Eicosanoids Study Notes

Lecture 34

Identify three major classes of eicosanoids: prostaglandins, thromboxanes, leukotrienes.
Understand the source of eicosanoids and conversion of PUFA into eicosanoids.
Describe synthesis of prostacyclins, prostaglandins, thromboxanes from arachidonic acid.
Differentiate COX1 vs COX2 enzymes and their inhibition by NSAIDs.
Explain effectiveness of COX2 inhibitors in arthritis treatment and absence of stomach upset.
Rationalize daily aspirin use for heart attack prevention and risks of Vioxx.
Summarize functions of cysteinyl leukotrienes and their role in asthma treatment.
Describe pathways for arachidonic acid release and corticosteroid inhibition.

Eicosanoids are derived from 20-carbon polyunsaturated fatty acids (PUFAs) like arachidonic acid.
Major classes include prostaglandins, thromboxanes, leukotrienes.
Released arachidonic acid is modified by phospholipase A2 for eicosanoid synthesis.

Prostaglandins have short-lived hormone-like effects, influence vasodilation/constriction, platelet aggregation, and uterine contraction.
Thromboxane A2 promotes vasoconstriction and platelet aggregation, linked to cardiovascular events.
Leukotrienes (produced by lipoxygenase) are involved in neutrophil chemotaxis and asthma pathophysiology.

COX-1: Constitutive, maintains gastrointestinal integrity.
COX-2: Inducible, active in inflammation, regulated by growth factors.
NSAIDs inhibit both COX-1 and COX-2, leading to potential side effects like stomach bleeding.

Aspirin irreversibly inhibits COX, preventing arachidonic acid metabolism to prostaglandins.
Other NSAIDs (e.g., ibuprofen) are reversible inhibitors.
Selective COX-2 inhibitors (e.g., Vioxx) aimed to reduce stomach side effects but increased heart risks.

Omega-6 (linoleic acid) metabolized to arachidonic acid; Omega-3 (linolenic acid) yields EPA and DHA.
Eicosanoids derived from omega-3 fatty acids exhibit distinct properties and health benefits compared to those from omega-6.