Antiplatelets

Question 1

Cyclo-oxygenase inhibitors - name, mechanisms, side effects, contraindications

Answer 1

aspirin
inhibits COX-1 mediated production of thromboxane A2 and reduces platelet aggregation - irreversible.
does not completely inhibit aggregation as there are other mechanisms, action at low non-analgesic doses, higher doses inhibit prostacyclin (PGI2) which is important in stable resting platelets. it undergoes hepatic hydrolysis to salicylic acid

increased bleeding time, Reyes syndrome so avoid <16yrs, hypersensitivity, and in the 3rd trimester can cause premature closure of ductus arteriosus

other antiplatelets and anticoags

Question 2

ADP receptor antagonists - names, mechanisms, which are reversible and which has the slowest onset of action? side effects, contraindications

Answer 2

clopidpgrel, prasugrel, ticagrelor

inhibit binding of ADP to P2Y12 receptor which inhibits the activation of GPIIb/IIIa receptors

clopidogrel and prasugrel are irreversible
clopidogrel has slow onset of action so requires a loading dose

bleeding, GI upset, and caution in renal and hepatic impairment

contraindications - clopidgrel requires CYPs for activation, other antiplatelets, anticoagulants and NSAIDs

Question 3

Glycoprotein IIb/IIIa inhibitors - name, mechanism, side effects, contraindications

Answer 3

abciximab

blocks binding of fibrinogen and VWF, targets final common pathway with more complete platelet aggregation, given iv with bolus

bleeding, thrombocytopenia, hypotension, bradycardia

antiplatelets, anticoagulants

Question 4

Phosphodiesterase inhibitors - names, mechanisms, side effects, contraindications

Answer 4

dipyridamole

inhibits cellular uptake of adenosine causing increased plasma adenosine inhibiting platelet aggregation via A2 receptors. also inhibits phosphodiesterase which prevents cAMP degradation causing inhibited expressing of GPIIb/IIIa

flushing, headache, hypersensitivity

antihypertensives, antiplatelets, anticoagulants

Question 5

fibrinolytic agents - names, uses, mechanism, side effects, contraindications

Answer 5

streptokinase, alteplase

dissolves fibrin meshwork of thrombus, binds to and activates plasmin —> plasminogen

alteplase used in acute ischaemic stroke

causes bleeding and streptokinase can only be used once as antibodies develop

contraindications - intracranial haemorrhage needs ruling out