This document discusses eicosanoids, which are important regulatory molecules produced from arachidonic acid. There are two main classes of eicosanoids - prostaglandins/thromboxanes and leukotrienes. Prostaglandins mediate inflammation and pain sensitivity, while thromboxanes are involved in blood clotting and artery constriction. Leukotrienes attract white blood cells and are involved in inflammatory diseases like asthma. Eicosanoids have roles in processes like inflammation, blood pressure regulation, and reproduction. They act through G-protein coupled receptors on target cells.

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR, DEPT. OF PHARMACOLOGY
SSIMS & RC. 1

2. Prostaglandins and related compounds are collectively known
as eicosanoids. Eicosanoids are important regulatory
molecules
Most are produced from arachidonic acid, a 20-carbon
polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid).
The eicosanoids are considered "local hormones."
 They have specific effects on target cells close to their site
of formation. They are rapidly degraded, so they are not
transported to distal sites within the body.
There is evidence for involvement of eicosanoids in
intracellular signal cascades.

3.  Two classes: Prostaglandins/thromboxanes, and
Leukotrienes
 Prostaglandins – mediate pain sensitivity,
inflammation and swelling
 Thromboxanes – involved in blood clotting,
constriction of arteries
 Leukotrienes – attract white cells, involved
inflammatory diseases (asthma, arthritis, etc..)

5. Examples of eicosanoids:
prostaglandins, prostacyclins
thromboxanes, leukotrienes
epoxyeicosatrienoic acids.
They have roles in:
inflammation, fever
regulation of blood pressure, blood clotting
immune system modulation
control of reproductive processes & tissue growth
regulation of sleep/wake cycle.

6. Prostaglandins & related compounds are transported
out of the cells that synthesize them.
Most affect other cells by interacting with plasma
membrane G-protein coupled receptors.
Depending on the cell type, the activated G-
protein may stimulate or inhibit formation of cAMP, or
may activate a phosphatidylinositol signal pathway
leading to intracellular Ca++ release.
Another prostaglandin receptor, designated PPARg, is
related to a family of nuclear receptors with
transcription factor activity.

7.  Prostaglandin H2 Synthase production
of PGs, PGI2 & TXA2
 PG endoperoxides (PGG2 & PGH2) are
more potent & long-acting than the
PGs to which they decompose
 TXA2 formed mainly in platelets by TX
synthase mediating vasoconstriction &
platelet aggregation
 PGI2, formed mainly in endothelium
by PGI synthase opposes TXA2
COOH
COOH
O
O
OH
COOH
O
O
OOH
2 O2
2 e
arachidonic acid
PGG2
PGH2
Cyclooxygenase
Peroxidase

9. PGI2/D2/E2 →dila on of arterioles, pre-capillary sphincters & post-
capillary veins → increased blood flow & cardiac output
TXA2 is a potent vasoconstrictor
TXA2 & PGI2 are potent platelet aggregation inducer & inhibitor
respectively Vasoconstriction, Platelet aggregation, lymphocyte
proliferation, bronchoconstriction
PGI2 de-aggregate platelets clumps & reduces myocardial infarct size &
ischemic organ damage
PGI2, PGE2, & NO are simultaneously released from endothelium
PGE2 inhibits B- & T-lymphocyte activation & proliferation, inhibiting
antibodies & lymphokines production

10. Smooth muscle:
Bronchial muscle relaxation by PGE2 & PGI2, but
constriction by TXA2, LTC4 & LTD4
Human pregnant uterus is contracted by PGE1/2, and PGF2α
GIT: PGEs & PGI2 inhibit gastric acid secretion & reduce
pepsin content
They increase bicarbonate, mucus & blood flow
Increased electrolyte/water movement into intestinal
lumen (diarrhea)
TXA2 is pro-ulcerogenic

12.  Platelet Aggregation &
Thrombosis
PGI2: ( Inhibit Aggregation)
 Released by endothelial cells
 Responsible for non-adherence
of platelets to healthy blood
vessels
PGE2 & TXA2: ( Promote Clotting
Process)
Produced by platelets, accounts
for spontaneous aggregation of
platelets to thrombin, collagen at
the site of injury

