CELL PRODUCT
Neutrophils Leukotrienes
Macrophage/Monocyte Prostaglandins+Leukotriene
Platelets Thromboxane
Endothelial Cells Prostacyclin
CELL SPECIFICITY OF ARACHIDONIC ACID-DERIVED PRODUCTS
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Prostaglandins ClassificationPG-G & PG-H
A,B,C,D,E…I
PG Subclassification1,2,3
PGF1 &PGF
2α β
PROSTAGLANDINS[PG]
Nomenclature
Classification
Subscript
due to difference in structure of cyclopentane ring.
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Characteristic features :
PG
Show the effects near the site of
synthesis(autocrine & Paracrine effects)
Are not stored in the body
Are very potent in action. Even in minute
very short life span, are
destroyed within
seconds or few minutes
Production increases or decreases in response to
diverse stimuli or
drugs
Act as local
hormones
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PROSTAGLANDINS - FUNCTIONS
Effects on GIT
Effects on Inflammati
on
Effects on Respiratory
tract
Effects on uterus
Effects on CVS
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PROSTAGLANDINS - FUNCTIONS
PGI2
VasodilatationInhibits platelet aggregation
PGA and PGE class prostaglandins lower blood pressure.
Effects on CVS
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PROSTAGLANDINS - FUNCTIONS
PGF-BronchoconstrictionPGE-Bronchodilator
Effects on
Respiratory tract
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PROSTAGLANDINS - FUNCTIONS
PGE2
Involved in inflammatory response
Effects on Inflammati
on
Prostacyclins - Chemistry1)Prostacyclins(PGI) contain another ring between 6 th and 9th carbon atoms & They are synthesized in heart and vascular endothelial cells.
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Inhibit platelet and leukocyte aggregation
Decrease T-cell proliferation
lymphocyte migration
Induce vasodilatation
prevent clot formation
prostacycline - Functions
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First isolated from blood platelets, thrombocytes
TXA2
Subscript number denotes number of double bonds
have a six membered Oxane ring.
Most commo
n
Thromboxanes [TX]
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Increase platelet aggregation
Vasoconstriction
Mobilize intracellular calcium
Smooth muscle contraction
Bronchoconstriction
Thromboxanes - FUNCTIONS
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LEUKOTRINES WERE SO NAMED BECAUSE THEY WERE IN ITIALLY DESCRIBED IN LEUCOCYTES
Grouped into 5 classes [A to E]
Subscript number denotes number of double bonds
LTC4
Leukotrines [LT]
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Increase chemotaxis
Facilitate inflammation & allergic reactions
Contraction of smooth muscle
Bronchoconstriction (asthmatic constriction )
Vasoconstriction
Leukotrines - Functions
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Leukotrienes are a hundred times more potent than histamine which provided a rapid response to an allergen
Lipoxins
Lipoxins are a family of conjugated tetraenes also arising
in leukocytes.
They are formed by the combined action of more than
one lipoxygenase.
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Inhibition of Eicosanoid Synthesis :
NSAIDs usually do not inhibit lipoxygenase activity at concentrations that inhibit COX activity.
NSAIDs may cause more substrate to be metabolized through the lipoxygenase pathways.
This leads to an increased formation of the leukotrienes.
A 5-LOX inhibitor and antagonists of the leukotriene receptors are used clinically in asthma.
Corticosteroids also block all the known pathways of eicosanoid synthesis.
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CVS
GITNSAI
DBronchial Asthma- Ulcerative Colitis Ophthalmolo
gic
Pharmacological applications of Eicosanoids
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1)Cardiovascular uses- pulmonary arterial hypertension, peripheral vascular disease. for keeping the
ductus arteriosus open until surgery in neonates carrying
certain cardiac malformations and platelet anti-aggregating agents.
2) Digestive Uses- indicated in the treatment of gastro
duodenal ulcer and for the prevention of NSAID-induced
ulcers.
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3) Ulcerative Colitis- Mesalamine(mesalazine) or 5
aminosalicyclic acid has antiinflammatory properties in the
colon and is used in the treatment of ulcerative colitis (Crohn's disease) it
also inhibits lipoxygenases.
4)Bronchial Asthma- PGE2 agonists and leukotrienes
receptor antagonists are used for the treatment of bronchial
asthma.
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5) Ophthalmologic Use- lower
intraocular pressure
6) Anti- inflammatory use-Inhibitors of cyclo-
oxygenases include NSAID
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. NSAID The useful effects in therapeutics are-
anti-inflammatory effectanalgesic effectantipyretic effect
inhibition of platelet aggregation
and decrease of thromboembolic risk (well-known with aspirin at low
doses)
Aspirin inhibits the COX pathway and consequently diverts arachidonic acid metabolites to the LO
pathway.
This also leads to a decrease in the levels of PGE2, the anti-inflammatory PG.
LTC4 synthase overexpression further increases the number of cysteinyl LTs, tilting the balance toward
inflammation and broncho constriction
Reason for Aspirin induced Asthma
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