Question 3

Outline the mechanisms of action of anti-platelet drugs. (50% of marks) Briefly describe the mechanism of action, and pharmacokinetics of aspirin, in relation to its use as an anti-platelet drug. (50% of marks).

[Click here to toggle visibility of the answers]

College Answer

Candidates should take note of how marks are apportioned to multi part questions and to avoid rewriting the same point more than twice. Generally there was a lack of sufficient breadth in knowledge in responses given for mechanism of action of anti-platelet drugs and sufficient depth of knowledge in relation to aspirin, in particular aspirin pharmacokinetics.


In response, one might comment that if the examiners did not expect to see the same point twice, they should have asked two separate different questions.  

Mechanisms of action of antiplatelet agents:

  • COX inhibitor effects: decrease thromboxane A2 synthesis
    • TXA2 is synthesised by activated platelets
    • Without TXA2, platelet activation and aggregation is inhibited
  • ADP receptor antagonist effects: 
    • These drugs bind to the P2Y12 class of ADP receptor, a Gi-protein coupled receptor. Normally, ADP binding to this receptor produces intracellular calcium increase, degranulation and the activation of the GPIIb/IIIa complex allowing platelets to bind fibrinogen and Von Willebrand Factor.
    • Without it, platelet aggregation cannot occur normally
  • GPIIb/IIIa receptor antagonists:   
    • abciximab and tirofiban are competitive, reversible inhibitors of the most important component of platelet aggregation.
    • The GPIIb/IIIa receptor binds to fibrin, fibrinogen and Von Willebrand factor; other platelets bind to the other end of the same molecules, and become attached to each other in the process.
    • If this function is inhibited, platelet aggregation cannot proceed normally.


Class Antiplatelet agent
Chemistry Aromatic acetate
Routes of administration Oral
Absorption Oral bioavailability 50% due to first pass effect(but, well absorbed)
Solubility pKa 2.97; only slighly water-soluble
Distribution VOD=0.1-0.2 L/kg; 58% protein-bound
Target receptor COX-1 and COX-2 isoforms of the cycloxygenase enzyme
Metabolism 80% is metabolised in the liver; active metabolite (salicylic acid) is responsible for much of the analgesic and antiinflammatory effect, but has little antiplatelet activity.
Elimination Salicylic acid is eliminated in the urine; renal clearance of aspirin itself becomes more important with overdose
Time course of action Aspirin half life is only 20 minutes; half-life of salicylic acid can range from 2 to 12 hours, depending on the dose.
Clinical effect duration: 96 hours
Mechanism of action By inhibiting the activity of COX-1 isoenzyme, aspirin decreases the synthesis of trhomboxane-A2, which is a potent platelet activator. The result is a decrease in platelet activation and aggregation. This inhibition is irreversible (acetylation)
Clinical effects COX-1 inhibitor and nonselective NSAID side effects:
GI ulceration (decreased gastric mucosal pH and mucus synthesis)
Acute kidney injury (microvascular renal dysfunction)
COX-2 inhibitor side effects:
Anti-inflammatory activity is mainly due to COX-2 inhibition
Prothrombotic side effects are due to COX-2 inhibition
CCF exacerbation and hypertension.
Also the possibility of causing brinchospasm in asthmatics
Single best reference for further information Nagelschmitz et al, 2014


Nagelschmitz, J., et al. "Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers." Clinical pharmacology: advances and applications 6 (2014): 51.

Patrono, Carlo. "Aspirin as an antiplatelet drug." New England Journal of Medicine 330.18 (1994): 1287-1294.

Li, Chunjian, et al. "Reversal of the anti‐platelet effects of aspirin and clopidogrel." Journal of Thrombosis and Haemostasis 10.4 (2012): 521-528.