Arachidonic Acid Pathway

Question 1

Basic Path

Answer 1

Membrane phospholipids –> AA via phospholipase A2

AA –> prostacyclins, prostaglandins and thromboxane via COX 1 and COX2

AA –> leukotrienes via 5-lipoxygenase

Question 2

COX Path Products

Answer 2

Prostacyclin - PGI2 - dec platelet aggregation and dec vascular tone (both I for inhibition)

PGE1 - dec vascular tone

PGE2/OGF2 - inc uterine tone

TXA2 - inc platelet aggregation and inc vascular tone (want to dec flow when making platelet plug)

Question 3

Lipoxygenase Path Products

Answer 3

Leukotrienes

LTB4 - neutrophil chemotaxis (neutrophils “before” other cells)

LTC4, LTD4, LTE4 - inc bronchial tone

Question 4

Acetaminophen

Answer 4

MOA: reversible inhibition of COX

Mainly in CNS (peripheral inactivation)

Anti-pyretic, analgesic but not anti-inflammatory

NAPQI depletes glutathione (give N-acetylcysteine to regenerate glutathione)

Question 5

Aspirin

Answer 5

MOA: Irreversibly inhibits COX enzymes by covalent acetylation

Dec synthesis of TXA2 and prostaglandins to inc bleeding time

Lasts until new platelets made (8-10 days)

Side effects - gastric ulcers, tinnitus, Reyes

Question 6

Celecoxib

Answer 6

MOA: selective COX2 inhibitor

COX2 (inflammatory cells and vessels) but spares COX1 (GI mucosa)

Used in RA, OA

Question 7

NSAIDs

Answer 7

Ibuprofen, naproxen, indomethacin, ketorolac, meloxicam, piroxicam

MOA: reversible inhibition of COX enzymes to block prostaglandin synthesis

ANTI-INFLAMMATORY, anti-pyretic and analgesic

Indomethacin used to close PDA

Side effects - gastric ulcer, renal ischemia (afferent), aplastic anemia