From the Guidelines
Aspirin's primary mechanism of action is the irreversible inhibition of cyclooxygenase (COX) enzymes, specifically COX-1 in platelets, which reduces thromboxane A2 production and leads to decreased platelet aggregation and blood clot formation. This occurs when aspirin acetylates a serine residue in the active site of COX-1, preventing the contact with arachidonic acid and stopping thromboxane A2 synthesis 1. The effect is irreversible throughout the entire life span of platelet in the circulation, lasting from 7 to 10 days. Aspirin's inhibition of COX-1 also accounts for its anti-inflammatory, analgesic, and antipyretic properties. At low doses, aspirin predominantly affects COX-1 in platelets, providing cardiovascular protection, while at higher doses, it also significantly inhibits COX-2, enhancing its anti-inflammatory and pain-relieving effects 1.
Key aspects of aspirin's mechanism of action include:
- Irreversible inhibition of COX-1 in platelets, reducing thromboxane A2 production and platelet aggregation
- Inhibition of prostaglandin synthesis, accounting for anti-inflammatory, analgesic, and antipyretic properties
- Dose-dependent effects, with low doses (75-100 mg daily) predominantly affecting COX-1 in platelets and higher doses (325-650 mg) also inhibiting COX-2
- Irreversible effect on platelets lasting for their entire lifespan (7-10 days), allowing for once-daily dosing despite a short half-life of approximately 15-20 minutes in the bloodstream 1.
It is essential to consider the individual patient's risk assessment when using aspirin for primary prevention of cardiovascular disease and colorectal cancer, as the benefits and harms may vary depending on age, cardiovascular risk, and bleeding risk 1.
From the Research
Aspirin Mechanism of Action
The mechanism of action of aspirin is complex and involves the inhibition of cyclooxygenase (COX) enzymes, which are responsible for the production of prostaglandins.
- Aspirin acetylates serine-530 of cyclooxygenase-1 (COX-1), thereby blocking thromboxane A2 synthesis in platelets and reducing platelet aggregation 2.
- Aspirin also inhibits COX-2 activity, although it is less effective in doing so compared to its inhibition of COX-1 2.
- The acetylation of COX-2 by aspirin leads to the formation of 15 R-prostaglandins, which have been shown to inhibit platelet aggregation 3.
- Aspirin's inhibition of COX-1 and COX-2 results in the reduction of prostaglandin biosynthesis, which in turn leads to its anti-inflammatory, analgesic, and anti-pyretic effects 4.
COX-1 and COX-2 Inhibition
Aspirin's inhibition of COX-1 and COX-2 has different effects on the body.
- COX-1 inhibition is associated with a reduction in thromboxane A2 synthesis, which leads to a decrease in platelet aggregation and a reduced risk of thrombotic events 2.
- COX-2 inhibition is associated with a reduction in prostaglandin synthesis, which leads to a decrease in inflammation and pain 4.
- The balance between COX-1 and COX-2 inhibition is important, as excessive COX-1 inhibition can lead to gastrointestinal toxicity, while excessive COX-2 inhibition can lead to an increased risk of thrombotic events 5, 6.
Clinical Implications
The mechanism of action of aspirin has important clinical implications.
- Aspirin's antiplatelet effects make it a useful drug for the prevention of coronary artery and cerebrovascular thrombosis 2.
- Aspirin's anti-inflammatory effects make it a useful drug for the treatment of pain and inflammation 4.
- The development of selective COX-2 inhibitors has led to a reduction in gastrointestinal toxicity associated with traditional nonsteroidal anti-inflammatory drugs (NSAIDs) 6.