Nov23 M1-Pharmacology Antiplatelet Drugs Flashcards
3 drug groups
- inhibit Tx synthesis
- block ADP receptor
- inhibit glycoprotein IIB-IIIA
use of anti-platelet drugs
prevent thrombosis
alter evolution of ats
2 types of granules found in platelets
delta granules (contain ADP) alpha granules
mechanism of primary plug formation
- plts recon vWF and collagen and are activate
- activate plts release ADP, TxA2 and 5HT
- these substances activate platelets and activate an integrin (glycoprot IIB-IIIA) on their surface
- this integrin binds fibrinogen and fibrin
- formation of formalin aggregate
what happens to plts when activated
change shape and have processes
aspirin action
blocks covalently (irreversibly) COX-1 (acetylates serine residue near its active site) so can’t produce TxA2
why aspirin effect irreversible
platelet no nucleus, can’T prod new COX 1
why ASA less effective at higher dose (NSAID dose)
Also inhibits prostacyclin prod (prostacyclin is an endogenous anti platelet)
where ASA absorbed
stomach and upper SI
ASA overdose effect
primary metab pathway saturated. elim becomes order 0 (constant rate no matter dose). significant increase in plasma ASA
aspirin effect on bleeding time
prolonged in all patients
salicylism def + cause
reduce hearing, ringing in ears, dizziness. cause: mild overdose.
aspirin use
secondary prevention of cerebral and cardiac ischemia, MI, …
inhibitors of ADP pathway mechanism
block ADP receptor on platelet surface
inhibitors of ADP pathway: give drugs
clopidogrel, prasugrel, ticagrelor
diff between inhibitors of ADP pathway and ASA
they have no effect on PG metabolism
2 inhibitors of ADP pathway used and effect
clopidogrel, prasugrel. irreversibly block ADP receptor
how ADP activates platelets
binds two purine receptors. P2Y1 and P2Y12. both must be activated
clopidogrel effect
irreversibly blocks P2Y12 receptor
clopidogrel pharmacokinetics
given as prodrug, activated by enzymes in cytochrome P450.
why clopidogrel resistance exists
genetic variability. some patients have reduced fct variant of CYP2C19 enzyme of the cytochrome P450
when clopidogrel used with ASA and when used instead of ASA
clopidogrel in stroke
clopidogrel with aspirin in ACS (acute coronary syndrome)
prasugrel effect + diff with clopidogrel
same effect. P2Y12 blocker irreversibly.
less resistance to it
ticagrelor mechanism
blocks REVERSIBLY P2Y12
ticagrelor when
in ACS, to reduce CV death, MI and stroke (better than clopidogrel)
glycoprot IIB-IIIA fct
receptor fo fibrinogen and vWF
glycoprot IIB-IIIA inhibitors: potency and administration
best anti plt but replaced by ticagrelor and prasugrel
given by injection
abciximab charact and mechanism
Fab fragment of humanize monoclonal Ab against the receptor
eptifibatide and tirofiban mechanism
peptide (2nd is small molecule) blocker of fibrinogen binding site on the receptor
major side effect of glycoprot IIB-IIIA inhibitors
bleeding and thrombocytopenia
arterial vs venous side choice of medication
arterial side: anti platelet drug
which for stroke
anti platelet (clopidogrel) dabigatran
which for DVT
UF heparin and then warfarin
LMWH heparin if good kidney function and then warfarin
which prevention of cereb or cardiac and ischemia + MI
aspirin
which to prevent stroke if prosthetic heart valve or mitral stenosis
warfarin
which to prevent stroke in a fib
rivaroxaban
which for 6 hours after after acute STEMI
alteplase or tenecteplase
