Eicosanoids and Their Precursors

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Questions and Answers

What is the primary use of Misoprostol?

To prevent peptic ulcers in patients taking NSAIDs (correct)

As a treatment for glaucoma

To induce vasodilation in blood vessels

To enhance eyelash growth

Which of the following is a function of PGF2α?

Enhance gastric acid secretion

Cause uterine contraction (correct)

Induce vasodilation

Inhibit platelet aggregation

What medical condition is Carboprost tromethamine primarily used to treat?

Open angle glaucoma

Postpartum hemorrhage (correct)

Eyelash hypotrichosis

High blood pressure

Dinoprostone is primarily used for which purpose?

To induce labor by dilating the cervix Signup and view all the answers

What function do eicosanoids serve in the body?

They bind to receptors on cell surfaces. Signup and view all the answers

How does Enprostil function in the treatment of gastric ulcers?

As a cytoprotective agent Signup and view all the answers

What effect do PGE2 and PGF2α have when inducing labor?

They produce more adverse effects than oxytoxics Signup and view all the answers

Which prostaglandin is known to relax vascular and other smooth muscle?

PGE2 Signup and view all the answers

What condition is Latanoprost primarily used to treat?

Open angle glaucoma Signup and view all the answers

What role does PGE2 play during fetal development?

It maintains patency of the ductus arteriosus. Signup and view all the answers

What effect do NSAIDs have on prostaglandin production?

They suppress prostaglandin production. Signup and view all the answers

What is the primary role of Prostacyclin (PGI2) in the body?

Inducing vasodilation Signup and view all the answers

Which prostaglandin is associated with dysmenorrhea due to its role in uterine contractions?

PGF2α Signup and view all the answers

What is a key physiological role of PGE1?

It maintains patent ductus arteriosus in neonates. Signup and view all the answers

What is the primary mode of eicosanoid metabolism in the body?

Oxidation and reduction. Signup and view all the answers

Which eicosanoid is particularly known for reducing intraocular pressure?

PGF2α Signup and view all the answers

What are eicosanoids primarily derived from?

Essential fatty acids Signup and view all the answers

Which eicosanoid precursor is most abundant in humans?

Arachidonic acid Signup and view all the answers

Which enzyme is involved in the conversion of arachidonic acid to prostaglandin endoperoxides?

Cyclooxygenase Signup and view all the answers

What distinguishes COX-1 from COX-2?

COX-1 is expressed constitutively in most cells Signup and view all the answers

What is produced by both COX-1 and COX-2 during the cyclization of arachidonic acid?

PGH2 Signup and view all the answers

Which pathway is involved in eicosanoid synthesis after arachidonic acid is mobilized?

Isoeicosanoid pathway Signup and view all the answers

What are PGH2 and its derivative prostaglandins collectively known as?

Prostanoids Signup and view all the answers

In what two ways do prostaglandins differ from one another?

In the substituents of the pentane ring and the number of double bonds Signup and view all the answers

Study Notes

Eicosanoids

Eicosanoids are fatty acid derivatives.
Derived from the Greek word "eikosi" (twenty).
Include:
- Straight-chain derivatives (Leukotrienes)
- Cyclic derivatives (prostacyclin, prostaglandins, and thromboxane)

Precursors

Precursors are essential fatty acids with 20 carbons.
Examples:
- Eicosatrienoic acid (dihomo-y-linolenic acid)
- Eicosatetraenoic acid (arachidonic acid (AA))
- Eicosapentaenoic acid (EPA)
Arachidonic acid (AA) is the most common precursor in humans.
AA is released from membrane phospholipids by lipases from the phospholipase A2 (PLA2) type.
Mobilized AA is oxygenated by different routes:
- Cyclooxygenase (COX)
- Lipoxygenase
- P450 epoxygenase
- Isoeicosanoid pathways

Synthesis of Prostaglandin Endoperoxide Synthases (Cyclooxygenases)

Two COX isozymes convert AA into prostaglandin endoperoxides.
COX-1 is expressed constitutively in most cells.
COX-2 is inducible and its expression is stimulus-dependent.
COX-2 is up-regulated by shear stress, growth factors, tumor promoters, & cytokines.
COX-1 is responsible for prostanoids in physiological processes.
COX-2 is the major source of prostanoids in inflammation and cancer.
Both COX-1 and COX-2 promote the uptake of two oxygen molecules to form PGG2.
PGG2 is modified by the peroxidase moiety of the COX enzyme to form PGH2.
PGH1 and PGH3 are derived from homo-y-linolenic acid & eicosapentaenoic acid respectively.
Prostaglandins, thromboxane, & prostacyclin are collectively termed prostanoids, generated from PGH2.

Pharmacological Effects of Eicosanoids

Eicosanoids act locally (autocrine & paracrine).
Eicosanoids bind to receptors on the cell surface.
All Eicosanoid receptors are G protein-coupled.

Effects of Prostaglandins

PGE2 & prostacyclin (PGI2) are vasodilators.
PGE1 and its derivatives protect the gastric mucosa.
PGE1 and PGE2 relax vascular and other smooth muscle.
PGE2 is a key vasodilator in fetal development.
PGs modulate glomerular filtration, affecting arterioles and mesangial cells.
PGE2 and PGF2α are released during menstruation.
PGE2 helps in cervical ripening.
Dysmenorrhea is linked to PGF2α-induced uterine contractions.
Platelet aggregation is strongly activated by thromboxane.
PGF2a reduces intraocular pressure.

Biotransformation

Eicosanoids have short half-lives and undergo rapid metabolism.
Metabolism can be by:
- Hydration (for PGI2 & TXA2)
- Oxidation of the 15-hydroxyl group by PG 15-OH dehydrogenase
Further metabolism is by reduction & oxidation.

Clinical Uses of Prostaglandins

Alprostadil (PGE₁) is used for its smooth muscle relaxing effects:
- To maintain the patency of the ductus arteriosus in neonates.
- In the treatment of erectile dysfunction (impotence).
Misoprostol, a PGE₁ derivative, is used:
- As a cytoprotective PG to prevent peptic ulcers.
- For labor induction.
- For terminating early pregnancies.
PGE2 & PGF2α induce uterine contraction:
- Carboprost tromethamine, a PGF2α analog, is used for second-trimester abortion and postpartum hemorrhage.
- Dinoprostone (PGE2) is used to dilate the cervix during induction of labor.
- Enprostil, a synthetic analogue of PGE2, is used for duodenal or gastric ulcers.
Latanoprost, Bimatoprost, travoprost, & unoprostone are topically active PGF2a derivatives:
- Used to treat open-angle glaucoma or ocular hypertension.
- Increase aqueous humor outflow to reduce intraocular pressure.
Bimatoprost is approved for the treatment of eyelash hypotrichosis.
Prostacyclin (PGI2) is produced by the vascular endothelium.
- It is a powerful vasodilator and inhibitor of platelet aggregation.

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Description

Explore the fascinating world of eicosanoids, essential fatty acid derivatives that play crucial roles in various physiological processes. This quiz covers their types, precursors like arachidonic acid, and the synthesis pathways involving cyclooxygenases. Test your knowledge on the chemistry and biology behind these important biomolecules!