Eicosanoids are a large group of autocoids derived from 20-carbon fatty acids like arachidonic acid. They include prostaglandins, thromboxanes, leukotrienes, and others. Arachidonic acid is formed from membrane phospholipids by phospholipase A2 or C. The main pathways of eicosanoid biosynthesis are the cyclooxygenase pathway producing prostaglandins and thromboxane, and the lipoxygenase pathway producing leukotrienes. Eicosanoids have diverse actions in vascular, respiratory, gastrointestinal, and reproductive systems and are involved in processes like inflammation and platelet aggregation. They have therapeutic uses such as induction of labor and treatment of peptic ul

1. S.RAMU
13H61S0108
M.PHARMACY
DEPT OF PHARM

2. Overview
 Eicosanoids are a large group of
autocoids with potent effects on
virtually every tissue in the body
 these agents are derived from
metabolism of 20-carbon,
unsaturated fatty acids (eicosanoic
acids).

3. .
 The eicosanoids include:
1. the prostaglandins
2. thromboxanes
3. leukotrienes
4. hydroperoxyeicosatetraenoic acids
(HPETEs)
5. hydroxyeicosatetraenoic acids
(HETEs).

4. Biosynthesis
 Arachidonic acid, the most common
precursor of the eicosanoids, is formed
by two pathways:.

5. Biosynthesis
 Arachidonic acid, the most common
precursor of the eicosanoids, is formed
by two pathways:
1. Phospholipase A2-mediated
production from membrane
phospholipids; this pathway is
inhibited by glucocorticoids.

6. Biosynthesis
 Arachidonic acid, the most common
precursor of the eicosanoids, is formed
by two pathways:
1. Phospholipase A2-mediated
production from membrane
phospholipids; this pathway is
inhibited by glucocorticoids.
2. Phospholipase C.

9. Eicosanoids are synthesized by two pathways:
1. The prostaglandin H synthase
(COX, cyclooxygenase) pathway
produces:
A. thromboxane
B. the primary prostaglandins
 prostaglandin E, or PGE
 prostaglandin F, or PGF
 prostaglandin D, or PGD)
C. prostacyclin (PGI2)

10. .
2. The lipoxygenase pathway produces:
 HPETEs
 HETEs
 leukotrienes

11. RECEPTORS
PROSTAGLANDINS
PGE - EP1, EP2, EP3, EP4.
PGF - FP
PGD - DP
THROMBOXANE - TP
PROSTACYCLINS
PGI - IP
LEUKOTRIENES - LT1, LT2, LT3, LT4.

12. Actions:
 Vascular smooth muscle
○ PGE2 and PGI2 are potent vasodilators
in most vascular beds.
○ Thromboxane is a potent
vasoconstrictor.

13. .
Inflammation
○PGE2 and PGI2 cause an increase
in blood flow and promote, but do
not cause, edema.
○HETEs (5-HETE, 12-HETE, 15-
HETE) and leukotrienes cause
chemotaxis of neutrophils and
eosinophils.

14. . Bronchial smooth muscle
 PGFs cause smooth muscle
contraction.
○PGEs cause smooth muscle
relaxation.

15. . Bronchial smooth muscle
 PGFs cause smooth muscle
contraction.
○PGEs cause smooth muscle
relaxation.
○Leukotrienes and thromboxane
are potent bronchoconstrictors and
are the most likely candidates for
mediating allergic bronchospasm.

16. .  Uterine smooth muscle.
 PGE2 and PGF2a
 cause contraction of uterine smooth
muscle in pregnant women.

17. .  Uterine smooth muscle.
 PGE2 and PGF2a
 cause contraction of uterine smooth
muscle in pregnant women.
 The nonpregnant uterus has a more
variable response to prostaglandins
 PGF2a causes contraction
 PGE2 causes relaxation.

18. Gastrointestinal tract
○ PGE2 and PGF2a
- increase the rate of longitudinal contraction
in the gut and decrease transit time.
○ The leukotrienes
- are potent stimulators of gastrointestinal
smooth muscle.
○ PGE2 and PGI2
- inhibit acid and pepsinogen secretion in the
stomach.

19. Blood
○ TXA2
- is a potent inducer of platelet aggregation.
○ PGI2 and PGE2
- inhibit platelet aggregation.
○ PGEs
- induce erythropoiesis by stimulating the renal
release of erythropoietin.
○ 5-HPETE
- stimulates release of histamine
○ PGI2 and PGD
- inhibit histamine release.

20. Therapeutic uses
Induction of labor at term.
 Induction of labor is produced by:
 infusion of PGF2a (carboprost tromethamine)
[Hemabate] or
 PGE2 (dinoprostone) [Prostin E].

21. Therapeutic abortion:
A.Inducing abortion in the second trimester:
 Infusion of carboprost tromethamine or
 Administration of vaginal suppositories
containing dinoprostone
B.inducing first-trimester abortion:
○ these prostaglandins are combined with
mifepristone (RU486)

22. [[
Maintenance of ductus
arteriosus
 is produced by PGE1 [Prostin VR]
infusion
 PGE1 will maintain patency of the ductus
arteriosus, which may be desirable
before surgery.

23. Treatment of peptic ulcer.
 Misoprostol [Cytotec]
○ a methylated derivative of PGE1
○ is approved for use in patients taking
high doses of nonsteroidal
antiinflammatory drugs (NSAIDs) to
reduce gastric ulceration.

24. Treatment of Glaucoma
Latanoprost - 0.3% solution
(Xalatan)
Trovoprost (Travatan)
Tefluprost (Zioptan)
Bimatoprost (Lumigan)

25. Adverse effects
 local pain and irritation
 bronchospasm
 gastrointestinal disturbances: nausea,
vomiting, cramping, and diarrhea.

26. MONTEUKAST
ZAFIRLEUKAST
PRANLEUKAST
ZILEUTON
NSAIDS
CORTICOSTEROIDS

27. MONTEUKAST
ZAFIRLEUKAST
PRANLEUKAST
ZILEUTON
NSAIDS
CORTICOSTEROIDS

28. PLATELET ACTIVATING
FACTOR

29. PAF also termed PAF- acether
and AGEPC ( acetyl- glyceyl-
ether-phosphorylcholine)
Biologically active phospholipid

30. BIOSYNTHESIS
Synthesized from acyl-PAF by
two step process and
under goes
ACETYLATION
DEACETYLATION

31. Phospholipid Arachidonic acid
acyl
Co A
Lys-
PAF(INACTIVE)
PLA 2
acetyl hydrolase
PAF (ACTIVE)Lys-PAF (INACTIVE)
acetyl transferase

32. ACTIONS
Vasodilatation
Increased vascular permeability
Chemotaxis
Activation of leukocytes
Aggregation of platelets
Smooth muscle contraction

33. ANTAGONISTS
Rupatidine
Lexipafant
CV-3988
SM-12502
WEB-2086