Antiplatelet

Question 1

Aspirin

Answer 1

Indication: antiplatelet

• NSTEMI/STEMI - 300mg loading dose, 75mg OD
• AF patients post stroke
• secondary prevention of stroke, TIA, ACS
• post PCI to reduce ischaemic complications

Class: cyclo-oxygenase inhibitor

Action: low doses inhibits COX-1 mediated production of thromboxane A2 whcih reduces platelet aggregation - irreversible

Adverse effects:
- GI irritation + bleeding (Peptic ulcer)
- haemorrhage (stroke)
- hypersensitivity
- IGRAB

Warnings:

• <16yrs - reye’s syndrome
• 3rd trimester - premature closure of the ductus arteriosus
• hypersensitivty

Interactions: other antiplatelets and anticoagulants

Other:

• does not completely inhibit platelet aggregation due to other endodgenous pathways
• absorbed by passive diffusion - hepatic hydrolysis to salicylic acid
• COX1 polymorphisms result in lack of efficacy in some
• lasts lifespan of the platlet (7-10 days) - non nucleated therefore unable to produce more of COX1
• gastric protection (PPI) required for long term use in at risk patients

Question 2

Clopidogrel/prasugrel/ticagrelor

Answer 2

Indication: dual antiplatlet therapy
- synergistic effects with aspirin and aspirin can only be given in low doses
- ischaemic stroke and TIA
- long term monotherapy where aspirin in contraindicated

Class: ADP receptor antagonists

Actions: inhibit binding of ADP to P2Y12 receptor therefore inhibits activation of GPIIb/IIIa receptors (independent of COX pathway)

Adverse effects:
- bleeding
- GI upset (dyspepsia and diarrhoea)
- trombocytopenia

Warning: high bleed risk patients with renal and hepatic impairment

Interactions:
- CYP inhibitors - omeprazole, ciprofloxacin, erythromycin, SSRIs (clopidogrel requires CYPs for activation)
- tricagrelor can interact with CYP inhibitors and inducers
- other antiplatelts, anticoagulants + NSAIDs - increase risk of bleeding

Other:
- clopidogrel/prasugrel are irreversible inhibitors of P2Y12
- ticagrelor acts reversibly at different site
- clopidogrel/prasugrel are prodrugs - active hepatic metabolites
- ticagrelor has active metabolites
- most cases stopped 7 days prior to surgery

Prasugrel: 60mg loading, 10mg OD
Clopidogrel: 600mg loading, 75mg OD
Ticagrelor: 180mg loading, 90mg BD

Question 3

Dipyridamole

Answer 3

Indication: antiplatelet

• secondary prevention of ischaemic stroke and TIA
• adjunct for prophylaxis of thromboembolism following valve replacement

Class: phosphodiesterase inhibitor

Action:

1. inhibits cellular reuptake of adenosine - increased adenosine inhibits platelet aggregation via A2 receptors
2. PDE inhibitor - prevents cAMP degradation therefore inhibits expression of GPIIb/IIIa

Adverse effects: V+D, dizziness

Interactions: antiplatelets, anticoagulants, adenosine

Question 4

Abciximab

Answer 4

Indication: antiplatelet
- specialist use in high risk percutaneous transluminal coronary angioplasty

Class: GP IIb/IIIa inhibitor

Action: blocks binding of fibrinogen and vWF - targets final common pathway therefore more complete reduction in aggregation (>80%) - i.v

Adverse effect: bleeding - dose adjusted for body weight

Interactions: other antiplatlets and anticoagulants

Question 5

Streptokinase/alteplase

Answer 5

Indication: fibrinolytic

Action: catalyse plasminogen to plasmin therefore enhance degradation of fibrin clot

Adverse effects: bleeding

Interactions: antiplatelets and anticoagulants

Other:

• alteplase (tPA) in acute ischaemic stroke
• streptokinase following STEMI
• streptokinase can only be used once - antibodies develop as it is derived from bacteria