office_hours:inflammation:episode_2 []

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====== Inflammation — Episode 2: The Arachidonic Acid Pathway ======

This episode explains the **central chemical engine of inflammation**.

Most everyday drugs patients recognize — ibuprofen, aspirin, steroids, montelukast — all work somewhere on this single pathway.

<WRAP center round important 90%>
If Episode 1 was the map,  
this is the highway everything travels on.
</WRAP>

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===== Watch the Lecture =====

<WRAP lecturevideo>
{{youtube>VIDEO_ID_HERE}}
</WRAP>

<WRAP center round important 60%>
📄 **Download Slides (PDF)** \\ 
{{:office_hours:inflammation:episode_2_arachidonic_acid.pdf|Download Slides}}
</WRAP>

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===== Step 1 — Membrane Activation =====

All inflammation begins with **cell membrane phospholipids**.

Damage or immune activation triggers:

→ **Phospholipase A₂**

This releases:

→ **Arachidonic Acid**

<WRAP center round box 90%>
No arachidonic acid = no inflammatory mediators
</WRAP>

**Drug that blocks this step:**
  * Corticosteroids

This is why steroids feel dramatically stronger than NSAIDs.

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===== Step 2 — Two Competing Pathways =====

Once arachidonic acid exists, it must choose a direction:

<WRAP center 95%>
^ Pathway ^ Enzyme ^ Products ^ What They Do ^
| COX Pathway | Cyclooxygenase | Prostaglandins & Thromboxane | Pain, fever, swelling |
| LOX Pathway | Lipoxygenase | Leukotrienes | Bronchoconstriction, mucus, asthma |
</WRAP>

Every common anti-inflammatory drug targets one of these branches.

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===== COX Pathway (Pain & Fever) =====

Produces **Prostaglandins (PGE₂, PGI₂)** and **Thromboxane (TXA₂)**

Clinical effects:

  * Pain sensitization
  * Fever generation
  * Vasodilation
  * Platelet activation

Blocked by:

  * [[eicosanoids:nsaids:start|NSAIDs]]
  * Aspirin
  * COX-2 selective inhibitors

Patients experience:
  * ↓ pain
  * ↓ fever
  * ↓ swelling

But NOT immune suppression.

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===== LOX Pathway (Airway Inflammation) =====

Produces **Leukotrienes (LTB₄, LTC₄, LTD₄, LTE₄)**

Clinical effects:

  * Bronchoconstriction
  * Airway edema
  * Mucus secretion
  * Eosinophil recruitment

Blocked by:

  * [[respiratory:drugs:leukotriene_modifiers|Leukotriene Modifiers]]

Important insight:

<WRAP center round tip 90%>
Asthma is not a prostaglandin disease — it is primarily a leukotriene disease.
</WRAP>

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===== Why Steroids Are Different =====

Steroids block:

→ **Phospholipase A₂ (upstream of BOTH pathways)**

So they reduce:

  * Prostaglandins
  * Leukotrienes
  * Cytokines
  * Immune cell migration

<WRAP center round important 90%>
NSAIDs turn off one faucet  
Steroids shut off the water main
</WRAP>

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===== Clinical Consequences =====

^ Drug Class ^ What Improves ^ What Does NOT Improve ^
| Antihistamines | Itch & allergy | Pain & arthritis |
| NSAIDs | Pain & fever | Asthma control |
| Leukotriene blockers | Asthma | Arthritis pain |
| Steroids | Almost everything | Long-term safety |

Understanding failures becomes predictable.

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===== Key Takeaway =====

<WRAP center round important 90%>
You cannot treat leukotriene disease with prostaglandin drugs —  
and you cannot treat immune disease with symptom drugs.
</WRAP>

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===== Next Episode =====

→ [[office_hours:inflammation:episode_3|Episode 3 — Histamine & Immediate Hypersensitivity]]

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===== Related =====

  * [[office_hours:inflammation:start|Inflammation Series Home]]
  * [[eicosanoids:start|NSAIDs & Leukotrienes]]
  * [[respiratory:asthma:start|Asthma Pharmacology]]
  * [[allergy:start|Allergy & Hypersensitivity]]
  * [[lectures:start|Full Lecture Series]]