3.B-Antiplatelets Flashcards
What can arterial thrombosis cause?
ischemic necrosis of tissue supplied by the artery
What does arterial thrombosis often result in?
MI
stroke
limb gangrene
What is the appearance of a desired artery?
open
no blockage of blood flow
sheet of endothelial cells
What can enter the sub endothelial space of an artery if that artery has been damaged by hypertension?
LDL
Where do atherosclerotic plaques form?
arteries
What causes atherosclerosis?
infiltration of the sub-endothelial space by LDL
What can happen if an atherosclerotic plaque ruptures?
ischemia or infarction
What are platelets?
circulating cells that aggregate on damaged blood vessel walls
What do you we mean when we say that a ruptured atherosclerotic plaque “fools” platelets?
the rupture makes platelets think there is damage to the vessel wall, resulting in the aggregation of platelets on the wall and blocking blood flow
What is ischemia?
inadequate blood supply to a tissue
What is infarction? Give an example.
a complete version of ischemia, cell death results
ex: myocardial infarction (heart attack)
-death of cardiac muscle as a result of insufficient blood flow
What are the three possible consequences of ischemia? List the artery being affected.
myocardial infarction (heart attack)
-occurs in coronary artery (coronary artery disease)
cerebrovascular accident (stroke)
-occurs in cerebral arteries
peripheral arterial disease
-occurs in arteries of limbs
What are some characteristics of platelets?
fragments of larger multinucleated cells
no nucleus
contain granules in cytoplasm
contain COX-1
What are the three jobs of platelets?
adhere to damaged vessel walls
aggregate to form a platelet plug
activate coagulation cascade & other platelets
How do platelets adhere to injured areas?
activation of glycoprotein Ib receptors
-constitutively expressed on platelet surface
-affinity for collagen and vWF
What are the mechanisms for platelet activation?
exposure to subendothelial surfaces
exposure to chemical activators
Which receptors emerge once a platelet has become activated?
glycoprotein IIb/IIIa
What is the job of the GP IIb/IIIa receptor?
promote platelet aggregation
What is the main target of the GP IIb/IIIa receptor?
fibrinogen
What is the role of fibrinogen?
precursor of fibrin
links platelets to ensure aggregation
localizes substrates for clot formation
Which granules do activated platelets release? What happens after they are released?
ADP and TXA2
activation of resting platelets and initiates coagulation cascade
What is the precursor of prostacyclin? Which cells produce prostacyclin?
arachidonic acid
endothelial cells
What does prostacyclin promote?
vasodilation
decreases platelet aggregation
What are the products of cyclooxygenase in arteries?
arachidonic acid is the precursor to both
COX-1 –> thromboxane A2
COX-2 –> prostacyclin
Which enzyme does ASA inhibit?
COX-1 and COX-2
50-100x more potent for COX-1 at 81mg
What type of inhibitor is ASA?
irreversible inhibitor
-platelets cannot regenerate COX
-allows OD dosing
What are the ADP receptor antagonists?
clopidogrel
prasugrel
ticagrelor
True or false: clopidogrel is a prodrug that requires activation in the liver by CYP 2C19
true
What does clopidogrel do?
inhibits ADP receptor
*remember that ADP can activate platelets
What kind of inhibitor is clopidogrel?
irreversible inhibitor
What does prasugrel do?
ADP receptor antagonist
True or false: prasugrel is a prodrug but it has way more intra-subject variability compared to clopidogrel
false
yes its a prodrug but there is less variability than clopidogrel
With prasugrel there is concern for serious bleeding in some patients, what are the risk factors?
older than 75
less than 60kg
What is different about ticagrelor compared to the other ADP receptor antagonists?
it is a reversible inhibitor
not a prodrug
Where is ticagrelor commonly seen?
post-MI
What are the common agents to prevent MI/stroke?
ASA
clopidogrel
ticagrelor
prasugrel
True or false: ASA, clopidogrel, prasugrel, and ticagrelor can reduce the risk of atherosclerotic plaque rupture
false
they prevent the consequences following rupture
Where are glycoprotein IIb/IIa inhibitors used? What is the dosage form?
hospital
parenteral (IV)
What are the glycoprotein IIb/IIIa inhibitors?
abciximab
eptifibatide
tirofiban
What is the role of nitroglycerin in CAD?
manage or prevent angina
What is angina?
pain or discomfort resulting from inadequate supply of blood to cardiac muscle
How can preload be decreased with nitroglycerin?
nitroglycerin acts on veins, more blood can pool in veins
consequently decreases workload which reduces pain from angina
What are all the options for the management/prevention of angina?
nitroglycerin spray or patch
beta blockers and non-DHP CCBs
DHP CCB
Which tissue is affected by atherosclerosis?
arteries
What is the final product of the coagulation cascade?
fibrin
How strong of an effect does ASA 81mg have on prostacyclin?
very minimal effect
True or false: just like ASA, all NSAIDs are irreversible inhibitors of COX-1 and are indicated for antiplatelet actions?
false
most NSAIDs are reversible inhibitors, COX-2 selective, and not indicated for antiplatelet action
What would happen to a person with stable angina at rest? What about during exercise?
at rest: perfusion of cardiac muscle is adequate, no angina
exercise: perfusion cannot match increased cardiac workload,
angina develops
