prostoglandins

Prostaglandins Overview

  • University: College of Medicine, Al-Nahrain

  • Instructor: Ass. Prof. Dr. Farrah Rasool Jaafar

  • Department: Pharmacology

Key Topics Covered

  • Eicosanoids

    • Prostaglandins

    • Role as local mediators

    • Synthesis

    • Effects

    • Actions

    • Therapeutic uses

    • Summary

Eicosanoids

  • Types:

    • Prostaglandins

    • Thromboxanes

    • Leukotrienes

    • Hydroperoxyeicosatetraenoic acids (HPETEs)

    • Hydroxyeicosatetraenoic acids (HETEs)

  • Characteristics:

    • Short plasma half-lives (0.5 – 5 min)

    • Catabolism occurs primarily in the lungs

    • Metabolites excreted in urine

    • Not pre-synthesized; produced quickly from arachidonic acid released from membranes

Synthesis of Eicosanoids

  • Arachidonic Acid:

    • Most common precursor

    • Pathways:

      • Phospholipase A2-mediated production from membrane phospholipids (inhibited by glucocorticoids)

      • Phospholipase C

  • Prostaglandins Features:

    • Unsaturated fatty acid derivatives containing 20 carbons

    • Cyclic ring structure

Specific Synthesis Locations

  • Prostaglandin I2 (PGI2):

    • Synthesized in endothelial and vascular smooth muscle cells

  • Thromboxane:

    • Synthesized primarily in platelets

  • Leukotrienes and HPETEs/HETEs:

    • Predominantly produced in mast cells, white blood cells, airway epithelium, and platelets

Role of Prostaglandins

  • Local Mediators:

    • Act locally and rapidly metabolized at sites of action

  • Functionality:

    • Modulate inflammation, pain, and fever

    • Control physiological functions related to GI tract and reproductive processes

Synthesis Pathways

  • Main Pathways:

    • Cyclooxygenase (COX) pathway

    • Lipoxygenase pathway

  • Cyclooxygenase Enzymes:

    • COX-1: Normal physiological functions (gastric cytoprotection, vascular homeostasis, etc.)

    • COX-2: Elevated in inflammation, facilitates prostanoid production in chronic disease states

Therapeutic Uses of Prostaglandins

  • Alprostadil (PGE1):

    • Treats erectile dysfunction and maintains ductus arteriosus in neonates

  • Lubiprostone:

    • Treatment for chronic idiopathic constipation, opioid-induced constipation, and irritable bowel syndrome

  • Misoprostol:

    • Protects gastric mucosa during NSAID treatment and used off-label for labor induction

  • PGF2α Analogues:

    • Used for glaucoma treatments (e.g., Bimatoprost)

  • Prostacyclin (PGI2) Analogues:

    • Treat pulmonary arterial hypertension (e.g., Epoprostenol)

Adverse Effects and Considerations

  • Common Side Effects:

    • Nausea and diarrhea for Lubiprostone

    • Risk of abortion for Misoprostol

    • Ocular reactions for PGF2α analogs

  • Inhibition Effects:

    • Steroidal and non-steroidal anti-inflammatory drugs may induce peptic ulcers due to inhibition of prostaglandin generation

    • Possible bronchospasm from drugs inhibiting cyclooxygenase enzyme.

Summary of Therapeutic Applications

  • Prostaglandins play a crucial role in treating various conditions:

    • Inducing labor and abortion

    • Maintaining erectile function

    • Reducing intraocular pressure to treat glaucoma

    • Protecting gastric lining during NSAID therapy.

Conclusion

  • Prostaglandins are critical mediators in many physiological processes and therapeutic applications. Their balance and inhibition must be carefully managed in clinical settings.