Pharmacology of Antiplatelet Medications Flashcards
What are the three functions of platelets
Platelet adhesion, Platelet activation, platelet aggregation
T/F: Platelet receptors usually have interactions with just injured endothelium
True
What are the two main receptors of platelet adhesion
Collagen via GPVI, vWF via GP1b
T/F: The collagen and Gp1B vW receptors are only used for platelet adhesion
False: The collagen and Gp1B vW receptors also aid in platelet activation along with platelet adhesion
What protein is a potent activator of platelets, what receptors do this
Thrombin, PAR 1 and PAR 4
Why are alpha-2 and beta-1 receptors on platelets leading to activation
There could possibly be a high catecholamine surge due to vascular injury promoting a coagulation state
What are platelet receptor agonist for other platelet receptors that cause activation of the platelet
ADP: P2Y12 and P2Y1 receptors, Serotonin: 5-HT2A receptor, Thrombixin: TPa and TPb receptor
What occurs once the platelet is activated
The platelet will undergo a conformational change that exposes GP2b/3A receptor
How does the exposure of GP2b/3A receptor and Fibrinogen receptor lead to aggregation
The receptors bind to fibrinogen molecules also bound to GP2b/3A receptors causing binding to other platelets forming a blood clot
What is the average life span of circulating platelets
5 to 9 days
What leads to thrombus formation
Clotting cascade turns fibrinogen to fibrin clot
T/F: Aspirin is the best antiplatelet medication becuase it can be used for primary and secondary prevention of many different events
True
What is the common antiplatelet drug class used aside from Aspirin, what is the most common medication in the drug class
P2Y12 inhibitors, Clopidogrel
What are the P2Y12 inhibitor drugs besides clopidogrel, what are they usually used for, which only has one indication
Prasugrel, Ticagrelor, Cangrelor/ Secondary prevention of acute coronary syndrome and vascular procedure/ Cangrelor is only indicated for vascular procedure and not other secondary preventions
What are the GP2A/3b inhibitor drugs, what are they indicated for
Abciximab, Eptifibatide, Tirofiban/ Secondary prevention of acute coronary syndrome and vascular procedure
T/F: GP2A/3b inhibitor drugs can be taken on a monthly regimen
False: These drugs are only given IV and for vascular procedure
What are the phosphodiesterase inhibitors, which is used with Aspirin, for what indication
Dipyridamole and Cilostazol, Dipyridamole, Stroke and TIA
What causes prostaglandin H2 to be formed in the body
arachidonic Acid is converted by COX-1 and COX-2 into prostaglandin G2, prostaglandin G2 will be converted by peroxidase to Prostaglandin H2
What are the possible two most common lipids that prostaglandins are converted to, what enzymes does each conversion
Thrmoboxane A2 (TXA2)/ Thromboxane synthase, Prostacyclin (PGl2)/ Prostacyclin synthase
What are the functions of Thromboxane A2 (TXA2)
Vasoconstriction, Platelet activation and aggregation
What are the functions of Prostacyclin (PGl2)
Vasodilation, Inhibits platelet activation
T/F:Prostaglandin H2 can cuase inflammation through formation into PGl2 as well as other prostaglandins
True
How much aspirin is needed to inhibit COX-1
50-325 mg/day
What is the MOA of aspirin
Acetylates serine residue near active site of COX-1 and irreversibly inhibits TxA2 production for lifespan of platelet
T/F: Giving more aspirin leads to more inhibition of platelet activity
False: Complete inactivation of COX-1 is with 75 mg/day and increasing more will not cause more effects
How often does Aspirin resistance happen
1/4 of patients
What are the proposed mechanisms for nonresponses to Aspirin
COX-1 changes and drug interactions with NSAIDs
Which P2Y12 inhibitor is a prodrug, what enzymes cause metabolism
Clopidogrel, CYP219 twice
T/F: Genetic polymorphism of CYP12 can effect how well clopidogrel works and mostly effects Asians
True
Which PY12 inhibitor is first metabolized by esterases in the blood stream and CYP12
Prasugrel
Which PY12 inhibitors are drugs as soon as they are in the body
Ticagrelor
T/F: Clopidogrel is a better platelet inhibitor than prasugrel
False: Prasugrel cause 90% platelet effect compared to Clopidogrel reaching peak effect at 60%
T/F: Clopidogrel can reach its max platelet inhibition sooner if the loading dose is increased
True
What is the max platelet aggregation for Ticagrelor
90%
Why is the peak effect of Clopidogrel delayed compared to the newer genrations
It needs conversion by the liver to be effective
Which PY12 inhibitor is IV
Cangrelor
What is the dose of Ticagelor
180mg/90mg BID
What drugs do Ticagelor interat with
Strong CYP3A4 inhibitors and inducers
T/F: Clopidogrel and Prasugrel have irreversible receptor binding last at least 3 to 10 days
True
T/F: GP2A/3B receptors can be around 50K to 100K on platelets andare prime targets for antithrombosis
True
What are the GP2A/3B inhibitor medications
Abciximab, Eptifibatide, Tirofiban
What is the duration of action of abciximab, eptifibatide, tirofiban
two days, 2-4 hours, 3-4 hours
Which of the GP2A/3B inhibitors are renally eliminated
Eptifibatide and Tiofiban
What happens intracellularly when ADP binds to the P2Y12 and P2Y1 receptors causing regulation of platlet activation
Adynlate cyclase converts ATP and GTP into cAMP and cGMP leading to decreased platelet activation
How do phospodiesterases cause increase platelet activation
Decreases cAMP and cGMP by converting them to AMP and GMP
What are the phosphodiesterase inhibitors
dipyridamole and cilostazol
What is a huge antiplatelet adverse reaction
bleeding (gastrointesitnal, intracranial, vascular access sites)
What antiplatelet drug class have the highest incidence of thrombocytopenia, which particular one needs the most caution
GP 2b/3a inhibitors, Abciximab
T/F: Clopidogrel can cause thrombotic thrombocytopenia pupura (TTP)
True
T/F: Ticagrelor can cause ventricular pause and Ticlopidne can cause myelosuppresion
True
