Stepwise mechanism of action of Aspirin showing COX inhibition and antiplatelet effect

Aspirin – Mechanism of Action

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Introduction

Aspirin, also known as acetylsalicylic acid, is a widely used Non-Steroidal Anti-Inflammatory Drug (NSAID). It’s primarily known for its analgesic (pain-relieving), antipyretic (fever-reducing), anti-inflammatory, and antiplatelet actions.

Belonging to the salicylate class, Aspirin is often prescribed for:

  • Mild to moderate pain
  • Inflammatory conditions like arthritis
  • Cardiovascular protection (to prevent clot formation)

Due to its clinical importance and frequent exam presence, understanding its mechanism of action is essential for students preparing for GPAT, NEET-PG, NIPER, MBBS, and NCLEX.

Stepwise Mechanism of Action of Aspirin

  1. Aspirin is administered (usually orally).
  2. It gets absorbed and irreversibly inhibits the cyclooxygenase enzymes – COX-1 and COX-2 by acetylating serine residues in the active site.
  3. This blocks the conversion of arachidonic acid to prostaglandin H₂ (PGH₂), the precursor of prostaglandins and thromboxanes.
  4. As a result:
    • Prostaglandin synthesis is reduced, leading to reduced inflammation, fever, and pain.
    • Thromboxane A₂ synthesis is inhibited, which reduces platelet aggregation and provides an antiplatelet effect.

Clinical Applications of Aspirin

  • Analgesic: Relief in headache, myalgia, arthralgia, and other mild to moderate pain
  • Antipyretic: Reduces fever by acting on the hypothalamic heat-regulating center
  • Anti-inflammatory: Used in rheumatoid arthritis and other inflammatory conditions
  • Antiplatelet Agent: Low-dose aspirin is used in myocardial infarction, stroke prevention, and other thrombotic conditions

Adverse Effects

  • Gastric irritation, peptic ulcers, and GI bleeding (due to COX-1 inhibition)
  • Tinnitus (especially at high doses)
  • Hypersensitivity reactions
  • Reye’s syndrome (in children with viral infections – hence contraindicated)

Aspirin vs. Other NSAIDs (e.g., Ibuprofen):

FeatureAspirinIbuprofen
COX InhibitionIrreversible (COX-1 >> COX-2)Reversible (COX-1 and COX-2)
Antiplatelet EffectStrong and long-lastingMinimal and reversible
Use in CV protectionPreferred (low dose)Not used
GI IrritationHigher (COX-1 inhibition)Lower
Duration of ActionLonger for antiplatelet (~7–10 days)Short (~4–6 hours)

MCQs for Practice

Q1. Aspirin acts by inhibiting:
A. Thromboxane synthase
B. Lipoxygenase
C. Cyclooxygenase (COX) enzymes ✅
D. Prostaglandin E synthase

Q2. Which effect of aspirin is due to inhibition of thromboxane A₂?
A. Analgesic
B. Antipyretic
C. Antiplatelet ✅
D. Anti-inflammatory

Q3. Which enzyme is irreversibly inhibited by aspirin?
A. Phospholipase A2
B. Cyclooxygenase ✅
C. Lipoxygenase
D. Thromboxane synthase

Q4. Which of the following is NOT a use of low-dose aspirin?
A. Fever
B. Stroke prophylaxis
C. Myocardial infarction prevention
D. Pain relief ✅

Q5. Which adverse effect is uniquely associated with aspirin use in children?
A. Hepatitis
B. Reye’s Syndrome ✅
C. Gastritis
D. Asthma

Q6. Which of the following explains the prolonged antiplatelet effect of aspirin?
A. It reversibly inhibits thromboxane A₂
B. It irreversibly inhibits COX-2 in liver
C. It irreversibly inhibits COX-1 in platelets ✅
D. It enhances prostacyclin synthesis

Q7. Aspirin is contraindicated in children with viral infections because of the risk of:
A. Guillain-Barré Syndrome
B. Reye’s Syndrome ✅
C. Steven-Johnson Syndrome
D. Toxic epidermal necrolysis

Q8. The antipyretic effect of aspirin is mainly due to:
A. Decreased platelet aggregation
B. Central inhibition of PGE₂ synthesis ✅
C. Blocking leukotriene formation
D. Vasoconstriction in skin vessels

Q9. The analgesic action of aspirin is primarily mediated by:
A. Direct stimulation of opioid receptors
B. Activation of adrenergic pathways
C. Inhibition of peripheral nociceptor sensitization ✅
D. CNS dopamine enhancement

Q10. Which of the following statements is TRUE regarding aspirin’s pharmacokinetics?
A. It is rapidly absorbed but poorly protein-bound
B. It has a long half-life as aspirin itself
C. It undergoes hepatic metabolism to salicylate ✅
D. It is excreted unchanged in feces

FAQs

Q1: Why is aspirin used in heart attack prevention?
A: It inhibits thromboxane A₂, reducing platelet aggregation and preventing clot formation.

Q2: Why should aspirin not be given to children with viral fever?
A: Due to the risk of Reye’s syndrome, a rare but serious condition.

Q3: Is aspirin a selective COX-2 inhibitor?
A: No, it is a non-selective, irreversible COX-1 and COX-2 inhibitor.

References

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