Page 181 - pharma 1 theoretical updated MNU_Neat

Clinical pharmacy 2024/2025 Level 3 Pharm D Pharmacology 1 (PO 502)
Eicosanoids

 Eicosanoids, from the Greek eikosi “twenty” are formed from precursor essential fatty
acids that contain 20 carbons and 3, 4, or 5 double bonds.

 Membrane lipids supply the substrate for the synthesis of eicosanoids and
platelet-activating factor (PAF).
Types
 Arachidonic acid (AA) metabolites, including prostaglandins (PGs),
prostacyclin (PGI2), thromboxane A (TxA2), leukotrienes (LTs).
 Eicosanoids and PAF lipids function as signaling molecules in many

biological processes, including the regulation of vascular tone, renal function,
Function
hemostasis, GI mucosal integrity, and stem cell function.

 They are also important mediators of innate immunity and inflammation.
✓ Eicosanoids are not stored but are produced by most cells when a variety of
physical, chemical, and hormonal stimuli activate phospholipase A2 that

makes arachidonate available.
✓ Arachidonic acid is the primary precursor of the prostaglandins and related
compounds, and it is present as a component of the phospholipids of cell

membranes.
✓ Free arachidonic acid is released from tissue phospholipids by the action of
phospholipase A2 via a process controlled by hormones and other stimuli.
✓ Corticosteroids can block the action of phospholipase A2, so has anti-

inflammatory effect
✓ There are two major pathways in the synthesis of eicosanoids from
arachidonic acid, the cyclooxygenase and the lipoxygenase pathways.
Synthesis ✓ Eicosanoids with ring structures (that is, prostaglandins,
Cyclooxygenase thromboxane, and prostacyclin) are synthesized via the
pathway
cyclooxygenase pathway.

COX-1 COX-2
• It is responsible for the physiologic production • It causes the elevated

PGs and thromboxane. production of PGs
• It is a constitutive enzyme that regulates normal that occurs in sites of
cellular processes, such as gastric protection, chronic disease and

vascular homeostasis, platelet aggregation, and inflammation.
reproductive and kidney functions.
Lipoxygenase ✓ Several lipoxygenases can act on arachidonic acid to form

pathway leukotrienes.
NB: Several classes of drugs, most notably NSAIDs, including aspirin, owe their principal
therapeutic effects—relief of inflammatory pain and antipyresis—to blockade of PG

formation.

| P a g e 165