ppt of eicosanoids and paf
DESCRIPTION
By ramu sankulaTRANSCRIPT
S.RAMU13H61S0108M.PHARMACYDEPT OF PHARMACOLOGY
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).
.
The eicosanoids include:
1. the prostaglandins
2. thromboxanes
3. leukotrienes
4. hydroperoxyeicosatetraenoic acids (HPETEs)
5. hydroxyeicosatetraenoic acids (HETEs).
Biosynthesis
Arachidonic acid, the most common precursor of the eicosanoids, is formed by two pathways:.
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.
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.
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)
.2. The lipoxygenase pathway produces:
HPETEs HETEs leukotrienes
RECEPTORSPROSTAGLANDINS
PGE - EP1, EP2, EP3, EP4.
PGF - FP
PGD - DP
THROMBOXANE - TP
PROSTACYCLINS
PGI - IP
LEUKOTRIENES - LT1, LT2, LT3, LT4.
Actions:Vascular smooth muscle
○ PGE2 and PGI2 are potent vasodilators in most vascular beds.
○ Thromboxane is a potent vasoconstrictor.
.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.
. Bronchial smooth muscle PGFs cause smooth muscle
contraction.○PGEs cause smooth muscle
relaxation.
. 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.
. Uterine smooth muscle. PGE2 and PGF2a
cause contraction of uterine smooth muscle in pregnant women.
. Uterine smooth muscle. PGE2 and PGF2a
cause contraction of uterine smooth muscle in pregnant women.
The nonpregnant uterusnonpregnant uterus has a more variable response to prostaglandins PGF2a causes contraction
PGE2 causes relaxation.
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.
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.
Therapeutic uses Induction of labor at term. Induction of labor is produced by:
infusion of PGF2 (carboprost tromethamine) [Hemabate] or
PGE2 (dinoprostone) [Prostin E].
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)
[[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.
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.
Treatment of Glaucoma
Latanoprost - 0.3% solution (Xalatan) Trovoprost (Travatan) Tefluprost (Zioptan)
Bimatoprost (Lumigan)
Adverse effects local pain and irritation bronchospasm gastrointestinal disturbances: nausea,
vomiting, cramping, and diarrhea.
MONTEUKAST
ZAFIRLEUKAST
PRANLEUKAST
ZILEUTON
NSAIDS
CORTICOSTEROIDS
MONTEUKAST
ZAFIRLEUKAST
PRANLEUKAST
ZILEUTON
NSAIDS
CORTICOSTEROIDS
PLATELET ACTIVATINGFACTOR
PAF also termed PAF- acether and AGEPC ( acetyl- glyceyl-ether-phosphorylcholine)
Biologically active phospholipid
BIOSYNTHESIS
Synthesized from acyl-PAF by two step process and under goes ACETYLATION DEACETYLATION
Phospholipid Arachidonic acid
acyl Co A Lys-PAF(INACTIVE)
PLA 2
acetyl hydrolase
PAF (ACTIVE) Lys-PAF (INACTIVE)
acetyl transferase
ACTIONS Vasodilatation Increased vascular permeability Chemotaxis Activation of leukocytes Aggregation of platelets Smooth muscle contraction
ANTAGONISTS
Rupatidine Lexipafant CV-3988 SM-12502 WEB-2086