Prostaglandins related compounds
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Prostaglandins& Related Compounds. Objectives. Origin of ecosanoids Ecosanoids role Overview of the structure Role of phospholipase A2 Cyclooxgenase isoenzymes Inhibitors of prostaglandin synthesis Aspirin induced asthma Low –dose aspirin therapy.

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  • Origin of ecosanoids

  • Ecosanoids role

  • Overview of the structure

  • Role of phospholipase A2

  • Cyclooxgenaseisoenzymes

  • Inhibitors of prostaglandin synthesis

  • Aspirin induced asthma

  • Low –dose aspirin therapy

Prostaglandins related compounds

  • The eicosanoids are a group of molecules derived from the C20 polyunsaturated fatty acids

  • The dietary precursor of PG is linoleic acid which is elongated & desaturated to arachidonicacid

  • The eicosanoids derived compounds include the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs)and lipoxins(LXs).

  • The PGs ,TXs and prostacyclinsare collectively identified as prostanoids.

Prostaglandins related compounds
They are extremely potent compoundswith wide range of physiological, pathological & pharmacological effects

Gastric integrity& renal function

Regulate smooth muscle contraction

( SI & uterus )

Blood Vessel Diameter

Hypersensitivity reactions

Inflammatory responses

Platelet homeostasis

Properties of ecosanoids
Properties of Ecosanoids

  • They simulate hormones but:

  • Produced in very small amounts

  • Produced in almost all tissues

  • Locally rather than transported

  • Not stored

  • Extremely short half-life

  • Act through nuclear & plasma membrane receptors

Prostaglandins related compounds


of Prostaglandins

Prostaglandins related compounds



Leukotrienes lipoxins

Leukotrienes & Lipoxins

Prostaglandins related compounds



Prostaglandins related compounds

PG endoperoxide


Cyclooxygenase isoenzymes
Cyclooxygenase Isoenzymes

  • There are 2 forms of the COX activity.

  • COX-1 is expressed constitutively in gastric mucosa, kidney, platelets, and vascular endothelial cells (imp for healthy tissue).

  • COX-2 is inducible and is expressed in macrophages and monocytes ( limited number of cells) in response to inflammation. It mediates pain, hotness, redness by PG synthesis

Inhibitors of prostaglandin synthesis
Inhibitors of Prostaglandin synthesis

  • Cortisol inhibits the phospholipase A2

  • Aspirin, indomethacin , and phenylbutazone (NASIDs) inhibit both COX1 & COX2

  • Aspirin toxicity is due to COX1 inhibition reflected on damage of stomach, kidneys and impaired clotting of blood.

  • Selective inhibitors of COX2 as celebrix but the use of some of them may lead to increased risk of heart attack

Prostaglandins related compounds

  • Leukotrienes are mediators of allergic response and inflammation

  • Aspirin-induced asthma is a response to overproduction of leukotrienes with NASIDs use.

  • NASIDs also favor synthesis of lipoxins lipid mediator with anti-inflammatory effects

Prostaglandins related compounds

Prostaglandins related compounds

  • TXA2

  • Produced in platelets

  • induces platelet aggregation,

  • Vasoconstriction

  • Mobilizes intracellular calcium

  • Contraction of smooth muscles

  • PGI2

  • Produced in vascular endothelial cells

  • inhibits platelet aggregation

  • induces vasodilation and production of cAMP

Role of prostaglandins in platelet homeostasis
Role of Prostaglandins in Platelet homeostasis

Role of aspirin
Role of Aspirin

  • Aspirin has antithrombogenic effect.

  • It inhibits TXA2 synthesis from arachidonic acid in platelets by irreversible acetylation & inhibition of COX-1

  • This irreversible cannot be overcome in anucleated platelets but can be overcomed by endothelial cells b/c they have nucleus

  • This is the basis of low-base aspirin therapy