Antiplatelet Flashcards
what is 1 caution over drug-drug interactions for aspirin
increase risk of bleeding if taken w other antiplatelet/anticoagulant
how long does it take to replace functional COX2
3-4hrs
what is 2 caution when using clopidogrel
- pt w increase risk of bleeding
- variant elles of CYP2C19, which reduced metabolism to active metabolite & diminished drug response
list examples of drug-drug interactions with clopidogrel that increase the antiplatelet effect and risk of bleeding
- warfarin/NSAIDS/salicylates increase the risk of bleeding
- rifamycin increase drug effect
list examples of significant drug-drug interactions with ticagrelor
- anticoagulant/fibrinolytics/long term NSAIDS therapy
- increase risk of bleeding - aspirin >100mg/day
- reduce drug effect but increase risk of bleeding - CYP3A inducer
- reduce drug level & effect - CYP3A strong inhibitor
- increase drug level & risk of a/e
what is the pharmacokinetic of ticagrelor
onset: 20-30min
peak: 2-3hrs
duration: 2-3 days
list 2 cautions over the use of dipyridamole as an antiplatelet agent
- hypotension
- severe CAD
list 3 drug-drug interactions of dipyridamole when used as an antiplatelet agent
- anti-arrythmic effect as drug increase cardiac adenosine level & effect
- worsen myasthenia gravis as drug decrease cholinesterase inhibitor
- increase risk of bleeding if taken w heparin/antiplatelet/anticoagulant
list the adverse effects of dipyridamole when used as an antiplatelet agent
- headache
- hypotension
- flushing
- dizziness
- GI disturbance eg. diarrhoea, nausea/vomiting
why are the antiplatelet effects of aspirin stronger when it is used at a low dose than when it is used at a high dose
once COX1 is inhibited, it takes 7-10 days to produce newly functional COX1
explain how aspirin works as an antiplatelet drug
it is a irreversible COX inhibitor (COX1 > COX2), therefore inhibit the production of TXA2, resulting in decrease platelet aggregation
what is the 7 a/e of clopidogrel
- haemorrhage/bleeding (including ICH)
- easy bruising
- dyspnea
- dyspepsia(~5%)
- rash (~5%)
- bronchospasm
- hypotension
name 1 example of an irreversible cyclooxygenase-1 (COX-1) inhibitor used as an antiplatelet drug
aspirin
what is the MOA of clopidogrel
it is a pro drug w an active metabolite that binds irreversibly to P2Y12 receptors
drug require the activation of CYP2C19, resulting in
- interindividual variability
- slow onset
list 3 class of antiplatelet drugs
- adenosine reuptake & PDE3 inhibitor (eg. dipyridamole)
- irreversible COX inhibitor (eg. aspirin)
- ADP P2Y12 receptor inhibitor (eg. clopidogrel, ticagrelor)
explain the effect of dipyridamole as a vasodilator
it is a vasodilator as it also inhibit adenosine & PDE in VSMC, this result in a dose limiting a/e which limit the efficacy of drug, therefore
- it is use as an adjunct therapy with other antiplatelet/anticoagulant
- can be administered IV as an alternative for myocardial stress perfusion imaging
why does pt on aspirin have a high risk of upper GI bleed
inhibition of COX1 inhibit the production of protective PG in stomach
what is 1 contraindication when using clopidogrel
pt w active bleeding
what is the pharmacokinetic of clopidogrel
onset: 2-4hrs
peak: 6-8hrs
duration: 7-10 days
what is the pharmacokinetic of aspirin on once daily dosing
onset: 3-4hrs
peak: 2-3 days
duration: 7-10 days
what are the processes involving blood cells that occur during primary haemostasis
platelet activation & aggregation occur during primary haemostasis
list 4 contraindications of ticagrelor
- breast feeding women
- hx of ICH
- active pathologic bleeding
- severe hepatic impairment
list 3 caution when giving ticagrelor
- pt w risk of bleeding
- elderly
- moderate hepatic impairment
why is dipyridamole often administered in a modified- or extended-release preparation
due to drug having a short half life, resulting in a duration of action of 3hrs
therefore given as a modified release to prolong the duration of action
list 2 adverse effects of aspirin when used as an antiplatelet agent
- upper GI bleed
- increase risk of bleeding/bruising
what is the MOA of dipyridamole
it inhibit platelet aggregation & activation by increasing cAMP within the platelets via
- inhibiting adenosine reuptake, which increase plasma adenosine activation of a2 receptors on platelets
- inhibit PDE3, which prevent the degradation of cAMP within platelets
what is the MOA of ticagrelor
drug w it metabolite bind reversibly to other binding sites (not ADP binding site) on P2Y12 to inhibit G protein activation & signalling
what is the major caution over the use of aspirin
caution over the use of patient w bleeding/platelet disorder
which class of drugs inhibit primary haemostasis
antiplatelet
what is the pharmacokinetic of dipyridamole
onset: 20-30min
peak: 2-2.5hrs
duration: ~3hrs
name at least 2 examples of ADP P2Y12 receptor inhibitors used as antiplatelet drugs
- clopidogrel
- ticagrelor
list examples of drug-drug interactions with clopidogrel that decrease the antiplatelet effect
macrolides/mod-strong CYP2C19 inhibitor reduce drug effect
name 1 example of an adenosine uptake and PDE3 inhibitor antiplatelet agent
dipyridamole
list 5 a/e of ticagrelor
- haemorrhage/bleeding (eg. ICH)
- dyspnea
- easy bruising
- cough
- bradycardia
what is the haemostasis process
- when blood vessel is damage, it vasconstrict to minimize blood loss
- primary haemostasis - platelet adhere to the site of injury & release ADP & TXA2 to stimulate platelet activation & aggregration
- secondary haemostasis - thrombin convert fibrinogen → fibrin to form a mesh
- clot stabilization - thrombin convert XIII → XIIIa in the presence of ca2+, which then crosslink w fibrin to create a more stable clot
