Prostaglandins

Prostaglandins are lipid mediators derived from arachidonic acid. They have diverse roles in inflammation, pain, reproduction, and cardiovascular regulation.

Introduction

Prostaglandins are synthesized in almost all nucleated cells. They act as local hormones, mediating processes like inflammation, fever, and regulation of blood flow.

Synthesis

Arachidonic acid is released from membrane phospholipids by phospholipase A2.
COX enzymes convert arachidonic acid into prostaglandin H2 (PGH2).
PGH2 is further transformed into specific prostaglandins (PGE2, PGF2α, PGI2, TXA2).

COX-1: Constitutive enzyme involved in homeostasis.

COX-2: Inducible enzyme expressed during inflammation.

Natural and Synthetic Prostaglandins

Natural Prostaglandins

PGE2: Vasodilation, fever, and inflammation.
PGF2α: Uterine contraction and intraocular pressure regulation.
PGI2: Inhibits platelet aggregation and causes vasodilation.
TXA2: Promotes platelet aggregation and vasoconstriction.

Synthetic Prostaglandins

Misoprostol: Prevents NSAID-induced ulcers.
Carboprost: Used in postpartum hemorrhage.
Dinoprostone: Induces labor and cervical ripening.

Inhibitors of Prostaglandins

NSAIDs: Inhibit COX enzymes, reducing prostaglandin synthesis (e.g., aspirin, ibuprofen).
Selective COX-2 Inhibitors: Minimize gastrointestinal side effects (e.g., celecoxib).
Corticosteroids: Inhibit phospholipase A2, reducing arachidonic acid release.

Effects of Prostaglandins on Various Organs

Cardiovascular System: PGE2 and PGI2 cause vasodilation; TXA2 causes vasoconstriction.
Reproductive System: PGF2α causes uterine contraction; PGE2 aids in cervical ripening.
Respiratory System: PGE2 causes bronchodilation; PGF2α causes bronchoconstriction.
Gastrointestinal Tract: PGE2 increases mucus and bicarbonate secretion, protecting the stomach lining.
Renal System: PGE2 and PGI2 increase renal perfusion and sodium excretion.

Therapeutic Uses

Induction of labor and cervical ripening (Dinoprostone).
Management of postpartum hemorrhage (Carboprost).
Prevention of NSAID-induced ulcers (Misoprostol).
Treatment of pulmonary hypertension (Epoprostenol, PGI2).
Glaucoma treatment (Latanoprost, a PGF2α analog).
Treatment of erectile dysfunction (Alprostadil, PGE1): Causes vasodilation, aiding penile erection.
Maintenance of ductal patency in PDA (Patent Ductus Arteriosus): Alprostadil keeps the ductus arteriosus open in neonates.

Adverse Effects

Gastrointestinal discomfort (e.g., diarrhea, nausea).
Uterine hyperstimulation leading to fetal distress.
Hypotension and dizziness due to vasodilation.
Bronchospasm in asthmatic patients.
Headache and flushing with PGI2 analogs.

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