Regarding the mechanism of action and pharmacological effects of NSAIDs, all of the following are true EXCEPT:

Question

Accepted Answer

C. NSAIDs inhibit prostaglandin synthesis by irreversibly blocking the active site of cyclooxygenase enzymes. ## Mechanism of NSAID Action

**Key Point:** NSAIDs inhibit cyclooxygenase (COX) enzymes, but the nature of inhibition differs by drug class.

### COX Inhibition: Reversible vs Irreversible

| Feature | Most NSAIDs | Aspirin |
|---------|-------------|----------|
| Type of inhibition | Reversible, competitive | Irreversible, covalent |
| Duration of effect | Short (hours to days) | Long (7–10 days for platelets) |
| Recovery mechanism | Enzyme dissociation | New protein synthesis required |
| Platelet recovery | Within 24–48 hours | 7–10 days |

**High-Yield:** Aspirin is the ONLY NSAID that irreversibly acetylates COX enzymes. All other NSAIDs (ibuprofen, naproxen, indomethacin, meloxicam, etc.) are reversible, competitive inhibitors.

### COX-1 vs COX-2 Selectivity and Clinical Effects

**Key Point:** Both COX-1 and COX-2 inhibition contribute to therapeutic and adverse effects.

- **COX-1 inhibition** → decreased thromboxane A₂ (TXA₂) in platelets → antiplatelet effect (correct)
- **COX-2 inhibition** → decreased prostaglandin E₂ (PGE₂) and prostacyclin → analgesic, anti-inflammatory, antipyretic effects (correct)
- **COX-1 inhibition** → decreased protective PGE₂ in gastric mucosa → increased ulcer risk (correct)

**Clinical Pearl:** Selective COX-2 inhibitors (coxibs: celecoxib, rofecoxib) reduce GI toxicity by sparing COX-1–mediated gastric protection, but increase cardiovascular thrombotic risk due to unopposed TXA₂ (correct statement).

### Why the Correct Answer is Wrong

The statement "NSAIDs inhibit prostaglandin synthesis by **irreversibly** blocking the active site of cyclooxygenase enzymes" is FALSE. Only **aspirin** achieves irreversible inhibition through acetylation of serine residues. All other NSAIDs are reversible, competitive inhibitors that dissociate from the enzyme.

**Mnemonic:** **ASPIRIN = Acetylates Serine, Permanent Irreversible Reaction IN NSAIDs** — it's the exception, not the rule.

[cite:KD Tripathi 8e Ch 12]

Answer

A. Selective COX-2 inhibitors have a lower risk of gastrointestinal ulceration compared to non-selective NSAIDs

Answer

B. COX-2 inhibition is primarily responsible for the analgesic and anti-inflammatory effects of NSAIDs

Answer

D. Inhibition of COX-1 in platelets leads to decreased thromboxane A2 production and antiplatelet effects

Regarding the mechanism of action and pharmacological effects of NSAIDs, all of the following are true EXCEPT:

Explanation

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