Antiplatelet Medications Flashcards
Where are platelets derived from and what is their lifespan?
The platelets normally circulate inactivated but when activated, within the platelets are ___ and ___ granules whole contents ____ are released
Recall that platelets are derived from megakaryocytes and have a lifespan of 7 days
The platelets normally circulate inactivated but when activated, within the platelets are alpha and dense granules whole contents (alpha – clotting and growth factors; dense granules – ADP, serotonin, calcium) are released
Review the process of primary hemostasis (hint: 3 A’s of primary hemostasis)
3 A’s of primary hemostasis
Adhesion: inactive platelet adhesion to vascular endothelium following vascular injury
Activation: activation of the platelet following adhesion (mediated by release of alpha and dense granules, etc etc) – this is a classic +ve feedback loop (recruitment of more platelets to form platelet plug)
Aggregation: platelet crosslinking and formation of stable fibrin clot
The majority of antiplatelet drugs work at the ___ step in primary hemostasis
The majority of antiplatelet drugs work at the activation step of primary hemostasis
Mainly one class of antiplatelet drugs works at the aggregation step of primary hemostasis: ___
Mainly one class of antiplatelet drugs works at the aggregation step of primary hemostasis: GPIs (GPIIb/IIIa inhibitors)
GPIs are very potent antiplatelet drugs because ___
GPIs are very potent antiplatelet drugs because they affect the rate-limiting step in thrombus formation/clotting
Describe the process of thrombus formation
Thrombus formation:
Formation of lipid core >> Plaque rupture >> platelet adhesion, activation, aggregation >> thrombus formation >> thrombus occlusion
The biggest risk with antiplatelet drugs is ___
The biggest risk with antiplatelet drugs is bleeding
Review the drug targets of antiplatelet drugs
**fill in the blank**
What is the function of COX-1?
___is a product of COX1 and acts as a potent vasoconstricor and platelet activator
COX-1 produces thromboxane A2 (TXA2) and prostaglandins
TXA2 is a product of COX1 and acts as a potent vasoconstricor and platelet activator
2 drugs that inhibit COX1 are ___ and ___
2 drugs that inhibit COX1 are aspirin and triflusal
Phospholipids are converted to arachidonic acid which binds to the active site of ___, resulting in production of ___. ___ is the precursor for TXA2 and PGE.
What is the MOA of aspirin in this pathway?
Phospholipids are converted to arachidonic acid which binds to the active site of COX1, resulting in production of PGH2. PGH2 is the precursor for TXA2 and PGE.
Aspirin irreversibly inhbits COX1
Fill in the blanks - what are the effects of AA in the tissues below under normal circumstances?
Normally: Aa is converted to PGEs in the gut >> gastric protection
heart (TXA2 and PGI2 via COX2) >> antithrombotic effects + vasoconstriction/vasodilation
kidney (PGE2 and PGI2) >> afferent arteriole dilation – increased blood flow – increased Na+ and water excretion
What are the effects of aspirin in the AA pathway below?
Aspirin irreversibly inhibits __ at low doses and __ at high doses
Aspirin irreversibly inhibits COX1 at low doses and COX2 at high doses
What is the role of phosphodiesterase in platelet aggregation?
Describe the MOA of dipyridamole (PDE inhibitor)
Combination of extended release dipyridamole/aspirin is used for ___
PDE increases cAMP breakdown >> increases intracellular Ca2+ >> promotes platelet aggregation (normally cAMP decreases intracellular calcium >> inhibits platelet activation and aggregation)
Dipyridamole blocks adenosine reuptake and inhibits cAMP-mediated calcium release **also inhibits PDE**
Combination of extended release dipyridamole/aspirin is used for secondary prevention of ischemic stroke
When ADP is released, it binds to the ___ and facilitates the +ve feedback loop for platelet aggregation
Describe the function of P2Y12 inhibitors
When ADP is released, it binds to the ADP receptor (P2Y12 receptor) and facilitates the +ve feedback loop for platelet aggregation
P2Y12 inh’s literally inhibit P2Y12 and stop that feedback loop
What are the indications of P2Y12 inhibitors?
Name 3 adverse effects of these drugs
P2Y12 inh’s generally used for acute coronary syndromes; percutaneous coronary intervention; also combined with aspirin following coronary stent placement or acute coronary syndrome
AEs: thrombocytopenia, bleeding, dyspnea
Name the P2Y12 inhibitors (4) (hint: -ogrel and -elor drugs)
Clopidogrel
Prasugrel
Ticagrelor
Cangrelor
Fill in the blanks
(which p2y12 inh’s are reversible? irreversible?
which ones are prodrugs?)
What CYP genotype affects the degree of activation of clopidogrel?
CYP 2C9 genotype impacts the degree of activation
**see below**
Why is prasugrel a more potent drug than clopidogrel? Prasugrel is contraindicated in pts with a history of __ or __
Prasugrel requires a one step activation by CYPs in the liver so its better than clopidogrel in that sense
Since it has better antiplatelet effects, the adverse event is increased bleeding, thus the drug is contraindicated in pts w/ history of stroke or TIA (these people have increased risk of cerebral hemorrhage as well)
A unique adverse event of ticagrelor is ___
T/F: Ticagrelor is an active drug that doesn’t require activation in the liver
A unique adverse event of ticagrelor is dyspnea
***
Remember that this drug is an active drug and does NOT require activation in the liver (so, true)
As such, its activity is largely dependent on its concentration more than the life of the platelet
Which class of antiplatelet drugs works on aggregation?
What is the MOA of these drugs?
Name one clinical indication for this drugs class
What are 2 adverse effects of these drugs?
GPIIb/IIIa inhibitors
GPIs inhibit plateler crosslinking by blocking fibrinogen >> inhibit platelet aggregation
Indicated mainly for acute Rx of STEMI
Adverse events: bleeding and thrombocytopenia
Name the drugs in the GPIIb/IIIa inhibitor class (2)
T/F: This is the most potent antiplatelet therapy
Eptifibatide
Tirofiban
