Learning Objectives
Differentiate between the Cyclooxygenase (COX) and Lipoxygenase (LOX) branches of the arachidonic acid cascade. Master the specific physiological effects of Prostacyclins, Prostaglandins, Thromboxane, and Leukotrienes, and identify the exact molecular targets of common anti-inflammatory pharmacological agents.
1. The Upstream Cascade: Membrane to Acid
The pathway begins at the cell membrane, where phospholipids are converted into Arachidonic Acid. This is the primary site of action for potent systemic anti-inflammatories.
| Enzyme / Step | Inhibitor | Clinical Effect |
|---|---|---|
| Phospholipase A2 | Glucocorticoids | Inhibits both LOX and COX pathways; blocks NF-κB. |
| Arachidonic Acid | N/A | The precursor for all eicosanoids. |
2. The Cyclooxygenase (COX) Branch
COX enzymes convert arachidonic acid into cyclic endoperoxides, leading to the production of prostanoids and thromboxane. These regulate vascular tone, platelet activity, and uterine contractions.
| Product | Primary Physiological Effects | Pharmacological Analog |
|---|---|---|
| Prostacyclin (PGI2) | ↓ Platelet aggregation; ↓ Vascular tone (vasodilation). | Epoprostenol |
| Prostaglandin (PGE1/2) | ↑ Uterine tone; PGE2 maintains the ductus arteriosus. | Alprostadil, Dinoprostone |
| Prostaglandin (PGF2α) | ↑ Uterine tone; ↑ Bronchial tone. | Carboprost |
| Thromboxane (TXA2) | ↑ Platelet aggregation; ↑ Vascular tone (vasoconstriction). | N/A (Inhibited by Aspirin) |
3. The Lipoxygenase (LOX) Branch
The LOX pathway produces leukotrienes, which are primarily involved in asthma, allergic reactions, and inflammatory cell recruitment.
| Product / Target | Mechanism / Inhibitor | Clinical Use |
|---|---|---|
| 5-Lipoxygenase | Zileuton | Blocks the synthesis of all leukotrienes. |
| LTB4 | ↑ Neutrophil chemotaxis. | Inflammatory recruitment. |
| LTC4, LTD4, LTE4 | Montelukast / Zafirlukast | Blocks LT receptors; used in asthma management. |
Activity:
High-Yield Mnemonics & Tips:
- PGI2 (Prostacyclin): Platelet-Gathering Inhibitor. It keeps blood flowing.
- LTB4: Neutrophils arrive “B4” (before) others. It is the primary recruiter.
- Aspirin: Irreversibly inhibits COX-1 and COX-2. Most other NSAIDs (Ibuprofen, Naproxen) are reversible.
- Celecoxib: A selective COX-2 inhibitor; spares the gastric mucosa (COX-1) but may increase cardiovascular risk.
You must be logged in to post a comment.