COX Physiology

Two isophorms: COX-1 and COX-2, which produce PGE₂, PGF_2α, PGI₂, and TXA₂ from arachidonic acid. COX-1 controls most physiologic aspects of prostaglandin activity: gastroprotection, coagulation balance, etc. COX-2 is primarily used for inflammation and adaptive responses to the environment

Prostaglandin	Blood Vessel	Plts	Bronchi	Uterus
PGE2	Dilation		Dilation	Dilation
PGF2α	Constriction		Constriction	Constriction
PGI2	Dilation	Inhibition of Aggregation
TXA2	Constriction	Promotion of Aggregation

Prostaglandin Drugs

• Alprostadil is PGE₁
  • Used for ED as a penile suppository or local injection
• Misoprostol is a PGE₁ derivative
  • Used in combination with NSAIDs to decrease GI SEs and to increase uterine dilation
• Latanoprost is a PGF_1α prodrug
  • Glaucoma
• Prostacyclin is PGI₂
  • Used as a vasodilator and for pulmonary arterial hypertension
  • Avoid w/ anticoagulants

NSAIDs

Salicylates

• Aspirin
  • Comparatively high anti platelet activity
• Salsalate (DIsalcid)
  • Minimal GI SEs (dimer that is not active until in the presence of esterases in the small intestine)
• Diflunisal (Dolobid)
  • More potent analgesia, less potent antipyretic activity than ASA, 3-4x longer lasting

Arylacetic Acids

• Indomethacin
  • Highly potent
  • Many SEs
  • Acute use only
• Sulindac
  • Prodrug
  • Minimal GI SEs
  • Suitable for long-term use
• Etodolac
  • As potent as indomethacin
  • Somewhat COX-2 selective
  • Suitable for long-term use
• Diclofenac
  • As potent as indomethacin
  • Somewhat COX-2 selective
  • Inhibits lipoxygenase (leukotriene synthesis) as well

Arylpropionic Acids

• Ibuprofen
  • More potent than ASA
  • Less potent than indomethacin
• Naproxen
  • More potent than ibuprofen
  • Moderate GI irritation
• Ketorolac (Tordal)
  • Good for acute severe pain
  • Analgesia similar to opioids
  • NTE ≈ 5d consecutive use

Non-carboxylated

• Nabumetone
  • Prodrug
  • Minimal GI actvity
  • Great anti-inflammatory, minimal analgesia
• Meloxicam
  • Long-lasting, QD dosing
  • As potent as indomethacin

COX-2 Selective

• Celcoxib (Celebrex)
  • Great for pain, inflammation, fever
  • Minimal GI SEs
  • As potent as naproxen
  • Inhibition of COX-2 inhibits PGI₂ synthesis in vascular endothelia, leading to unopposed TXA₂ from plts, leading to increased clot risk

SES

• N / V
• GI Ulceration
  • Primarily caused by acidity of molecules
  • Worsened by decrease in cytoprotective prostaglandin synthesis
• AKI
• Hypersensitivity
• Reye’s Syndrome w/ Salicylates
  • Rare, but life threatening
• Tinnitus
• Dizziness
• HA