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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objectives
Objectives
  • 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
slide3
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.
slide4
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
slide7

Naming

of Prostaglandins

slide8

Prostacyclin

Thromboxan

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
slide16

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
slide18

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 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
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