This presentation provides an overview of prostaglandins, including their chemistry, biosynthesis, degradation, actions, and pathophysiological roles. Prostaglandins are derived from arachidonic acid and have diverse functions in the cardiovascular, gastrointestinal, renal, and reproductive systems. They are involved in processes like platelet aggregation, smooth muscle contraction, and inflammation. The synthesis of prostaglandins is regulated by the enzymes COX-1 and COX-2, and can be inhibited by NSAIDs, resulting in potential uses for conditions like ulcers, glaucoma, and induction of labor.

1. Presentation by - Aditi Sharma
M. Pharm. Pharmacology (1st sem)
Class Roll No. - 3
(2020-21)
Institute of Pharmaceutical Sciences
Kurukshetra University, Kurukshetra
Title- Prostaglandins

2. Introduction:-
● Prostaglandins are biologically active derivatives of
20-Carbon polyunsaturated essential fatty acids
(e.g. arachidonic acid) that are released from cell
membrane phospholipids.
● Also called as eicosanoids.

3. Chemistry, biosynthesis and degradation:-
● Chemically PGs may be considered to be derivatives of
Prostanoic acid, though prostanoic acid naturally does not occur
in the body.
● It has a 5 membered ring and two side chains projecting in
opposite directions at right angle to the plane of ring.
● Chemically, PGs may be considered to be derivatives of prostanoic acid, though prostanoic acid does not naturally occur in the body.

4. ● In the body, PGs are derived from 5,8,11,14-eicosatetraenoic acid i.e. arachidonic acid.
● During PG synthesis, two of the four double bonds of arachidonic acid get saturated in the process of
cyclization, leaving two double bonds in the side chain.

5. Thus, subscript 2 prostaglandins are most important in man e.g.
PGE2, PGI2, TXA2 etc.
● Cyclooxygenase (COX) Pathway generates eicosanoids with a
ring structure (PGs, TXs, Prostacyclins), while Lipoxygenase
(LOX) pathway produces open chain compounds i.e.
leukotrienes.

7. ● COX is known to exist in two isoforms, COX-1 and COX-2. Both these forms catalyse the same
reactions.
● COX-1
○ Constitutive enzyme in most cells
○ Synthesized inside the cells
○ Eicosanoids produced by this enzyme, participate in physiological functions e.g. mucus
secretion for protection of gastric mucosa, haemostasis and maintenance of renal
function.
● COX-2
○ Present in insignificant amounts
○ Inducible by cytokines, growth factors and other stimuli during the inflammatory
response.
○ Eicosanoids produced by COX-2 lead to inflammatory or other pathological changes.

8. Inhibition of synthesis-
● Synthesis of COX products can be inhibited by NSAIDs.
● Aspirin acetylates COX at a serine residue and causes irreversible inhibition, while other
NSAIDs are competitive and reversible inhibitors.
● Most NSAIDs are non selective COX-1 and COX-2 inhibitors, but some later ones like
Celecoxib, etoricoxib etc. are selective for COX-2.
● Glucocorticoids inhibit the release of arachidonic acid from membrane lipids, hence
indirectly reduce production of all eicosanoids.

9. ● Biotransformation of amino acids occurs rapidly in most
tissues but fastest in the lungs.
● First, a specific carrier-mediated uptake into cells occurs,
then the side chains are oxidised and double bonds are
reduced in a stepwise manner to yield inactive metabolites,
which are excreted in urine.
Degradation-

10. Actions and pathophysiological roles-
● CVS-
○ PGE2 and PGF2α cause vasodilation mostly.
○ Increase cardiac output by reflex action.
○ PGG2 and PGH2 are inherently vasoconstrictors but often produce vasodilation or a
biphasic response due to rapid conversion to other PGs.
● Platelets-
○ TXA2 - A potent inducer of aggregation and release reaction
○ PGG2 and PGH2 are proaggregatory.
○ PGI2 - inhibitor of platelet aggregation
○ PGD2 - anti-aggregatory but less potent than PGI2

11. Role- TXA2 produced by platelets and PGI2 produced by vascular endothelium probably
constitute a mutually antagonistic system preventing aggregation of platelets while in
circulation and inducing aggregation on injury, when plugging and thrombosis are
needed.
● Uterus-
○ PGE2 and PGF2α - uniformly contract uterus (invivo)
○ But in in-vitro uterus- only PGF2α contracts whereas PGE2 relaxes non-
pregnant but contracts pregnant uterus.
○ Role-
■ Initiation of labour
■ Transport of sperm and facilitation of fertilization
■ Dysmenorrhoea

12. ● Bronchial muscles-
○ PGF2α, PGD2 and TXA2 - potent bronchoconstrictors
○ PGE2 - powerful bronchodilator
○ PGI2 - produces mild dilatation
● GIT-
○ In isolated preparations, longitudinal muscle of gut is contracted by PGE2 and PGF2α
while the circular muscle is either contracted (by PGF2α) or relaxed (by PGE2).
○ PGE2 acts directly on the intestinal mucosa and increases water, electrolyte and
mucus secretion.
○ Role-
■ Markedly decreases acid secretion
■ Mucus secretion is increased, hence anti-ulcerogenic.

13. ● Kidney-
○ PGE2 and PGI2 increase water, Na+ and K+ excretion and have a diuretic effect.
○ Cause renal vasodilatation and decrease tubular reabsorption.
● CNS-
○ PGs injected i.v. penetrate brain poorly, but if injected intracerebroventricularly PGE2
produces a variety of effects- sedation, rigidity, behavioural changes and marked rise in
body temperature.
○ PGI2 also induces fever.
● Eye-
○ PGF2α induces ocular inflammation and lowers intraocular tension by enhancing uveoscleral and
trabecular outflow
○ Role- Locally produced PGs appear to facilitate aqueous humar drainage.

14. Uses of prostaglandins Side effects
● Abortion
● Induction of labour
● Cervical ripening
● Postpartum haemorrhage
● Peptic ulcer
● Glaucoma
● To maintain patency of ductus arteriosus
● To avoid platelet damage
● Nausea
● Vomiting
● Watery diarrhoea
● Uterine cramps
● Vaginal bleeding
● Shivering
● Flushing
● Malaise
● Fever
● Low BP
● Tachycardia
● Chest pain

15. References-
● Essentials of Medical Pharmacology by K.D. Tripathi.
● Image references- https://www.wikipedia.org/

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