilostazol (Pletal)
(intermittent claudication is muscle pain when exercising; usually in legs bc of reduced blood flow due to atherosclerosis)
thrombin activates __________ at nanomolar concentrations. It does this via proteolytic cleavage of PAR-1 receptors on __________ surface (same word in each blank)
platelets
PARs (protease activated receptors) are _____ coupled to release of ___ from stores
GPCRs; Ca2+
PAR (protease activated receptor) inhibitor drug
vorapaxar
is vorapaxar (Zontivity) reversible or irreversible?
reversible
(it competitively inhibits PAR-1 receptor)
how does vorapaxar (Zontivity) work?
inhibits thrombin interaction with PAR, thereby inhibiting thrombin activation of platelet aggregation
what is vorapaxar (Zontivity) used for?
prophylactic to prevent thrombosis in pts with previous MI or PAD
vorapaxar is used with _____ or _____
aspirin or clopidogrel
contraindications for vorapaxar (3 of them)
history of stroke, TIAs, or intracranial hemorrhage
half-life of vorapaxar (Zontivity) (range)
3-4 days
(very long; antiplatelet effect lasts days after discontinuation)
common indication for cilostazol
PAD
(intermittent claudication is a typical symptom of PAD)