13. Renal System
 PGs enhance urine
formation, natriuresis,
& kaliuresis via action
on renal blood flow &
tubules
 PGD2, PGE2, PGI2
stimulate renin release
 PGs inhibit water re-
absorption under ADH
effect

14. Nervous system
Hyperthermia by PGE2, related pyrogen-induced fever
Antipyretic action of ASA & NSAIDs is via inhibition of
COX-1, -2 & -3
Algesia induction & pain sensitization to histamine, BK
or mechanical stimuli
Analgesic action of ASA & NSAIDs is via inhibition of
COXs

15. Eicosan
oid
Major Site(s) of
Synthesis
Major Biological Activities
PGD2 mast cells
inhibits platelet and leukocyte aggregation,
decreases T-cell proliferation and lymphocyte
migration and secretion of IL-1Α and
IL-2; induces vasodilation and production of
cAMP
PGE2
kidney, spleen,
heart
increases vasodilation and cAMP production,
enhancement of the effects of bradykinin
and histamine, induction of uterine
contractions and of platelet aggregation;
decreases T-cell proliferation and lymphocyte
migration and secretion of IL-1Α and
IL-2
PGF2α
kidney, spleen,
heart
increases vasoconstriction,
bronchoconstriction and smooth muscle
contraction
.

16. PGI2, PGE2, PGD2
↑ Vasodila on, cAMP
↓ Platelet and leukocyte aggrega on, IL1 and IL2, T-
cell proliferation, lymphocyte migration
PGF2a
↑ Vasoconstric on, Bronchoconstric on, smooth
muscle contraction
TXA2
↑ Vasoconstric on, Platelet aggrega on, lymphocyte
proliferation, bronchoconstriction

17. Eicosa
noid
Major Site(s) of
Synthesis
Major Biological Activities
PGH2 many sites
a short-lived precursor to thromboxanes A2
and B2, induction of platelet aggregation
and vasoconstriction
PGI2
heart, vascular
endothelial cells
inhibits platelet and leukocyte aggregation,
decreases T-cell proliferation and
lymphocyte migration and secretion of IL-
1Α and IL-2; induces vasodilation
and production of cAMP
.

18.  Uterine Stimulation
 Carboprost (15-methyl PGF2α)
 Used by IM route for induction of abortion between
12th -20th gestational weeks
 Used at a dose of 250 μg every 1-3 hrs
 Dinoprost (PGF2α)
 Injection form for intra-amniotic administration
 Used to induce labour or abortion

19. Misoprostol is a synthetic methyl ester analogue of PGE1
Used to prevent drug-induced gastric ulceration during
NSAIDs, corticosteroid or anticoagulant therapy
It can be used alone or in combination with antacids for
duodenal ulcer treatment
Not used for pregnant women or whom are planning
pregnancy

20.  Epoprostenol (PGI2):
 It is used as a heparin replacement in some
hemodialysis patients
 Used to prevent platelet aggregation in extracorporal
circulation systems
Impotence
 Alprostadil (PGE1) was used by in jection into corpora
cavernosa to maintain erection
 Replaced by PDE-V inhibitors

21. Eicosanoid
Major Site(s) of
Synthesis
Major Biological Activities
TXA2 platelets
induces platelet aggregation,
vasoconstriction, lymphocyte proliferation
and bronchoconstriction
TXB2 platelets induces vasoconstriction

22.  LTB4
 ↑ Vascular permeability, T-cell proliferation,
leukocyte aggregation, IL -1, IL-2, IFN-g
 LTC4 and LTD4
 ↑ Bronchoconstric on, Vascular permeability, IFN-g

23. LTs have no therapeutic uses, but LTs antagonists have
Anti-asthma medications:
5-Lipoxygenase Inhibitors, e.g., zileutin
Leukotriene-receptor antagonists;
montelukast, & zafirlukast