Cyclooxygenase-1 (COX-1) [Neurosurgery Wiki]

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====== Cyclooxygenase-1 (COX-1) ======

[[Cyclooxygenase]]-1 (**[[COX-1]]**) is an enzyme responsible for the conversion of **arachidonic acid** into **prostaglandins**, which play a key role in maintaining physiological homeostasis.

===== Key Functions of COX-1 =====

  * **Gastrointestinal Protection**
    * Produces **prostaglandins (PGE₂, PGI₂)** that protect the **gastric mucosa** by increasing mucus and bicarbonate secretion, reducing acid secretion, and promoting mucosal blood flow.
    * COX-1 inhibition can lead to **gastric ulcers and bleeding** (a major side effect of NSAIDs).
  * **Platelet Aggregation (Blood Clotting)**
    * Produces **thromboxane A₂ (TXA₂)** in platelets, which promotes **platelet aggregation** and vasoconstriction.
    * **Aspirin irreversibly inhibits COX-1**, reducing thromboxane formation, preventing blood clots (used in cardiovascular disease prevention).
  * **Renal Function**
    * Helps regulate **renal blood flow and sodium excretion**.
    * COX-1 inhibitors may reduce renal perfusion, leading to **kidney damage**, especially in patients with compromised kidney function.
  * **Vascular Homeostasis**
    * Helps maintain **blood vessel integrity** and regulates vascular tone.

===== COX-1 vs. COX-2: Key Differences =====

^ Feature         ^ COX-1 | COX-2 |
| **Expression**  | Constitutive (always present in most tissues) | Inducible (expressed during inflammation, except in kidneys and brain) |
| **Function**    | Homeostatic (stomach lining, kidney function, platelet aggregation) | Inflammatory response (pain, fever, swelling) |
| **Inhibition Effects** | Increased GI toxicity, reduced platelet aggregation, possible kidney effects | Anti-inflammatory, analgesic, and antipyretic effects |
| **Selective Inhibitors** | Aspirin (low dose) | Celecoxib, Rofecoxib (withdrawn due to cardiovascular risks) |

===== Clinical Relevance =====

  * **NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)** like aspirin, ibuprofen, and naproxen inhibit COX enzymes to reduce pain and inflammation.
  * **COX-1 inhibition** (especially with **non-selective NSAIDs**) is associated with an increased risk of **gastric ulcers and bleeding**.
  * **COX-2 selective inhibitors** (e.g., celecoxib) were developed to minimize **GI side effects** while maintaining anti-inflammatory effects.

===== Cyclooxygenase-1 inhibitor =====
[[Cyclooxygenase-1 inhibitor]]