Prostaglandins (PGs) and Leukotrienes (LTs) are biologically active derivatives of 20 carbon atom polyunsaturated essential fatty acids that are released from cell membrane phospholipids. They are the major lipid derived autacoids.

1. Prostaglandins, leukotrienes,
(Eicosanoids) and Platelet
activating factors
Dr. Chavan P. R.
Pharm D

2. Eicosanoids
• 20 carbon atom polyunsaturated essential fatty
acids
• Major lipid derived autacoids
• E.g. prostanoids - prostaglandins (PGs),
thromboxanes (Txs) ,leucotrienes (LTs),lipoxins.
• Main source - arachidonic acid

3. Eicosanoids synthesis, inhibition and
degradation

4. Prostaglandin receptors

5. Pharmacological actions
GIT:
• PGE2 and PGF2α cause contraction of the
longitudinal muscle of the gut while PGI2 and
PGF2α cause contraction of the circular muscle
of the gut.
• PGE2 relaxes the circular muscles.
• In general , large dose of PGs inhibits gastric
acid secretion.

6. Vascular smooth muscles :
• PGE2 and PGI2 cause vasodilatation , while
PGF2Α and TX cause vasoconstriction
Platelets :
• PGE1 and PGI2 inhibit platelets aggregation
while TX induces platelets aggregation.
Respiratory system:
• PGE1 , PGE2 AND PGI2 cause bronchi dilatation
while PGF2Α and TX cause bronchi constriction.

7. Renal system:
• PGE1, PGE2 and PGI2 increase GFR
(vasodilating effect ) and increase the Na
excretion , also enhance the release of renin.
• PGE2 is involved in renal phosphate excretion.
TX reduces renal function and GFR.
Reproductive system:
• PGE2 and PGF2α causes contraction of uterus ,
PGI2 increases penile erection.

8. CNS:
• Fever : PGE1 and PGE2 when are injected into
cerebral ventricles , they increase the body
temperature.
PGD2 when infused into cerebral ventricles
produces sleepiness .
• Neurotransmission: PG compounds inhibit the
release of Nor- adrenalin from post-ganglionic
sympathetic nerve endings.
• Neuro-endocrine: PG compounds promote the
secretion of prolactine , GH, TSH, ACTH, FSH
and LH.

9. Bone :
• PGD2 increases bone turnover (bone formation
and resorption) .
• PG is involved in bone loss in post-menopausal
women.
Eyes:
• PGF2α decreases intra-ocular pressure .

10. Uses
Reproductive indications:
• PGE2 and pgf2α when used in early pregnancy ,
• Cause abortion ,
• Terminate pregnancy at any stage ,
• Facilitates labor if given at time of labor.

11. Advantages of PG over Oxytocin:
• PGs are more safe in pregnant women with pre-
eclampsia , cardiac and renal diseases .
• PGs unlike Oxytocin, having no anti-diuretic
effect.
• PGE2 and PGF2α are involved in primary
dysmenorrhia.
• PGE1 is used in sexual dysfunction , injection of
PGE1 in cavernosa is important in management
of impotence in man.

12. CVS indications :
• PG compounds have anti-hypertensive effect due
to their vasodilating and natriuretic effects.
• PGI2 is used in pulmonary hypertension.
• PGE1 and PGI2 are used in Ryanaud disease.
Blood:
• PGI2 is very effective in preventing platelets
aggregation .

13. Respiratory indications:
• PGE2 is used as aerosol to relieve
bronchiospasm.
GIT indications :
• PGE1 analogue (Misoprostol)is cytoprotective
and used for treatment of gastric ulcer..
Eyes :
• PGF2α analogue is used in treatment of
glaucoma .

14. Immune indications:
• PGE2 and PGI2 inhibit T-cell proliferation and
clonal expansion by inhibiting interleukin I and
II.
• While TX and platelet activating factor
(PAF)stimulate T-cell proliferation and clonal
expansion by stimulating IL-I and II.

15. Side effects of PGs :
• GIT upset ,
• headache ,
• dizziness ,
• bronchiospasm ,
• allergic reactions ,
• syncope ,
• hypo or hypertension ,
• uterine laceration .

16. Leucotrienes Mechanism of action

17. Leucotriene receptors
• LTB4 (BLT1 and BLT2)
• cysteinyl LTs (LTC4, LTD4)
• cysLT1 (mainly expressed in bronchial and
intestinal muscle and has higher affinity for
LTD4 than for LTC4 ) and cysLT2 (leucocytes
and spleen)
• cysLT1 receptor antagonists - Montelukast,
Zafirlukast

18. Uses
• Abortion
• Induction/augmentation of labour
• Cervical priming (ripening)
• Postpartum haemorrhage (PPH)
• Peptic ulcer
• Glaucoma
• To maintain patency of ductus arteriosus
• To avoid platelet damage

19. PAF Synthesis & Degradation

20. Mechanism of action

21. PAF Actions
• Platelets - Aggregation and release reaction
• WBC - Potent chemotactic for neutrophils,
eosinophils and monocytes
• Blood vessels - Vasodilatation mediated by release
of EDRF occurs → fall in BP
- potent increase vascular permeability
• Visceral smooth muscle – bronchoconstrictor,
stimulates intestinal and uterine smooth muscle
• Stomach - contracts gastric smooth muscle.

22. PAF antagonists
• E.g. ginkgolide B (from a Chinese plant), and
some structural analogues of PAF.
• The PAF antagonists uses - treatment of stroke,
intermittent claudication, sepsis, myocardial
infarction, shock, g.i. ulceration, asthma and as
contraceptive.
• Alprazolam and triazolam antagonize some
actions of PAF.

23. Pathophysiological roles
• Inflammation
• Bronchial asthma
• Anaphylactic (and other) shock conditions
• Haemostasis and thrombosis
• Rupture of mature graafian follicle and
implantation
• Ischaemic states of brain, heart and g.i.t.,
including g.i. ulceration.

24. Thank you