Lecture 15 Platelet Pharmacology Flashcards
What happens with platelets activate?
Why do they do this?
change shape - smooth discoid to spiculated and pseudopodia
increase surface area and possibility of cell-cell interaction
What is glycoprotein (GP) IIb/IIIa receptor also known as?
Where are they found?
What is the action of the GP receptor?
integrin-alpha-IIb-beta-3
50,000-100,000 copies of platelet surface
increases affinity of receptor for fibrinogen which links receptors to bind platelets together
Give examples of glycoprotein antagonists
What are the risks associated with them?
abciximab, tirofiban, eptifibatide
increased risk of major bleeding and narrow therapeutic window
define: aspirin resistance
continued secretion of thromboxane A2 by platelets in response to appropriate agonist stimulation despite therapy with aspirin at a standard dose
What are the advantages of aspirin?
reduces risk of MI, stroke and CV death in patients with atherosclerotic disease
good efficacy in inhibiting platelet TxA2 release
What is a disadvantage of aspirin?
reliant on patient compliance to ensure antiplatelet efficacy
By what mechanism do Platelet P2 receptors act in terms of platelet aggregation?
ADP activate P2Y1 receptor Gq protein
activates PLC-beta activating PKC and calcium
initiation of platelet aggregation and shape change
ADP activates P2Y12 receptor G-alpha and beta-gamma subunits
G-alpha inhibits AC from propagating cAMP
beta-gamma activates PI3 kinase
amplification of platelet activation/aggregation
amplification of granule release, procoagulant activity
ATP activates P2X1 which increases IC calcium
shape change and amplification of platelet activation
What is associated with impaired clopidogrel response?
diabetes mellitus
impaired ACP-induced platelet aggregation
What is the effect of rifampicin of clopidogrel?
pre-treatment of rifampicin increases the amount of active metabolite production
What factors affect the response to clopidogrel?
dose age weight disease states - diabetes mellitus and chronic kidney disease multi-drug interactions CYP2C19 loss/gain-of-function alleles
What is a more effective thienopyridine prodrug compared to clopidogrel?
prasugrel
What is a Tricagrelor?
first oral reversibly-binding platelet P2Y12 antagonist belonging to the class of CPTPs (cyclo-pentyl-triazolo-pyrimidines)
Compare Tricagrelor or Clopidogrel
tricagrelor has fewer incidence of CV death, MI or stroke
tricagrelor more cost-effective tricagrelor acceptable safety profile
What is the function of the P2Y12 receptor?
platelet function and arterial thrombosis
Describe Aspirin
an effective but weak antiplatelet drug targeting platelet that targets COX1
