(5A) NSAIDs: Introduction and Receptors Lesson Documents

What Are NSAIDs?

• NSAIDs = non-steroidal anti-inflammatory drugs.

• They are used for pain, especially pain associated with inflammation.

Arachidonic Acid Pathway

Arachidonic acid comes from…

membrane phospholipids.

Arachidonic Acid Pathway

Once Arachidonic acid is released, it has…

2 major oxidative pathways:

1. Lipoxygenase (LOX)

Arachidonic acid → leukotrienes

2. Cyclooxygenase (COX)

Arachidonic acid → prostaglandins/prostanoids

COX-1 vs COX-2

• COX-1 = normal/homeostatic “good COX”

  • Gut

  • Kidney

  • Platelets

  • Uterus

• COX-2 = inflammation “bad COX”

  • Inflammation

  • Kidney

  • Vessel wall

What is the COX we would ideally inhibit for inflammation?

COX-2

COX-2-selective inhibitor?

• Celecoxib (Celebrex)

• Professor explained that other COX-2-selective inhibitors were removed because of cardiovascular toxicity/heart attacks - Vioxx

Most NSAIDs are not WHAT?

are not completely COX-2 selective and inhibit both COX-1 and COX-2.

What happens if NSAIDs block the COX pathway?

→ lipoxygenase pathway remains available
→ leukotrienes can still be produced.

Professor connected leukotrienes with…

asthmatic reactions.

What are all the prostaglandins we cover?

1. PGE₂/PGF₂α - INFLAMMATORY

2. PGE₁ - PROTECTIVE

3. PGI₂/TXA₂ (prostanoid)

   1. TXA₂ = constrict + clot (COX-1)

   2. PGI₂ = relax + prevent aggregation (COX-2)

Major inflammatory prostaglandins?

PGE₂

PGF₂α

What are the Protective Prostaglandin?

• PGE₁ = GI cytoprotective

• Professor described it as the “good/happy” prostaglandin.

• made from COX 1, and if inhibited can lead to GI problems

TXA₂ vs PGI₂

TXA₂ = constrict + clot (COX-1)

PGI₂ = relax + prevent aggregation (COX-2)

He connected excessive TXA₂ relative to PGI₂ with the…

cardiovascular problems seen with some COX-2-selective inhibitors