Drug of the Day Flashcards
Common indications: aspirin
• Atrial fibrillation (AF) before considering anticoagulants
• Secondary prevention of stroke and TIA
• Secondary prevention of acute coronary syndromes (ACS)
• Post primary percutaneous coronary intervention (PCI) and stent to reduce ischaemic
complications
• Often co prescribed with other antiplatelet agents
• NSTEMI/STEMI - initial once only 300 mg loading dose – chewable is best!
acute ischaemic stroke initial 300 mg daily 2 weeks
• Gastric protection required for long term use in at risk patients (proton pump inhibitor)
MOA: aspirin
When platelet-rich thrombus forms in
atheromatous arteries and occludes the circulation.
Aspirin irreversibly
inhibits cyclooxygenase (COX) to reduce production of the
pro-aggregatory factor thromboxane from arachidonic acid
= reducing platelet aggregation and the risk of arterial occlusion.
The antiplatelet effect of aspirin occurs at low doses and lasts for the lifetime of a platelet (which does not have a nucleus to allow synthesis of new COX) and thus only wears off as new platelets are made.
Important adverse effects
Gastrointestinal irritation, GI bleeding (peptic ulcer), haemorrhage (stroke)
hypersensitivity
Contraindications: aspirin
Reye’s syndrome (life-threatening illness that principally affects liver and brain) – avoid <16 years
Hypersensitivity- had allergic symptoms
3rd trimester – premature closure of ductus arteriosus
Important drug interactions: aspirin
other antiplatelet and anticoagulants (additive/synergistic action)
• COX-1 polymorphisms result in lack of efficacy in some
Name three ADP receptor antagonists
clopidogrel
prasugrel
ticagrelor
MOA: clopidogrel
Inhibit binding of ADP to P2Y12 receptor → inhibit activation of GPIIb/IIIa receptors
independent of COX pathway
Clopidogrel and prasugrel are irreversible inhibitors of P2Y12
Prodrugs – they have active hepatic metabolites
• Clopidogrel has slow onset of action without a loading dose –
some inter-individual variability in antiplatelet action
How does MOA of ticagrelor differ from clopidogrel?
Ticagrelor and prasugrel have more rapid onset of action
• Ticagrelor acts reversibly at different site to clopidogrel
and has active metabolites
Important adverse effects: clopidogrel
Bleeding! GI upset – dyspepsia and diarrhoea
rarely - thrombocytopenia
Contraindications: clopidogrel
caution in high bleed risk patients with renal and hepatic impairment
Important drug interactions: clopidogrel
clopidogrel requires CYPs for activation
CYP inhibitors – omeprazole, ciprofloxacin, erythromycin, some SSRIs
need to consider use of other PPIs with clopidogrel
ticagrelor can interact with CYP inhibitors and inducers
caution when co prescribed with other antiplatelet and anticoagulant agents or NSAIDs –
increased bleeding risk
• clopidogrel needs stopping ~ 7 days prior to surgery in most patients
ADP receptor antagonist indications
• ADP receptor antagonists used for wide variety of presentations where antiplatelet needed
• Clopidogrel
mono therapy where aspirin is contraindicated
NSTEMI patients – 3 months
STEMI patients - up to 4 weeks
Ischaemic stroke and TIA long term secondary prevention
• Prasugrel and ticagrelor with aspirin in ACS patients (undergoing PCI) for up to 12 months
• Risk of cardiovascular events vs. bleeding risk and other antiplatelet drugs all need to be
considered when prescribing these and any other antiplatelet agents
Drug class: dipyridamole
Phosphodiesterase inhibitors
MOA: dipyridamole
dipyridamole inhibits cellular reuptake of adenosine → increased [adenosine] → inhibits platelet
aggregation via adenosine (A2) receptors
• Also acts as phosphodiesterase inhibitor which prevents cAMP degradation → inhibit expression
of GPIIb/IIIa
Adverse effects: dipyridamole
V+D, dizziness
Drug-drug interactions: dipyridamole
antiplatelets and anticoagulants, adenosine
Indications: dipyridamole
Secondary prevention of ischaemic stroke and TIAs
• Adjunct for prophylaxis of
thromboembolism following valve replacement
Stroke – modified release