NSAIDs exert their anti-inflammatory effect primarily by inhibiting which enzyme?

Explanation

## Mechanism of NSAID Anti-inflammatory Action **Key Point:** NSAIDs inhibit cyclooxygenase (COX) enzymes, which catalyze the first committed step in prostaglandin and thromboxane synthesis from arachidonic acid. ### Arachidonic Acid Metabolism Pathway ```mermaid flowchart TD A[Arachidonic Acid]:::outcome --> B{Enzymatic pathway}:::decision B -->|COX pathway| C[Cyclooxygenase]:::action B -->|LOX pathway| D[Lipoxygenase]:::action C --> E[Prostaglandins & Thromboxane]:::outcome D --> F[Leukotrienes]:::outcome E --> G[Anti-inflammatory effect]:::action F --> H[Pro-inflammatory effect]:::action ``` ### COX Isoforms and Their Functions | COX Isoform | Tissue Distribution | Function | NSAID Effect | | --- | --- | --- | --- | | COX-1 | Constitutive (GI, platelets, kidney) | Homeostatic | Inhibited by all NSAIDs | | COX-2 | Inducible (inflammatory sites, CNS) | Pro-inflammatory | Selectively inhibited by coxibs | **High-Yield:** COX inhibition → decreased prostaglandin E₂ (PGE₂) and prostacyclin (PGI₂) → reduced inflammation, pain, and fever. This is the cornerstone of NSAID pharmacology tested in NEET PG. **Mnemonic:** **COX** = **C**yclooxygenase — the target enzyme for NSAIDs. **Clinical Pearl:** Lipoxygenase inhibition (by leukotriene antagonists like montelukast) is a separate anti-inflammatory strategy used primarily in asthma, not the primary mechanism of NSAIDs. [cite:Harrison 21e Ch 297]